Oral vitamin D3 supplementation increases serum fibroblast growth factor 23 concentration in vitamin D-deficient patients: a systematic review and meta-analysis.

Studies have suggested that vitamin D supplementation may increase serum fibroblast growth factor 23 (FGF23) among vitamin D-deficient patients although the results were inconsistent across the studies. This systematic review and meta-analysis was conducted to summarize all available data. A systematic review was conducted using MEDLINE and EMBASE database from inception to February 2019 to identify studies that provided oral vitamin D3 supplement to vitamin D-deficient participants (25-hydroxyvitamin D < 20 ng/mL). Mean serum FGF23 concentration and standard deviation of participants at baseline and after vitamin D3 supplementation were extracted to calculate standard mean difference (SMD). Pooled SMD was calculated by combining SMDs of each study using random effects model. Nine studies were eligible for the meta-analyses. Seven studies measured serum intact FGF23, and two studies measured serum C-terminal FGF23. The meta-analyses found that serum intact FGF23 increased significantly after oral vitamin D3 supplementation in vitamin D-deficient participants with the pooled SMD of 0.36 (95%CI, 0.14, 0.57; p = 0.001; I2 of 36%). Serum C-terminal FGF23 also increased after vitamin D3 supplementation in vitamin D-deficient participants with the pooled SMD of 0.28 although without reaching statistical significance (95%CI, - 0.08, 0.65; p = 0.13; I2 of 0%). Funnel plot of the meta-analysis of serum intact FGF23 did not provide a suggestive evidence for publication bias. Vitamin D supplementation leads to a significant increase in serum intact FGF23 among vitamin D-deficient patients. An increase in serum C-terminal FGF23 was also observed although the number of included studies was too small to demonstrate statistical significance. The present systematic review and meta-analysis revealed that serum intact FGF23 concentration increased significantly after oral vitamin D3 supplementation in vitamin D-deficient participants. An increase in serum C-terminal FGF23 concentration was also observed although the number of included studies was too small to demonstrate statistical significance.

Effect of vitamin D supplementation and ultraviolet B exposure on serum 25-hydroxyvitamin D concentrations in healthy volunteers: a randomized, crossover clinical trial.

BACKGROUND: Solar ultraviolet (UV) radiation during the summer and vitamin D supplementation are two major sources of vitamin D for humans at northern latitudes. However, little is known about the relative efficiency of these two vitamin D sources. OBJECTIVES: The main goal was to compare the efficiency of high-dose oral vitamin D3 supplementation (2000 IU per day for 30 days) with a simulated summer UV exposure [10 sunbed sessions to a total dose of 23·8 standard erythema doses (SED)] to improve vitamin D status. METHODS: Healthy volunteers were randomized into two groups: group 1 received vitamin D supplementation followed by 10 whole-body sunbed exposures; group 2 started with 10 sunbed exposures followed by vitamin D supplementation. RESULTS: The oral supplementation with vitamin D3 resulted in a mean (SEM) serum 25-hydroxyvitamin D [25(OH)D] increase of 25·3 (5·4) nmol L(-1) . A similar increase, 19·8 (5·4) nmol L(-1) , was observed after simulated summer UV exposure. At the end of the study, serum 25(OH)D concentrations were similar in both groups. CONCLUSIONS: Twice-weekly whole-body sunbed exposure to a dose of 4·8 SED is equal to 2000 IU daily of oral vitamin D supplementation for 30 days and enough to achieve and maintain serum 25(OH)D concentrations > 75 nmol L(-1) in ~55% of cases. Based on our calculations, this dose corresponds to a cumulative weekly whole-body exposure of 3·4 SED (~ 40 min around midday during the summer at the latitude of Oslo).

Umbilical cord plasma 25-hydroxyvitamin D concentration and immune function at birth: the Urban Environment and Childhood Asthma study.

BACKGROUND: Recent studies have reported conflicting data on the association between maternal intake of vitamin D during pregnancy and asthma. OBJECTIVE: To assess the influence of prenatal vitamin D status on immune function at birth. METHODS: In an inner-city birth cohort of 568 newborns, 520 of whom had at least one atopic parent, we measured the umbilical cord (UC) plasma concentration of 25-hydroxyvitamin D (25(OH)D) and the cytokine responses of UC blood mononuclear cells (UCMCs) to stimuli including phytohaemagglutinin (PHA), lipopolysaccharide (LPS), and peptidoglycan. In a subset, the UCMC expression of regulatory T cell markers and the suppressive activity of CD4(+) CD25(+) UCMCs were measured. Results The 25th, 50th, and 75th percentiles of UC plasma 25(OH)D level were 15.0, 20.2, and 25.6 ng/mL, respectively. Most cytokine responses of UCMC were not correlated with UC 25(OH)D concentration; however, IFN-γ release after LPS stimulation was weakly positively correlated with UC 25(OH)D concentration (r=0.11, P=0.01). PHA responses were not significantly correlated with 25(OH)D concentration. The UC plasma 25(OH)D concentration was inversely related to the number of CD25(+) (r=-0.20, P=0.06), CD25(Bright) (r=-0.21, P=0.05), and CD25(+) FoxP3 (r=-0.29, P=0.06) cells as a proportion of CD4(+) T cells in UC blood (r=-0.26, P=0.04) but not to the suppressive activity of CD4(+) CD25(+) cells (r=0.17, P=0.22). CONCLUSION AND CLINICAL RELEVANCE: UC 25(OH)D concentration was not correlated with most UCMC cytokine responses to multiple stimuli. There was a suggestion of a weakly positive correlation with IFN-γ release after LPS stimulation. The proportions of CD25(+) , CD25(Bright) , and CD25(+) FoxP3 cells to total CD4(+) T cells were inversely correlated with UC 25(OH)D concentration. Our findings suggest that higher vitamin D levels at birth may be associated with a lower number of T-regulatory cells. Vitamin D status in utero may influence immune regulation in early life.

Serum 25-hydroxyvitamin D and bone mineral density among Hispanic men.

UNLABELLED: There are few data on the skeletal health of Hispanic men. We observed differences in vitamin D deficiency and low BMD between Hispanic ethnic subgroups that persisted with adjustment for risk factors. Our data indicate a substantial burden of low BMD and vitamin D deficiency among Hispanic men. INTRODUCTION: Disparities within ethnic groups are generally ignored, but in evolving populations they may have implications for public health. We examined ethnic variation in serum 25-hydroxyvitamin D [25(OH)D] and bone mineral density (BMD) among Hispanic American men. METHODS: Three hundred and fifty-eight Hispanic males 30 to 79 years of age were studied. Logistic regression models assessed variation in odds of vitamin D deficiency (<20 ng/mL) and low BMD (T-score<-1) by ethnicity, with and without adjustment for risk factors (age, smoking, occupation, physical activity, body mass index, and sunlight exposure). RESULTS: Vitamin D deficiency was most common among Puerto Rican (26%), compared with Dominican (21%), Central American (11%), and South American (9%) men. Percentages with low BMD were: South American (44%), Puerto Rican (34%), Dominican (29%), and Central American (23%). Adjustment for age and risk factors failed to account for Hispanic subgroup differences in vitamin D deficiency and low BMD. Population estimates indicate a substantial burden of low BMD and vitamin D deficiency among Hispanic men. CONCLUSIONS: Our findings underscore the importance of examining the skeletal health of Hispanic subgroups, and suggest that a considerable number of Hispanic men may be at elevated risk of fracture and vitamin D deficiency.

5,6-Trans-25-hydroxycholecalciferol: vitamin D analog effective on intestine of anephric rats.

A new compound, 5,6-trans-25-hydroxycholecalciferol, has been synthesized and tested for its biological activity. Like 1,25-dihydroxycholecalciferol, it stimulates intestinal calcium transport in anephric rats, whereas 25-hydroxycholecalciferol does not. But this analog has little if any activity in stimulating mobilization of calcium from the bone of anephric rats.

1,25-dihydroxycholecalciferol: metabolite of vitamin D3 active on bone in anephric rats.

Nephrectomy prevents completely the bone calcium mobilization response to 25-hydroxycholecalciferol. In contrast it does not prevent this response to 1,25-dihydroxycholecalciferol. Because it is known that the kidney is the site of 1,25-dihydroxycholecalciferol formation, these results provide evidence that 1,25-dihydroxycholecalciferol or a further metabolite thereof and not 25-hydroxycholecalciferol is the metabolically active form of vitamin D(3) responsible for bone calcium mobilization.

Regulation of cutaneous previtamin D3 photosynthesis in man: skin pigment is not an essential regulator.

When human skin was exposed to simulated solar ultraviolet radiation, epidermal 7-dehydrocholesterol was converted to previtamin D3. During prolonged exposure to simulated solar ultraviolet radiation, the synthesis of previtamin D3 reached a plateau at about 10 to 15 percent of the original 7-dehydrocholesterol content, and previtamin D3 was photoisomerized to two biologically inert isomers, lumisterol3 and tachysterol3. Increases either in skin melanin concentration or in latitude necessitated increases in the exposure time to simulated solar ultraviolet radiation required to maximize the formation, but not the total content, of previtamin D3. In order of importance, the significant determinants limiting the cutaneous production of previtamin D3 are (i) photochemical regulation, (ii) pigmentation, and (iii) latitude.

Side chain metabolism of 25-hydroxy-[26,27-14C] vitamin D3 and 1,25-dihydroxy-[26,27-14C] vitamin D3 in vivo.

Radioactive CO2 was detected in expired air after the administration of 25-hydroxy-[26,27-14C] vitamin d3 to vitamin D-deficient hypocalcemic rats; 14co2 was also detected after the administration of 1,25-dihydroxy-[26,27-14C] vitamin D3 to rats raised on the same diet. Nephretcomy totally abolished 14CO2 formation after administration of 25-hydroxy-[26,27-14C] vitamin D3 but not after the administration of 1,25-dihydroxy-[26,27-14C] vitamin D3. The production of 14CO2 commenced within 4 hours after injection of 1,25-dihydroxy-[26,27-14C] vitamin D3, suggesting a possible relevance of this reaction to the function of 1,25-dihydroxyvitamin D3. These results at least demonstrate a new metabolic pathway of vitamin D3 metabolism involving the oxidation of a portion of the side chain of 1,25-dihydroxyvitamin D3 to CO2.

A parathyroid hormone inhibitor in vivo: design and biological evaluation of a hormone analog.

A synthetic analog of bovine parathyroid hormone (bPTH), [tyrosine-34] bPTH-(7-34)NH2, was found to inhibit parathyroid hormone action in vivo. When the analog and parathyroid hormone were infused simultaneously to rats at a molar ratio of 200 to 1, the analog inhibited the excretion of urinary phosphate and adenosine 3',5'-monophosphate. When infused alone at the same dose rate, the analog was devoid of agonist activity. The compound was prepared by following design principles developed for inhibitors of parathyroid hormone, and is believed to be the first antagonist of parathyroid hormone that is effective in vivo.

Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin.

The photosynthesis of previtamin D3 from 7-dehydrocholesterol in human skin was determined after exposure to narrow-band radiation or simulated solar radiation. The optimum wavelengths for the production of previtamin D3 were determined to be between 295 and 300 nanometers. When human skin was exposed to 295-nanometer radiation, up to 65 percent of the original 7-dehydrocholesterol content was converted to previtamin D3. In comparison, when adjacent skin was exposed to simulated solar radiation, the maximum formation of previtamin D3 was about 20 percent. Major differences in the formation of lumisterol3, and tachysterol3 from previtamin D3 were also observed. It is concluded that the spectral character of natural sunlight has a profound effect on the photochemistry of 7-dehydrocholesterol in human skin.

1 -Hydroxy derivative of vitamin D 3 : a highly potent analog of 1 ,25-dihydroxyvitamin D 3 .

The 1alpha-hydroxy derivative of vitamin D(3) has been chemically synthesized and tested for its biological activity. This analog has comparable biological activity on a weight basis to 1,25-dihydroxyvitamin D(3) in the stimulation of intestinal calcium transport and bone calcium mobilization in normnal and anephric rats. Because the 1alpha-hydroxy derivative is synthesized from cholesterol, it is easier and less expensive to prepare than 1alpha,25-dihydroxy derivative, making it attractive as a drug in the treatment of renal osteodystrophy and hypopara-thyroidism.

1,25-dihydroxycholecalciferol: a potent stimulator of bone resorption in tissue culture.

1,25-Dihydroxycholecalciferol (DHCC), isolated from kidney homogenates incubated with 25-hydroxycholecalciferol (HCC), stimulated the release of previously incorporated (45)45Ca from fetal rat bones in organ culture, at concentrations of 10(-10) to 10(-8)M. The dose response curves for 1,25-DHCC and 25-HCC, the parent compound, are parallel, but 1,25-DHCC is about 100 times as potent on a weight basis. Brief exposure to maximum doses of either agent leads to prolonged bone resorption.

Isotachysterol-3 and 25-hydroxyisotachysterol-3: analogs of 1,25-dihydrox vitamin D3.

Isotachysterol(3), 25-hydroxyisotachysterol(3), and isovitamin D(3) have been synthesized and tested for biological activity. Like 1,25-dihydroxyvitamin D(3), isotachysterol(3) stimulates intestinal calcium transport and bone calcium mobilization in anephric rats, whereas 25-hydroxyvitamin D(3) does not. Although isovitamin D(3) is biologically active in normal rats it is inactive in anephric rats.

Synthesis of (6-3H)-1alpha-hydroxyvitamin D3 and its metabolism in vivo to (3H)-1alpha,25-dihydroxyvitamin D3.

[6-3H]-1alpha-Hydroxyvitamin D3 was chemically synthesized and its full biological activity and radiochemical purity were demonstrated. With the use of this preparation it has been possible to demonstrate in vivo that in rats the [6-3H]-1Alpha-hydroxyvitamin D3 is converted to [6-3H]-1alpha,25-dihydroxyvitamin D3, the natural hormone. In fact, in the intestine and bone of rats given 32 picomoles of [6-3H]-1alpha-hydroxyvitamin D3 each day for 6 days, more than 80 percent of the lipid-soluble radioactivity exists as [6-3H]-1alpha,25-dihydroxyvitamin D3, a finding that suggests that much of the biological effectiveness of 1alpha-hydroxyvitamin D3 is due to its conversion to 1alpha,25-dihydroxyvitamin D3.

Photosynthesis of previtamin D3 in human skin and the physiologic consequences.

Photosynthesis of previtamin D3 can occur throughout the epidermis in the dermis when hypopigmented Caucasian skin is exposed to solar ultraviolet radiation. Once previtamin D3 is formed in the skin, it undergoes a temperature-dependent thermal isomerization that takes at least 3 days to complete. The vitamin D-binding protein preferentially translocates the thermal product, vitamin D3, into the circulation. These processes suggest a unique mechanism for the synthesis, storage, and slow, steady release of vitamin D3 from the skin into the circulation.

Gender- and compartment-specific bone loss in C57BL/6J mice: correlation to season?

Seasonal variation in bone mineral density (BMD) has been documented in humans, and has been attributed to changes in 25-hydroxyvitamin D [25(OH)D] synthesis. To test the hypothesis that seasonal changes in bone mass occur in laboratory mice, we measured body composition, femoral bone phenotypes, and serum bone markers in 16-wk-old male and female C57BL/6 (B6) mice during the summer (June-August) and winter (December-February) months at The Jackson Laboratory in Bar Harbor, Maine. Both male and female B6 mice had higher volumetric BMD in the summer than winter. Females showed reduced trabecular bone, whereas males showed changes in bone volume. Males, but not females, had higher insulin-like growth factor 1 in summer than in winter, and only males showed an increase in body weight during the winter. No seasonal differences in serum TRAP5b, osteocalcin, or 25(OH)D were noted for either sex. We conclude that seasonal variation in skeletal and body composition parameters in B6 mice is significant and must be considered when performing longitudinal phenotyping of the skeleton. Further studies are needed to determine the environmental factors that cue seasonal changes in body composition and the mechanisms that produce these changes.

Aging decreases the capacity of human skin to produce vitamin D3.

An evaluation of surgically obtained skin (age range, 8-92 yr) revealed that there is an age-dependent decrease in the epidermal concentrations of provitamin D3 (7-dehydrocholesterol). To ascertain that aging indeed decreased the capacity of human skin to produce vitamin D3, some of the skin samples were exposed to ultraviolet radiation and the content of previtamin D3 was determined in the epidermis and dermis. The epidermis in the young and older subjects was the major site for the formation of previtamin D3, accounting for greater than 80% of the total previtamin D3 that was produced in the skin. A comparison of the amount of previtamin D3 produced in the skin from the 8- and 18-yr-old subjects with the amount produced in the skin from the 77- and 82-yr-old subjects revealed that aging can decrease by greater than twofold the capacity of the skin to produce previtamin D3. Recognition of this difference may be extremely important for the elderly, who infrequently expose a small area of skin to sunlight and who depend on this exposure for their vitamin D nutritional needs.