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)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<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)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.

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.

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.

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.

Differences among total and in vitro digestible phosphorus content of plant foods and beverages.

OBJECTIVE: Among plant foods, grain products, legumes, and seeds are important sources of phosphorus (P). Current data on P content and absorbability of P from these foods are lacking. Measurement of in vitro digestible P (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected foods and to compare the amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP content of 21 foods and drinks of plant origin were measured by inductively coupled plasma optical emission spectrometry. In DP analysis, samples were digested enzymatically in principle in the same way as in the alimentary canal before P analyses. The most popular national brands were chosen for analysis. RESULTS: The highest amount of TP (667 mg/100 g) was found in sesame seeds with hull, which also had the lowest percentage of DP (6%) to TP. Instead, in cola drinks and beer, the percentage of DP to TP was 87 to 100% (13 to 22 mg/100 g). In cereal products, the highest TP content (216 mg/100 g) and DP proportion (100%) were present in industrial muffins, which contain sodium phosphate as a leavening agent. Legumes contained an average DP content of 83 mg/100 g (38% of TP). CONCLUSION: Absorbability of P may differ substantially among different plant foods. Despite high TP content, legumes may be a relatively poor P source. In foods containing phosphate additives, the proportion of DP is high, which supports previous conclusions of the effective absorbability of P from P additives.

Differences among total and in vitro digestible phosphorus content of meat and milk products.

OBJECTIVE: Meat and milk products are important sources of dietary phosphorus (P) and protein. The use of P additives is common both in processed cheese and meat products. Measurement of in vitro digestible phosphorus (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected meat and milk products and to compare amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP contents of 21 meat and milk products were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). In DP analysis, samples were digested enzymatically, in principle, in the same way as in the alimentary canal before the analyses. The most popular national brands of meat and milk products were chosen for analysis. RESULTS: The highest TP and DP contents were found in processed and hard cheeses; the lowest, in milk and cottage cheese. TP and DP contents in sausages and cold cuts were lower than those in cheeses. Chicken, pork, beef, and rainbow trout contained similar amounts of TP, but slightly more variation was found in their DP contents. CONCLUSIONS: Foods containing P additives have a high content of DP. Our study confirms that cottage cheese and unenhanced meats are better choices than processed or hard cheeses, sausages, and cold cuts for chronic kidney disease patients, based on their lower P-to-protein ratios and sodium contents. The results support previous findings of better P absorbability in foods of animal origin than in, for example, legumes.

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.

Wintertime vitamin D supplementation inhibits seasonal variation of calcitropic hormones and maintains bone turnover in healthy men.

Vitamin D is suggested to have a role in the coupling of bone resorption and formation. Compared with women, men are believed to have more stable bone remodeling, and thus, are considered less susceptible to the seasonal variation of calcitropic hormones. We examined whether seasonal variation exists in calcitropic hormones, bone remodeling markers, and BMD in healthy men. Furthermore, we determined which vitamin D intake is required to prevent this variation. Subjects (N = 48) were healthy white men 21-49 yr of age from the Helsinki area with a mean habitual dietary intake of vitamin D of 6.6 +/- 5.1 (SD) microg/d. This was a 6-mo double-blinded vitamin D intervention study, in which subjects were allocated to three groups of 20 microg (800 IU), 10 microg (400 IU), or placebo. Fasting blood samplings were collected six times for analyses of serum (S-)25(OH)D, iPTH, bone-specific alkaline phosphatase (BALP), and TRACP. Radial volumetric BMD (vBMD) was measured at the beginning and end of the study with pQCT. Wintertime variation was noted in S-25(OH)D, S-PTH, and S-TRACP (p < 0.001, p = 0.012, and p < 0.05, respectively) but not in S-BALP or vBMD in the placebo group. Supplementation inhibited the winter elevation of PTH (p = 0.035), decreased the S-BALP concentration (p < 0.05), but benefited cortical BMD (p = 0.09) only slightly. Healthy men are exposed to wintertime decrease in vitamin D status that impacts PTH concentration. Vitamin D supplementation improved vitamin D status and inhibited the winter elevation of PTH and also decreased BALP concentration. The ratio of TRACP to BALP shows the coupling of bone remodeling in a robust way. A stable ratio was observed among those retaining a stable PTH throughout the study. A daily intake of vitamin D in the range of 17.5-20 microg (700-800 IU) seems to be required to prevent winter seasonal increases in PTH and maintain stable bone turnover in young, healthy white men.

Effects of fatty and lean fish intake on blood pressure in subjects with coronary heart disease using multiple medications.

BACKGROUND: Intake of fish and long-chain n-3 fatty acids has been of wide interest due to their beneficial effects on cardiovascular risk factors and lower coronary heart disease (CHD) risk. AIM OF THE STUDY: The aim of this pilot study was to examine the effects of fatty fish and lean (white) fish on fatty acid composition of serum lipids and cardiovascular risk factors in subjects with CHD using multiple drugs for this condition. METHODS: The study was an 8-week controlled, parallel intervention. Inclusion criteria were myocardial infarction or unstable ischemic attack, age under 70 years, use of betablockers and presence of sinus rhythm. The subjects were randomized to one of the following groups: 4 meals/week fatty fish (n = 11), 4 meals/week lean fish (n = 12) and control diet including lean meat (n = 10). RESULTS: The mean (+/-SD) of reported fish meals per week was 4.3 +/- 0.4, 4.7 +/- 1.1 and 0.6 +/- 0.4 in the groups, respectively. The proportions of eicosapentaenoic and docosahexaenoic acids in serum lipids increased in the fatty fish group only (P < 0.05). Systolic and diastolic blood pressure levels decreased in the lean fish group (0 vs. 8 week: 3.5 +/- 3.2 and 4.6 +/- 3.6%, respectively, P < 0.05). Serum total triglyceride concentration did not significantly change. HDL cholesterol concentration change differed among groups but without significant post hoc differences. Apolipoprotein A-1 concentration decreased in the control group (0 vs. 8 week, P < 0.05). Coagulation factors, 25-hydroxy vitamin D, and heart rate variability (24 h Holter) did not change among the groups. CONCLUSIONS: Our results suggest that intake of lean fish at least four times per week could reduce blood pressure levels in CHD patients.

Vitamin D deficiency and low bone status in adult female garment factory workers in Bangladesh.

The manufacture of garments is the main industry in Bangladesh and employs 1.6 million female workers. Due to the indoor lifestyle and low dietary intake of calcium, we hypothesised that they are at risk of low vitamin D and bone mineral status. Two hundred female garment workers (aged 18-36 years) were randomly selected. Serum 25-hydroxyvitamin D (S-25OHD), serum intact parathyroid hormone (S-iPTH), serum calcium (S-Ca), serum phosphate (S-P) concentration and serum alkaline phosphatase activity (S-ALP) were measured from fasting samples. Bone indexes of hip and spine were measured by dual-energy X-ray absorptiometry. The mean S-25OHD (36.7 nmol/l) was low compared to that recommended for vitamin D sufficiency. About 16% of the subjects were found to be vitamin D-deficient (S-25OHD 21 ng/l) was associated with progressive reduction in bone mineral density at the femoral neck and lumbar spine. According to the WHO criteria, the mean T-score of the femoral neck and lumbar spine of the subjects were within osteopenic range. We observed that subjects with a bone mineral density T-score < -2.5 had a trend of lower values of BMI, waist-hip circumference, mid-upper-arm circumference, S-25OHD and higher S-iPTH and S-ALP. The high prevalence of hypovitaminosis D and low bone mineral density among these subjects are indicative of higher risk for osteomalacia or osteoporosis and fracture.

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.