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1.
Mol Ecol ; 31(18): 4607-4621, 2022 09.
Article in English | MEDLINE | ID: mdl-34888965

ABSTRACT

Vitamin D has a well-established role in skeletal health and is increasingly linked to chronic disease and mortality in humans and companion animals. Despite the clear significance of vitamin D for health and obvious implications for fitness under natural conditions, no longitudinal study has tested whether the circulating concentration of vitamin D is under natural selection in the wild. Here, we show that concentrations of dietary-derived vitamin D2 and endogenously produced vitamin D3  metabolites are heritable and largely polygenic in a wild population of Soay sheep (Ovis aries). Vitamin D2  status was positively associated with female adult survival, and vitamin D3  status predicted female fecundity in particular, good environment years when sheep density and competition for resources was low. Our study provides evidence that vitamin D status has the potential to respond to selection, and also provides new insights into how vitamin D metabolism is associated with fitness in the wild.


Subject(s)
Ergocalciferols , Vitamin D , Adult , Animals , Cholecalciferol , Female , Humans , Sheep
2.
Matern Child Nutr ; 14(1)2018 01.
Article in English | MEDLINE | ID: mdl-28421711

ABSTRACT

The prevalence of vitamin D deficiency in pregnant white-skinned women (WSW) and their infants has not been investigated at northern latitudes in a developed county. A 2-year observational cohort study was undertaken in the North West of England to determine 25-hydroxyvitamin D (25OHD) levels in WSW and their infants during pregnancy and 4 months postdelivery and to explore factors associated with these levels. Nutritional and lifestyle questionnaires were completed and 25OHD levels measured at 28 weeks and 4 months postdelivery. Twenty-seven percent and 7% of WSW had insufficient and deficient levels of 25OHD during pregnancy and 48% and 11% four months postdelivery. WSW with Fitzpatrick skin-type I (FST I) have significantly lower 25OHD than other skin types after controlling for time spent outside and vitamin D intake. Twenty-four percent and 13% of infants had insufficient and deficient 25OHD levels at 4 months. Unsupplemented breast-fed infants have the highest level of insufficiency (67%) compared with formula-fed infants (2%). Factors associated with infant serum 25OHD levels at 4 months included breast feeding, supplementation, and time outside. WSW have a high prevalence of insufficiency and deficiency during pregnancy which doubles 4 months after birth. Breast-fed infants of WSW are rarely considered at risk of vitamin D insufficiency but have high rates compared with formula-fed infants. This is the first study to show the finding that FST I WSW have significantly lower levels of 25OHD than those with FST II-IV (difference adjusted for diet and time outside 14 (95%CI 7-21) nmol/L).


Subject(s)
Diet , Nutritional Status , Vitamin D Deficiency/epidemiology , White People , Adult , Breast Feeding , Cohort Studies , Dietary Supplements , England/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Postpartum Period , Pregnancy , Seasons , Vitamin D/administration & dosage , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood
3.
Photochem Photobiol Sci ; 14(6): 1073-81, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25969962

ABSTRACT

A detailed map of the available UV across the UK from 2003 to 2012 is provided. A suite of data derived from climatologies and satellite observations are used to calculate spectral UV irradiance and related weighted doses (erythema, DNA damage, vitamin D). The result is a well-validated tool that has two advantages: (i) the output is simulated spectral UV irradiance that can be weighted with any action spectrum for use in any research studies that require ambient UV data, (ii) reliance on instruments with planned operational lives of at least several years that ensures data and method homogeneity for extension to future studies. The model-derived doses are satisfactory validated against spectral ground-based measurements at two sites. According to the calculated climatology, the southern part of the UK receives 1.5-2 times more UV than the north during spring, summer and autumn. During wintertime, the UV doses in the far north are an order of magnitude lower than southern values. Even for the same latitude, regional variations of cloudiness result in doses at coastal sites being up to 25% higher than inland areas.


Subject(s)
Health Status Indicators , Models, Theoretical , Ultraviolet Rays , Humans , Ireland , Radiation Dosage , United Kingdom
4.
Rheumatology (Oxford) ; 51(3): 544-51, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22120462

ABSTRACT

OBJECTIVE: To determine the relationship between serum vitamin D and markers of subclinical cardiovascular disease (CVD) in patients with SLE. METHODS: We recruited SLE patients (≥ 4 ACR 1997 criteria) from outpatient clinics between January 2007 and January 2009. Vitamin D deficiency was defined as serum 25(OH)D <20 ng/ml measured by ELISA. Disease activity was measured using the SLEDAI-2K score. Aortic pulse wave velocity (aPWV) was measured using PulseTrace 3600 (Micromedical) and carotid plaque (CP) and intima-media thickness (IMT) assessed using B-mode Doppler US. RESULTS: Seventy-five women with SLE were recruited with a median (interquartile range) disease duration of 16 (8-27) years. Patients with vitamin D deficiency had higher BMI (P = 0.014) and insulin resistance (P = 0.023) than those with 25(OH)D >20 ng/ml. Subjects with SLEDAI-2K ≥ 4 had lower 25(OH)D than those with SLEDAI-2K <4 (median 12.9 vs 20.3 ng/ml, P = 0.031). Aortic stiffness was significantly associated with serum 25(OH)D [log(aPWV) ß (95% CI) -0.0217 (-0.038, -0.005), P = 0.010] independently of BMI, CVD risk factors and serum insulin. Adjustment for disease activity reduced the strength of the association. There was no association between 25(OH)D and CP or IMT. CONCLUSIONS: Vitamin D deficiency is associated with increased aortic stiffness in SLE, independent of CVD risk factors and insulin. Increased inflammatory disease activity may be the mechanism by which vitamin D deficiency mediates vascular stiffness in this patient group.


Subject(s)
Cardiovascular Diseases/physiopathology , Lupus Erythematosus, Systemic/physiopathology , Vascular Stiffness/physiology , Vitamin D Deficiency/physiopathology , Adolescent , Adult , Aged , Biomarkers , Cardiovascular Diseases/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Middle Aged , Prevalence , Risk Factors , Severity of Illness Index , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Young Adult
6.
Vet Dermatol ; 23(2): 125-30, e27-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22141403

ABSTRACT

Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured in 20 dogs with atopic dermatitis prior to treatment with a standard therapeutic dosage of prednisolone (0.93-1.06 mg/kg) every other day for 5 weeks after 7 days of treatment with the same dosage once daily. The severity of their physical signs was scored before and 6 weeks after prednisolone treatment by the canine atopic dermatitis extent and severity index version 3 (CADESI-03) and the Edinburgh Pruritus Scale (EPS). The 20 dogs with atopic dermatitis that were treated with prednisolone did not have significantly lower serum concentrations of 25(OH)D than a group of 36 healthy dogs, and the physical severity of the atopic dermatitis was not correlated to pretreatment serum 25(OH)D concentrations. However, dogs which had a marked improvement of their physical signs, defined by a post-treatment EPS score of 0 and/or an 85% reduction in CADESI-03 score, had significantly higher pretreatment serum 25(OH)D concentrations than dogs with a suboptimal response (P = 0.003 and P = 0.03, respectively). Serum 25(OH)D concentrations were also measured in a previously published cohort of atopic dogs that were treated with ciclosporin. This cohort of dogs was recruited in a similar time frame to the prednisolone-treated dogs, and all samples were handled in the same way. In contrast to the prednisolone-treated dogs, there was no significant difference in 25(OH)D concentrations in dogs that responded optimally to ciclosporin compared with suboptimal responders. Additional studies are required to establish whether vitamin D has a synergistic therapeutic effect with prednisolone in dogs with atopic dermatitis.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Dermatitis, Atopic/veterinary , Dog Diseases/drug therapy , Prednisolone/therapeutic use , Vitamin D/analogs & derivatives , Animals , Cohort Studies , Dermatitis, Atopic/drug therapy , Dog Diseases/blood , Dogs , Vitamin D/blood
7.
Vet Dermatol ; 23(6): 481-e91, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23140314

ABSTRACT

BACKGROUND: Ciclosporin is widely used in the management of canine atopic dermatitis. In humans, ciclosporin therapy has been linked to disturbances in calcium metabolism and resultant skeletal disorders. OBJECTIVES: The objective of this study was to assess calcium homeostasis in dogs before and after a 6 week course of once daily oral ciclosporin at the licensed dose (5 mg/kg). ANIMALS: Sixteen client-owned dogs with spontaneous atopic dermatitis. METHODS: Serum concentrations of calcium, phosphate, creatinine, 25-hydroxyvitamin D, 1,25-dihyroxyvitamin D and plasma concentrations of ionized calcium and parathyroid hormone (PTH) were measured, together with the urinary fractional excretion of calcium and phosphate. The extent of skin lesions was scored using the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 and the degree of pruritus by the Edinburgh Pruritus Scale prior to and at the end of the study. RESULTS: The CADESI-03 and the Edinburgh Pruritus Scale scores decreased satisfactorily in all dogs by the end of the study. Plasma PTH concentrations were significantly increased (P = 0.02) following ciclosporin treatment, whereas all other biochemical parameters were not significantly different from their starting values. The increase in PTH was mild in most cases and the proportion of dogs that had a PTH concentration above the reference range was not significantly different following treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: This study indicates that ciclosporin has minimal impact on calcium metabolism in dogs with atopic dermatitis when used at the licensed and clinically effective dosage for 6 weeks.


Subject(s)
Calcium/metabolism , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Dermatitis, Atopic/veterinary , Dog Diseases/drug therapy , Animals , Calcium/blood , Dermatitis, Atopic/blood , Dermatitis, Atopic/drug therapy , Dog Diseases/blood , Dogs , Female , Homeostasis/drug effects , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Male , Parathyroid Hormone/blood , Vitamin D/analogs & derivatives , Vitamin D/blood
8.
Pediatrics ; 147(1)2021 01.
Article in English | MEDLINE | ID: mdl-33386335

ABSTRACT

BACKGROUND AND OBJECTIVES: Vitamin D is essential for healthy development of bones, but little is known about the effects of supplementation in young stunted children. Our objective was to assess the effect of vitamin D supplementation on risk of rickets and linear growth among Afghan children. METHODS: In this double-blind, placebo-controlled trial, 3046 children ages 1 to 11 months from inner-city Kabul were randomly assigned to receive oral vitamin D3 (100 000 IU) or placebo every 3 months for 18 months. Rickets Severity Score was calculated by using wrist and knee radiographs for 631 randomly selected infants at 18 months, and rickets was defined as a score >1.5. Weight and length were measured at baseline and 18 months by using standard techniques, and z scores were calculated. RESULTS: Mean (95% confidence interval [CI]) serum 25-hydroxyvitamin D (seasonally corrected) and dietary calcium intake were insufficient at 37 (35-39) nmol/L and 372 (327-418) mg/day, respectively. Prevalence of rickets was 5.5% (placebo) and 5.3% (vitamin D): odds ratio 0.96 (95% CI: 0.48 to 1.92); P = .9. The mean difference in height-for-age z score was 0.05 (95% CI: -0.05 to 0.15), P = .3, although the effect of vitamin D was greater for those consuming >300 mg/day of dietary calcium (0.14 [95% CI: 0 to 0.29]; P = .05). There were no between-group differences in weight-for-age or weight-for-height z scores. CONCLUSIONS: Except in those with higher calcium intake, vitamin D supplementation had no effect on rickets or growth.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Cholecalciferol/therapeutic use , Growth Disorders/drug therapy , Rickets/prevention & control , Afghanistan/epidemiology , Calcium, Dietary/administration & dosage , Double-Blind Method , Female , Humans , Infant , Infant, Newborn , Male , Parathyroid Hormone/blood , Prevalence , Rickets/epidemiology , Urban Population , Vitamin D/analogs & derivatives , Vitamin D/blood
9.
J Clin Endocrinol Metab ; 94(2): 559-63, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19033372

ABSTRACT

CONTEXT: There has been a resurgence of vitamin D deficiency among infants, toddlers, and adolescents in the United Kingdom. Myopathy is an important clinical symptom of vitamin D deficiency, yet it has not been widely studied. OBJECTIVE: Our objective was to investigate the relationship of baseline serum 25 hydroxyvitamin D [25(OH)D] concentration and PTH with muscle power and force. DESIGN: This was a cross-sectional study. SETTING: The study was community based in a secondary school. PARTICIPANTS: A total of 99 post-menarchal 12- to 14-yr-old females was included in the study. MAIN OUTCOME MEASURES: Jumping mechanography to measure muscle power, velocity, jump height, and Esslinger Fitness Index from a two-legged counter movement jump and force from multiple one-legged hops was performed. Body height, weight, and serum concentrations of 25(OH)D, PTH, and calcium were measured. RESULTS: Median serum 25(OH)D concentration was 21.3 nmol/liter (range 2.5-88.5) and PTH 3.7 pmol/liter (range 0.47-26.2). After correction for weight using a quadratic function, there was a positive relationship between 25(OH)D and jump velocity (P = 0.002), jump height (P = 0.005), power (P = 0.003), Esslinger Fitness Index (P = 0.003), and force (P = 0.05). There was a negative effect of PTH upon jump velocity (P = 0.04). CONCLUSION: From these data we conclude that vitamin D was significantly associated with muscle power and force in adolescent girls.


Subject(s)
Menarche , Muscle, Skeletal/physiology , Vitamin D/blood , Adolescent , Adolescent Nutritional Physiological Phenomena , Athletic Performance/physiology , Body Weight/physiology , Child , Cross-Sectional Studies , Female , Humans , Menarche/blood , Menarche/physiology , Muscle Strength/physiology , Parathyroid Hormone/blood , Vitamin D Deficiency/physiopathology
10.
Photodermatol Photoimmunol Photomed ; 24(2): 97-8, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18353091

ABSTRACT

Asian immigrants to the United Kingdom demonstrate much higher tuberculosis rates than the indigenous population. This is postulated to be because of their low vitamin D levels, consequent upon a combination of diet and their reduced ultraviolet (UV) exposure in the United Kingdom, because vitamin D enhances antimycobacterial activity in in vitro systems. The aim of this study was to examine the relationship between UVB exposure, vitamin D levels and tuberculo-immunity in Asian immigrants in the United Kingdom. Suberythemal UVB treatments were given to eight subjects on 3 consecutive days, using broadband UVB fluorescent lamps. Blood was sampled for 25-hydroxyvitamin D (25-OH D) and whole blood functional assays were performed for antimycobacterial immunity. The mean 25-OH D level increased from a baseline of 11.23 ng/ml (95% CI 6.7-20.39) to 20.39 ng/ml (95% CI 16.6-20) following UVB treatment, P<0.01. However, no significant change in antimycobacterial immunity occurred following UVB exposure. This pilot study in Asian subjects with good baseline tuberculo-immunity has not supported a role for UVB-induced 25-OH D in the immune response to Mycobacterium tuberculosis.


Subject(s)
Mycobacterium tuberculosis/immunology , Skin/radiation effects , Tuberculosis, Pulmonary/immunology , Ultraviolet Rays , Vitamin D/biosynthesis , Adult , Asia/ethnology , Dose-Response Relationship, Radiation , Emigration and Immigration , Female , Humans , Immunity, Innate , Male , Pilot Projects , Skin/metabolism , Tuberculosis, Pulmonary/microbiology , United Kingdom
11.
J Invest Dermatol ; 138(10): 2244-2252, 2018 10.
Article in English | MEDLINE | ID: mdl-29730334

ABSTRACT

Public health guidance recommends limiting sun exposure to sub-sunburn levels, but it is unknown whether these can gain vitamin D (for musculoskeletal health) while avoiding epidermal DNA damage (initiates skin cancer). Well-characterized healthy humans of all skin types (I-VI, lightest to darkest skin) were exposed to a low-dose series of solar simulated UVR of 20%-80% their individual sunburn threshold dose (minimal erythema dose). Significant UVR dose responses were seen for serum 25-hydroxyvitamin D and whole epidermal cyclobutane pyrimidine dimers (CPDs), with as little as 0.2 minimal erythema dose concurrently producing 25-hydroxyvitamin D and CPD. Fractional MEDs generated equivalent levels of whole epidermal CPD and 25-hydroxyvitamin D across all skin types. Crucially, we showed an epidermal gradient of CPD formation strongly correlated with skin darkness (r = 0.74, P < 0.0001), which reflected melanin content and showed increasing protection across the skin types, ranging from darkest skin, where high CPD levels occurred superficially, with none in the germinative basal layer, to lightest skin, where CPD levels were induced evenly across the epidermal depth. People with darker skin can be encouraged to use sub-sunburn UVR-exposure to enhance their vitamin D. In people with lighter skin, basal cell damage occurs concurrent with vitamin D synthesis at exquisitely low UVR levels, providing an explanation for their high skin cancer incidence; greater caution is required.


Subject(s)
Skin Neoplasms/genetics , Skin Pigmentation/drug effects , Skin/drug effects , Ultraviolet Rays , Vitamin D/analogs & derivatives , Vitamin D/pharmacology , Adult , DNA Damage , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Incidence , Male , Retrospective Studies , Skin/radiation effects , Skin Neoplasms/epidemiology , Skin Neoplasms/metabolism , Skin Pigmentation/radiation effects , United Kingdom/epidemiology , Vitamin D/metabolism , Vitamin D/radiation effects , Vitamins/pharmacology
12.
Bone ; 40(1): 200-4, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16950669

ABSTRACT

INTRODUCTION: Low vitamin D status is prevalent among South Asians living in the UK. The relationship, however, between serum 25-hydroxyvitamin D level (25OHD), serum parathyroid level (PTH) and bone mass in this group of women is unknown. The aim of this study was to determine the association between serum PTH, 25OHD and bone mass in a population based sample of young UK South Asian women. MATERIALS AND METHODS: Names of South Asian women aged 18 to 36 years of Pakistani origin living in the Greater Manchester area were identified from primary care registers using validated computer software. Subjects were invited to attend for (i) a blood test for assessment of serum calcium (Ca), albumin, PTH and 25OHD and (ii) for bone mineral density (BMD) scanning using the following: areal BMD at the hip (femoral neck, total hip) and lumbar spine using dual X-ray absorptiometry (Hologic QDR 4500), and volumetric BMD at the distal radius using peripheral quantitative computed tomography (Norland Stratec XCT 2000). Linear regression was used to determine the association between serum 25OHD, PTH and BMD at the different sites with adjustments made for age. RESULTS: In all, 78 women (mean age 29.2 years) were included in the analysis. Mean serum Ca level was 2.42 mmol/l, 25OHD, 7.9 ng/ml and PTH, 52.8 pg/ml. The majority of women (94%) had serum 25OHD levels 15 ng/ml, though rose progressively in subjects with levels below 10 ng/ml. Serum 25OHD was positively associated with BMD at the hip and spine while PTH was negatively associated with BMD at the hip and spine. When categorized by serum 25OHD level there was an increase in BMD at the total hip and distal radial site at least up to levels of 15 ng/ml. CONCLUSIONS: Despite widespread recognition, hypovitaminosis D is still prevalent among young UK South Asian women. In these women a decrease in serum 25OHD level

Subject(s)
Asian People , Bone Density , Parathyroid Hormone/blood , Vitamin D Deficiency/epidemiology , Vitamin D/analogs & derivatives , Adolescent , Adult , Female , Femur/diagnostic imaging , Humans , Lumbar Vertebrae/diagnostic imaging , Prevalence , Radiography , United Kingdom/epidemiology , United Kingdom/ethnology , Vitamin D/blood
13.
J Steroid Biochem Mol Biol ; 103(3-5): 477-9, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17197170

ABSTRACT

As a Supra-Regional Assay Service (SAS) laboratory, we receive samples from all over the UK. Of these some are sent frozen and others by post or courier. We have examined transport and storage conditions to see whether they affect the measurement of Vitamin D metabolites and potentially contribute to the variation in measurement of 25-hydroxyvitamin D (25OHD) seen in the DEQAS scheme. We have also examined the samples received during 2005. We found that different transport and storage conditions did not contribute significantly to the normal variation seen in measuring Vitamin D metabolites (CV% (+/-S.E.) for stored versus assay controls: 5.1+/-0.06% versus 4.5+/-0.04% for 25OHD and 10.8+/-1.0% versus 12.3+/-1.0% for 1,25D). A review of the service showed a 240% increase in samples received over the last 5 years. Despite an increased awareness of the need to measure Vitamin D status, in this cross-section of patient samples 92% of Asian and 86% of white patients were found to be Vitamin D-insufficient (<30 ng/ml) and 27% of Asian and 14% of white patients were profoundly deficient (<5 ng/ml) and at risk of bone disease.


Subject(s)
Vitamin D/analysis , Vitamin D/metabolism , Humans , United Kingdom
14.
J Steroid Biochem Mol Biol ; 103(3-5): 509-12, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17204416

ABSTRACT

The role of Vitamin D in the regulation of calcium absorption in the intestine is well recognized but the mechanisms of the effects on human genes are surprisingly poorly understood. We have determined the expression of transcripts of the apical membrane calcium transporter TRPV6, the cytoplasmic calcium binding protein calbindin-D9k, the basolateral plasma membrane Ca(2+)-ATPase (PMCA1) and the Vitamin D receptor (VDR) in normal endoscopic duodenal mucosal biopsies using quantitative real-time RT-PCR and related baseline expression to Vitamin D metabolites. TRPV6 transcript levels have been shown to be significantly correlated with serum 1,25(OH)(2)D levels in men, but not overall in women, where negative effects of age predominate. TRPV6 and VDR expression were significantly related in both men and women, but were significantly lower in older women. Associations with bone mineral density and fractional calcium absorption were also studied. In a second series of subjects, duodenal biopsies were incubated in organ culture for 6h with Vitamin D metabolites. TRPV6 expression was significantly increased by 1,25(OH)(2)D(3) (10(-9)mol/l) as was PMCA1 to a much smaller extent. TRPV6 expression also increased with 25(OH)D(3). CYP27B1 expression was found in all samples, and CYP24 transcripts were detected after incubation with 1,25(OH)(2)D(3) or 25(OH)D(3).


Subject(s)
Calcium Channels/genetics , Duodenum/drug effects , Duodenum/metabolism , Gene Expression Regulation/drug effects , Vitamin D/metabolism , Vitamin D/pharmacology , Adult , Aged , Aged, 80 and over , Bone Density/drug effects , Calcium/metabolism , Female , Humans , Male , Middle Aged
15.
Arch Intern Med ; 166(8): 902-8, 2006 Apr 24.
Article in English | MEDLINE | ID: mdl-16636217

ABSTRACT

BACKGROUND: Adipose-derived cytokines, including tumor necrosis factor alpha, may contribute to the inflammation that occurs in the metabolic syndrome. We investigated the effects of inhibition of tumor necrosis factor alpha with etanercept in patients with the metabolic syndrome. METHODS: Fifty-six subjects with the metabolic syndrome were randomized to administration of either etanercept or identical placebo, 50 mg subcutaneously once a week for 4 weeks. The C-reactive protein level was the primary end point. Effects on other inflammatory markers (including fibrinogen, interleukin 6, and adiponectin), insulin sensitivity, lipid levels, and body composition were also determined. RESULTS: Baseline characteristics were similar between the groups. Two subjects dropped out of each group, and etanercept was well tolerated throughout the study. The C-reactive protein levels decreased significantly in the treated compared with the placebo group (-2.4 +/- 0.4 vs 0.5 +/- 0.7 mg/L; P<.001). Adiponectin levels rose significantly in the etanercept group compared with the placebo group (0.8 +/- 0.4 vs -0.3 +/- 0.3 microg/mL; P = .03). Fibrinogen levels decreased (-68 +/- 16 vs -2 +/- 31 mg/dL [-2.0 +/- 0.47 vs -0.06 +/- 0.91 micromol/L]; P = .04) and interleukin 6 levels tended to decrease (-1.2 +/- 0.8 vs 0.5 +/- 0.5 ng/L; P = .07) in the etanercept-treated subjects compared with placebo, respectively. No changes occurred in body composition parameters or insulin sensitivity, but high-density lipoprotein levels tended to decrease in the etanercept group (-1 +/- 1 vs 2 +/- 1 mg/dL [-0.03 +/- 0.03 vs 0.05 +/- 0.03 mmol/L]; P = .06) compared with the placebo group. CONCLUSIONS: Etanercept reduces C-reactive protein levels and tends to improve other inflammatory cardiovascular risk indexes in patients with the metabolic syndrome. Etanercept may interrupt the inflammatory cascade that occurs with abdominal obesity. Further, longer-term studies are needed to determine the effects of tumor necrosis factor alpha inhibition on cardiovascular disease in patients with the metabolic syndrome.


Subject(s)
Immunoglobulin G/therapeutic use , Immunologic Factors/therapeutic use , Metabolic Syndrome/drug therapy , Receptors, Tumor Necrosis Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Adiponectin/blood , Adolescent , Adult , Biomarkers/blood , Body Composition , C-Reactive Protein/metabolism , Dose-Response Relationship, Drug , Etanercept , Female , Follow-Up Studies , Humans , Immunoglobulin G/administration & dosage , Immunologic Factors/administration & dosage , Injections, Subcutaneous , Male , Metabolic Syndrome/blood , Middle Aged , Receptors, Tumor Necrosis Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Retrospective Studies , Treatment Outcome
16.
J Feline Med Surg ; 19(4): 364-369, 2017 Apr.
Article in English | MEDLINE | ID: mdl-26795125

ABSTRACT

Objectives Vitamin D deficiency, as assessed by serum 25-hydroxyvitamin D (25[OH]D) concentrations, has been linked to markers of systemic inflammation in human and canine medicine. However, the relationship between vitamin D status and inflammation has not been previously investigated in cats. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and leukocyte counts in hospitalised sick cats. Methods Serum 25(OH)D concentrations and haematology profiles were measured in 170 consecutive hospitalised sick cats. A binary logistical regression model examined the relationship between serum 25(OH)D concentration, age, sex, breed and neutrophil, monocyte, eosinophil and lymphocyte counts. Results Cats with neutrophilia had lower serum 25(OH)D concentrations than cats with neutrophil concentrations below the upper limit of the reference interval (RI). There were no differences in serum 25(OH)D concentrations in cats with monocyte, lymphocyte or eosinophil counts above their respective RI compared with cats with counts below the upper limit of the RI. Conclusions and relevance Hospitalised cats with a neutrophil count above the RI had lower vitamin D status. There is a need to establish whether lower vitamin D status is a cause or consequence of increased neutrophil counts.


Subject(s)
Biomarkers/blood , Cat Diseases/diagnosis , Vitamin D Deficiency/veterinary , Vitamin D/analogs & derivatives , Animals , Case-Control Studies , Cat Diseases/blood , Cats , Female , Hospitalization , Leukocyte Count/veterinary , Male , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/diagnosis
17.
Am J Clin Nutr ; 106(2): 481-490, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28679555

ABSTRACT

Background: There are conflicting views in the literature as to whether vitamin D2 and vitamin D3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D.Objective: We aimed to investigate whether vitamin D2 or vitamin D3 fortified in juice or food, at a relatively low dose of 15 µg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial.Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20-64 y (n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 µg vitamin D2, biscuit supplemented with 15 µg vitamin D2, juice supplemented with 15 µg vitamin D3, or biscuit supplemented with 15 µg vitamin D3 daily for 12 wk. Serum 25(OH)D was measured by liquid chromatography-tandem mass spectrometry at baseline and at weeks 6 and 12 of the study.Results: Postintervention in the 2 ethnic groups combined, both the vitamin D3 biscuit and the vitamin D3 juice groups showed a significantly greater absolute incremental change (Δ) in total 25(OH)D when compared with the vitamin D2 biscuit group [Δ (95% CI): 15.3 nmol/L (7.4, 23.3 nmol/L) (P < 0.0003) and 16.0 nmol/L (8.0, 23.9 nmol/L) ( P < 0.0001)], the vitamin D2 juice group [Δ (95% CI): 16.3 nmol/L (8.4, 24.2 nmol/L) (P < 0.0001) and 16.9 nmol/L (9.0, 24.8 nmol/L) (P < 0.0001)], and the placebo group [Δ (95% CI): 42.3 nmol/L (34.4, 50.2 nmol/L) (P < 0.0001) and 42.9 nmol/L (35.0, 50.8 nmol/L) (P < 0.0002)].Conclusions: With the use of a daily dose of vitamin D relevant to public health recommendations (15 µg) and in vehicles relevant to food-fortification strategies, vitamin D3 was more effective than vitamin D2 in increasing serum 25(OH)D in the wintertime. Vitamin D3 may therefore be a preferential form to optimize vitamin D status within the general population. This trial was registered at www.controlled-trials.com as ISRCTN23421591.


Subject(s)
Cholecalciferol/pharmacology , Dietary Supplements , Ergocalciferols/pharmacology , Seasons , Vitamin D Deficiency/blood , Vitamin D/analogs & derivatives , Vitamins/pharmacology , Adult , Asia , Asian People , Cholecalciferol/blood , Cholecalciferol/therapeutic use , Double-Blind Method , Ergocalciferols/blood , Ergocalciferols/therapeutic use , Europe , Female , Food, Fortified , Humans , Male , Middle Aged , United Kingdom , Vitamin D/blood , Vitamin D Deficiency/ethnology , Vitamin D Deficiency/prevention & control , Vitamins/blood , Vitamins/therapeutic use , White People
18.
J Bone Miner Res ; 21(11): 1770-7, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17002582

ABSTRACT

UNLABELLED: Intestinal absorption of calcium affects bone mineralization and varies greatly. In human duodenum, expression of the calcium channel TRPV6 was directly related to blood 1,25-dihydroxyvitamin D in men, but effects of age with lower median vitamin D receptor levels were more significant in women. INTRODUCTION: The TRPV6 calcium channel/transporter is implicated in animal studies of intestinal calcium absorption, but in humans, its role and relationship to differences in mineral metabolism is unclear. We aimed to characterize TRPV6 expression in human intestine including defining relationships to the vitamin D endocrine system. MATERIALS AND METHODS: TRPV6 transcript expression was determined in endoscopic mucosal biopsies obtained from normal duodenum. Expression was compared with that in ileum and with in situ hybridization in archival tissues and related to sequence variants in genomic DNA. TRPV6 expression was related in 33 subjects to other transcripts involved in calcium absorption including the vitamin D receptor (VDR) and to blood vitamin D metabolites including 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. RESULTS: TRPV6 transcripts were readily detected in duodenum but not in ileum. Expression was highest in villous epithelial cells. Sequence variants in the coding and upstream regions of the gene did not affect TRPV6 expression. The relationship between duodenal TRPV6 expression and 1,25(OH)(2)D differed in men and women. In men, linear regression showed a strong association with 1,25(OH)(2)D (r = 0.87, p < 0.01), which was unaffected by age. In women, there was no significant overall relationship with 1,25(OH)(2)D, but there was a significant decrease with age (r = -0.69, p < 0.001). Individual expression of TRPV6 and VDR was significantly correlated. The group of older women (>50) had lower median levels of both TRPV6 and VDR transcripts than younger women (p < 0.001 and 0.02, respectively). CONCLUSIONS: Duodenal TRPV6 expression is vitamin D dependent in men, but not in older women, where expression of TRPV6 and VDR are both reduced. These findings can explain, at least in part, the lower fractional calcium absorption seen in older postmenopausal women.


Subject(s)
Aging , Duodenum/metabolism , Gene Expression Regulation , Receptors, Calcitriol/metabolism , TRPV Cation Channels/physiology , Vitamin D/metabolism , Adult , Aged , Aged, 80 and over , Base Sequence , Calcium/metabolism , Female , Humans , Ileum/metabolism , Male , Middle Aged , Molecular Sequence Data , Sex Factors , TRPV Cation Channels/metabolism
19.
J Steroid Biochem Mol Biol ; 164: 223-229, 2016 11.
Article in English | MEDLINE | ID: mdl-27016471

ABSTRACT

BACKGROUND: It is known that skin pigmentation reduces the penetration of ultraviolet radiation (UVR) and thus photosynthesis of 25-hydroxvitamin D (25(OH)D). However ethnic differences in 25(OH)D production remain to be elucidated. OBJECTIVE: The aim of this study was to investigate differences in vitamin D production between UK South Asian and Caucasian postmenopausal women, in response to a defined and controlled exposure to UVR. DESIGN: Seventeen women; 9 white Caucasian (skin phototype II and III), 8 South Asian women (skin phototype IV and V) participated in the study, acting as their own controls. Three blood samples were taken for the measurement of vitamin D status during the run in period (9days, no sunbed exposure) after which, all subjects underwent an identical UVR exposure protocol irrespective of skin colour (9 days, 3 sun bed sessions, 6, 8 and 8min respectively with approximately 80% body surface exposed). Skin tone was measured four times during the study. RESULTS: Despite consistently lower 25(OH)D levels in South Asian women, they were shown to synthesise vitamin D as efficiently as Caucasians when exposed to the same dose of UVR. Interestingly, the baseline level of vitamin D rather than ethnicity and skin tone influenced the amount of vitamin D synthesised. CONCLUSIONS: This study have found no ethnic differences in the synthesis of 25(OH)D, possibly due to the baseline differences in 25(OH)D concentration or due to the small population size used in this study. Applying mixed linear model, findings indicated no effect of ethnicity and skin tone on the production of vitamin D; baseline level and length of exposure were the critical factors. To confirm that ethnicity and skin tone has no effect on 25(OH)D production, a larger sample size study is required that considers other ethnic groups with highly pigmented skin. Initial vitamin D status influences the amount of UVB needed to reach equal serum concentrations.


Subject(s)
Vitamin D Deficiency/metabolism , Vitamin D/analogs & derivatives , Aged , Asian People , Female , Humans , Middle Aged , Parathyroid Hormone/blood , Parathyroid Hormone/metabolism , Postmenopause , Skin Pigmentation , Ultraviolet Rays , United Kingdom/epidemiology , Vitamin D/blood , Vitamin D/metabolism , Vitamin D Deficiency/blood , Vitamin D Deficiency/epidemiology , White People
20.
Vet Med Sci ; 2(2): 143, 2016 05.
Article in English | MEDLINE | ID: mdl-29067188

ABSTRACT

[This corrects the article DOI: 10.1002/vms3.11.].

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