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The phosphaturic hormone fibroblast growth factor 23 (FGF23) is a risk marker of cardiovascular and all-cause mortality. We therefore aimed to synthesize the evidence for the effect of vitamin D administration on circulating FGF23 concentrations. We performed a systematic review and meta-analysis of randomized, placebo-controlled trials (RCTs) in several databases from inception to January 2020. A total of 73 records were identified for full-text review, and 21 articles with 23 studies were included in the final analysis. The selected studies included 1925 participants with 8-156 weeks of follow-up. The weighted mean difference in FGF23 in the vitamin D versus placebo group was +21 pg/ml (95% CI: 13-28 pg/ml; P < 0.001) with considerable heterogeneity among studies (I 2  = 99%). The FGF23 increment was higher in patients with end-stage kidney/heart failure than in other individuals (+300 pg/ml [95% CI: 41-558 pg/ml] vs. +20 pg/ml [95% CI: 12-28 pg/ml], P interaction  = 0.03), and if baseline 25-hydroxyvitamin D concentrations were <50 nmol/l instead of ≥50 nmol/l (+34 pg/ml [95% CI: 18-51 pg/ml] vs. +9 pg/ml [95% CI: 3-14 pg/ml]; P interaction  = 0.002). Moreover, the FGF23 increment was influenced by vitamin D dose/type (vitamin D dose equivalent ≤ 2000 IU/day: +2 pg/ml [95% CI: 0-3 pg/ml]; vitamin D dose equivalent > 2000 IU/day: +18 pg/ml [95% CI: 6-30 pg/ml]; administration of activated vitamin D: +67 pg/ml [95% CI: 16-117 pg/ml]; P interaction  = 0.001). Results were not significantly influenced by study duration (P interaction  = 0.14), age class (P interaction  = 0.09), or assay provider (P interaction  = 0.11). In conclusion, this meta-analysis of RCTs demonstrates that vitamin D administration of >2000 IU/d vitamin D or activated vitamin D significantly increased concentrations of the cardiovascular risk marker FGF23, especially in patients with end-stage kidney/heart failure.

Objectives: To clarify the potential role of vitamin D supplementation on bone metabolism in congestive heart failure (CHF) patients with low vitamin D status and insufficient dietary calcium intake., Subjects/methods: One hundred and two ambulatory male CHF patients were recruited, of whom the majority was treated with loop diuretics. Nine patients died during follow-up. Additional 14 participants dropped out prematurely because their health status worsened markedly. Five patients had to be excluded due to lack of compliance. A daily vitamin D3 supplement plus 500 mg calcium (CaD group) or a placebo plus 500 mg calcium (Ca group) was given for 9 months. Biochemical parameters of vitamin D and bone metabolism were analyzed at baseline and after 9 months., Results: Median 25-hydroxyvitamin D concentrations increased from 41.7 to 103.0 nmol/l (P < 0.001) in the CaD group and remained constant in the Ca group, while median calcium intake increased above 1200 mg/day in both groups. The percentage of patients with elevated parathyroid hormone levels (> 60 pg/ml), as well as the serum concentration of undercarboxylated osteocalcin, an indicator of osteoporotic fracture risk and the bone resorption marker C-telopeptide fell significantly in both study groups (P < 0.025-0.001). At the end of the study period, biomarkers of bone turnover did not differ between groups., Conclusions: A vitamin D3 supplement of 50 microg/day has no additional beneficial effects on markers of bone metabolism in CHF patients with low initial 25-hydroxyvitamin D concentrations if an adequate daily calcium intake is guaranteed.

Objective: We investigated whether ingestion of polyphenols from fruit juices or a fruit-vegetable-concentrate affects lymphocyte proliferation and apoptosis in human immunodeficiency virus (HIV)-seropositive (HIV(+)) and HIV-seronegative (HIV(-)) subjects., Design: Randomized, prospective pilot intervention study., Setting: University of Bonn, Department of General Internal Medicine., Subjects: A total of 23 HIV(+) subjects from the HIV outpatient clinic, 18 HIV(-) controls., Interventions: Subjects ingested either 1 l of fruit juice or 30 ml of fruit-vegetable-concentrate daily for 16 weeks in addition to their regular diet. Lymphocyte proliferation and apoptosis were investigated in peripheral blood mononuclear cells at baseline, during 16-weeks of intervention, and after a 6-week washout. Proliferation was assessed by (3)H-thymidine incorporation and apoptosis by nuclear content as measured by flow cytometry., Results: Supplementation of fruit juices increased phytohemagglutinin-induced lymphocyte proliferation (mitotic index) in HIV(+) patients from 18+/-16 to 40+/-34 (P=0.004) and in healthy controls from 27+/-16 to 51+/-21 (P=0.016). Apoptosis was not affected in HIV(+) patients, but rose in healthy controls from 9+/-10 to 34+/-11 (apoptotic index; P=0.001). Intervention with concentrate did not significantly alter proliferation and apoptosis in HIV(+) and HIV(-) subjects., Conclusions: Even though apoptosis did not change in HIV(+) subjects, ingestion of polyphenol-rich fruit juices might be favorable to HIV(+) patients due to enhanced proliferation, which could restore disturbances in T-cell homeostasis. In healthy controls, increased lymphocyte proliferation during juice consumption was counterbalanced by increased apoptosis.

Objective: To characterize the influence of body mass index (BMI), body composition, hormonal factors and disease duration on bone metabolism markers in anorexia nervosa (AN) patients., Design: Case-control study with 51 AN patients and 51 controls matched for age, sex and body height. Assessment of anthropometric and bioimpedance data, and of biochemical serum parameters and of oral contraceptives use., Results: Patients had a lower BMI, lower fat mass, lower fat-free mass and lower muscle mass (MM) compared to the controls (all P values <0.001). Moreover, serum levels of osteocalcin (bone formation marker) were lower while serum C-telopeptide concentrations (CTx; bone resorption marker) and the CTx/osteocalcin ratio (an index reflecting the balance of bone remodeling) were higher in the AN patients compared to the controls (P<0.01-0.001). In addition, patients had enhanced serum calcium and cortisol levels and reduced serum levels of thyroid hormones, insulin, and leptin (P values <0.05-0.001). Mean disease duration was 91+/-13 months. In a multiple regression analysis, BMI (P<0.0001), MM (P<0.005) and duration of the disease (P<0.005) were independent predictors of the CTx/osteocalcin ratio in the AN patients. There was a nonlinear association between BMI and the CTx/osteocalcin ratio of r=-0.72 (P<0.001) in the AN patients, but only a weak relation of r=-0.27 (P<0.05) between these parameters in the control subjects. Use of oral contraceptives had no effect on the CTx/osteocalcin ratio, neither in AN patients nor in controls., Conclusions: Data indicate an uncoupling of bone formation and bone resorption in AN, which is primarily the result of a low BMI and influenced by the duration of the disease.