Influence of food matrix delivery system on the bioavailability of vitamin D3: A randomized crossover trial in postmenopausal women.

OBJECTIVES: Vitamin D insufficiency (blood 25-hydroxyvitamin D <50 nmol/L) is a global health problem. Vitamin D food fortification might be a solution, but knowledge is sparse on which food matrices yield the highest bioavailability. The aim of this study was to investigate the influence of different food matrices including complex formations with whey proteins on the human bioavailability of vitamin D. METHODS: In this randomized, multiple crossover trial, we enrolled 30 postmenopausal women 60 to 80 y of age with vitamin D insufficiency. We measured changes in serum concentrations of vitamin D3 (D3) postprandially for 24 h in response to the intake of 500 mL of different food matrices with 200 µg D3 added compared with a control (500 mL of water). Foods included apple juice with whey protein isolate (WPI), apple juice, semi-skim milk, and water (with D3). The food matrices were provided in a randomized order with ≥10-d washout period between them. On each intervention day, blood samples were collected at 0, 2, 4, 6, 8, 10, 12 and 24 h. RESULTS: D3 with WPI in juice did not enhance area under the curve (AUC) of serum D3 compared with juice without WPI (370 nmol ×  24 h/L; 95% confidence interval [CI], 321-419 versus 357 nmol ×  24 h/L; 95% CI, 308-406 nmol ×  24 h/L; P = 0.65). However, compared with juice, the AUC was significantly higher in response to the intake of D3 in milk (452 nmol ×  24 h/L; 95% CI, 402-502 nmol ×  24 h/L) and water with D3 (479 nmol ×  24 h/L; 95% CI, 430-527 nmol ×  24 h/L; P < 0.05). No difference was observed between milk and water (P = 0.34). CONCLUSIONS: The bioavailability of D3 was superior in milk and water compared with juice, regardless of whether WPI was added.

The Diurnal Blood Metabolome and Effects of Vitamin D Supplementation: A Randomised Crossover Trial in Postmenopausal Women.

A way to maintain an adequate vitamin D status is through supplementation. Demonstration of blood-metabolome rhythmicity of vitamin D3 post-dosing effects is lacking in the pharmaco-metabonomics area. Thus, the overall aim of this study was to investigate the diurnal changes in the blood metabolome and how these are affected by vitamin D3 supplementation. The study was conducted as a crossover study, and the treatment included 200 µg (8000 IU) of vitamin D3 as compared with placebo with a washout period of at least 10 days. The participants were postmenopausal women aged 60−80 years (N = 29) with vitamin D insufficiency (serum 25-hydroxyvitamin D < 50 nmol/L) but otherwise healthy. During the intervention day, blood samples were taken at 0 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, and 24 h, and plasma was analysed by proton nuclear magnetic resonance (NMR) spectroscopy as a metabolomics approach. In general, diurnal effects were identified for the majority of the 20 quantified metabolites, and hierarchical cluster analysis revealed a change in the overall plasma metabolome around 12 AM (6 h after intervention), suggesting that the diurnal rhythm is reflected in two diurnal plasma metabolomes; a morning metabolome (8−12 AM) and an afternoon/evening metabolome (2−8 PM). Overall, the effect of vitamin D supplementation on the blood metabolome was minor, with no effect on the diurnal rhythm. However, a significant effect of the vitamin D supplementation on plasma acetone levels was identified. Collectively, our findings reveal an influence of diurnal rhythm on the plasma metabolome, while vitamin D supplementation appears to have minor influence on fluctuations in the plasma metabolome.

The acute effects of milk intake on calcium homeostasis and cardiovascular outcome: A randomized crossover trial in postmenopausal women.

OBJECTIVE: The importance of calcium intake from dairy in regard to cardiovascular health has been investigated in several studies with discrepant results. Hence, we aim to investigate the immediate effects of milk intake on cardiovascular function. DESIGN: A randomized crossover study with at least 10 days for washout between the two interventions, 500 ml of water with 200 µg of cholecalciferol or 500 ml of semi-skimmed milk containing approximately 600 mg of calcium with 200 µg of cholecalciferol. PATIENTS: Twenty community-based postmenopausal women aged 60-80 years. MEASUREMENTS: Parathyroid hormone and ionized calcium were measured at baseline and after 2 and 4 h on each study day. Pulse wave analysis and velocity were measured at baseline and after 4 h on each study day. RESULTS: Compared to water, milk intake increased ionized calcium levels by 0.02 mmol/L (p = .029) and decreased parathyroid hormone levels by 1.78 pmol/L (p < .001). The two interventions caused no changes as measured 4 h after the intervention in the following indices of cardiovascular health; pulse wave velocity, brachial diastolic or systolic blood pressure, central diastolic or systolic blood pressure, mean arterial pressure, pulse pressure, augmentation pressure, augmentation index, heart rate or pulse transit time. CONCLUSIONS: Despite significant changes in calcium homeostasis with increased levels of ionized calcium following milk intake, no acute effects seem to occur on measures of cardiovascular health.

3-Hydroxybutyrate administration elevates plasma parathyroid hormone in a pilot human randomized, controlled, cross over trial.

CONTENT: Ketone bodies, in particular 3-hydroxybutyrate (3OHB), are known to possess important energetic and signaling capacities. There is a growing block of evidence, that ketogenic dieting (KD), fasting, and sodium glucose transporter 2 inhibitor (SGLT2i) treatment are associated with hyperparathyroidism and negative bone health. OBJECTIVE: We aimed to study the effect of exogenous 3OHB administration on bone metabolism, specifically the effect on parathyroid hormone (PTH) and calcium/phosphate homeostasis. DESIGN: A randomized, controlled, cross over study with two arms: i) saline infusion and ii) 3OHB infusion. SETTING: The study was conducted at Aarhus University Hospital. PARTICIPANTS: We examined eight healthy human subjects aged 50-70 years. INTERVENTION: Continuous intravenous DL-3OHB-NaCl infusion or 0.9% NaCl was administered for 390 min. MAIN OUTCOME MEASURES: The study was designed to test the impact of 3OHB on PTH, calcium-phosphate, C-terminal Telopeptide (CTX), and Procollagen I N-terminal Propeptide (PINP). The study was a post hoc study. RESULTS: The PTH concentration increased by 25% with a concomitant drop in phosphate of 30% in the 3OHB group. 3OHB infusion increased concentrations of CTX by 5%, without changes in PINP and albumin corrected calcium concentrations. CONCLUSION: In conclusion, 3OHB administration increases PTH concentration and markers of bone resorption. These findings suggest a possible negative effect on bone health, which needs to be determined in future studies.

Bone Health in Patients with Type 2 Diabetes Treated by Roux-En-Y Gastric Bypass and the Role of Diabetes Remission.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) has been associated with negative effects on bone. Whether this association is affected by pre-surgical type 2 diabetes (T2D) and surgically induced diabetes remission is unknown. METHODS: In this cross-sectional, matched cohort study 6 years after RYGB, we investigated bone health in 96 individuals with body mass index (BMI) > 35 kg/m2 and T2D (stratified on current diabetes status) treated by RYGB 6 years earlier compared with 49 non-operated individuals with T2D matched with respect to sex, age, and current BMI. Main outcome measures were areal and volumetric bone mineral density (aBMD and vBMD), bone turnover, and odds ratio of osteoporosis/osteopenia. RESULTS: The RYGB group had lower hip (0.916 vs 1.010 g/cm2, p < 0.001), forearm (0.497 g/cm2 vs 0.554 g/cm2, p < 0.001) aBMD, (269.63 mg/cm3 vs 306.07 mg/cm3, p < 0.001) tibial, and radial (238.57 mg/cm3 vs 278.14 mg/cm3, p < 0.0001) vBMD than the control group. Relative to the control group, c-terminal cross-linked telopeptide, procollagen type I amino-terminal propeptide, and osteocalcin were 75%, 41%, and 72% higher in the RYGB group, respectively (all p < 0.001). Odds ratio for osteopenia/osteoporosis in operated individuals was 2.21 (95% CI 1.06; 4.79, p = 0.05). Overall, stratified analysis on current diabetes status did not alter these outcomes. CONCLUSIONS: Individuals with T2D treated by RYGB, compared to individuals with T2D of similar age and body composition not treated by RYGB, have lower BMD, lower bone strength, and increased levels of several bone turnover markers. Bone health was not associated with current diabetes status in the RYGB group.

Effect of calcium citrate vs calcium carbonate on elevated parathyroid hormone after Roux-en-Y gastric bypass. A double-blinded, randomized trial.

OBJECTIVE: Following Roux-en-Y gastric bypass (RYGB), elevated parathyroid hormone (PTH) levels potentially harmful to bone health are commonly observed. Owing to assumed superior absorption, calcium citrate is often recommended over calcium carbonate following RYGB for the treatment of elevated PTH. We aimed to investigate the impact of either calcium carbonate or calcium citrate (1200 mg elementary calcium) in patients with elevated PTH levels following RYGB. DESIGN: Clinical, double-blinded, randomized controlled trial of a 12-week duration at a Danish University Hospital. PATIENTS AND MEASUREMENTS: Thirty-nine (no drop out) RYGB operated patients with elevated PTH levels (PTH > 6.9 pmol/L) and normal plasma levels of calcium and 25-hydroxyvitamin D were randomized to either calcium carbonate or calcium citrate (1200 mg elementary calcium/daily). We assessed change in PTH as the primary outcome. RESULTS: The effect of the two calcium formulations on change in PTH was comparable and neutral: -1.9% (calcium citrate) vs +0.9% (calcium carbonate), P = 0.680. Compared to the carbonate-treated group, the following bone turnover markers decreased significantly in the citrate-treated group: procollagen I N-terminal propeptide (-16.6% vs -3.2%, P = 0.021), osteocalcin (-17.2% vs -4.3%, P = 0.007) and bone-specific alkaline phosphatase (-5.9% vs 3.7%, P = 0.027) and remained significantly decreased after multivariable adjustment. CONCLUSION: Increasing the dose of calcium supplementation in RYGB operated patients with slightly elevated PTH levels does not normalize PTH levels, regardless of the type of supplement. Our results do not support recommending supplementation with calcium citrate over calcium carbonate in RYGB patients.

The Impact of Diagnosis on Job Retention: A Danish Registry-Based Cohort Study.

Background. In 1998, Denmark introduced the flex job scheme to ensure employment of people with a permanent reduced work capacity. This study investigated the association between select diagnoses and the risk of disability pension among persons eligible for the scheme. Methods. Using the national DREAM database we identified all persons eligible for the flex job scheme from 2001 to 2008. This information piece was linked to the hospital discharge registry. Selected participants were followed for 5 years. Results. From the 72,629 persons identified, our study included 329 patients with rheumatoid arthritis, 10,120 patients with spine disorders, 2179 patients with ischemic heart disease, and 1765 patients with functional disorders. A reduced risk of disability pension was found in the group with rheumatoid arthritis (hazard ratio = 0.69 (0.53-0.90)) compared to the group with spine disorders. No differences were found when comparing ischemic heart disease and functional disorders. Employment during the first 3 months of the flex job scheme increased the degree of employment for all groups. Conclusion. Differences in the risk of disability pension were identified only in patients with rheumatoid arthritis. This study demonstrates the importance of obtaining employment immediately after allocation to the flex job scheme, regardless of diagnosis.