Effect of high-dose vitamin D supplementation in combination with weight loss diet on glucose homeostasis, insulin resistance, and matrix metalloproteinases in obese subjects with vitamin D deficiency: a double-blind, placebo-controlled, randomized clinical trial

2020 ◽  
Vol 45 (10) ◽  
pp. 1092-1098
Author(s):  
Soodabeh Aliashrafi ◽  
Mehrangiz Ebrahimi-Mameghani ◽  
Mohammad Asghari Jafarabadi ◽  
Lida Lotfi-Dizaji ◽  
Elnaz Vaghef-Mehrabany ◽  
...  

As there is limited and inconsistent evidence in potential role of vitamin D on insulin resistance and matrix metalloproteinases, this study aimed to examine the effect of vitamin D supplementation on glucose homeostasis, insulin resistance, and matrix metalloproteinases in obese subjects with vitamin D deficiency. A total of 44 participants with serum 25-hydroxyvitamin D (25(OH)D) level ≤ 50 nmol/L and body mass index (BMI) 30–40 kg/m2 were randomly allocated into receiving weight reduction diet with either 50 000 IU vitamin D3 pearl (n = 22) or placebo (n = 22) once weekly for 12 weeks. Primary outcomes were changes in fasting serum glucose (FSG), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and matrix metalloproteinases (MMPs). Secondary outcomes were changes in weight, BMI, 25(OH)D, calcium, phosphorous and parathyroid hormone (PTH). Sun exposure and dietary intakes were also assessed. Serum levels of 25(OH)D3 increased significantly with a simultaneous decrease in serum concentration of PTH in the vitamin D group. Weight, BMI, FSG, and MMP-9 decreased significantly in both groups, and there were significant differences in changes in weight, serum 25(OH)D3, PTH, and MMP-9 levels between the groups. Within- and between-groups analysis revealed no significant differences in serum calcium, phosphorous, serum insulin, HOMA-IR, QUICKI, and MMP-2 after intervention. Our results indicated that improvement in vitamin D status resulted in greater reductions in weight and MMP-9 during weight loss. These preliminary results are sufficient to warrant a bigger study group.

Author(s):  
Jennifer Miao ◽  
Katherine N. Bachmann ◽  
Shi Huang ◽  
Yan Ru Su ◽  
Jeffery Dusek ◽  
...  

Background Experimental and observational studies have suggested a link between vitamin D and cardiovascular and metabolic disease, but this has not been confirmed in randomized controlled trials. We sought to determine whether vitamin D supplementation reduces biomarkers of insulin resistance, inflammation, neurohormonal activation, and lipids. Methods and Results This was a prespecified, secondary analysis of the DAYLIGHT (Vitamin D Therapy in Individuals at High Risk of Hypertension) randomized controlled trial. We measured circulating homeostatic model assessment of insulin resistance, hs‐CRP (high‐sensitivity C‐reactive protein), N‐terminal pro‐B‐type natriuretic peptide, renin, aldosterone, and lipids at baseline and at 6 months in 289 individuals with low vitamin D status (25‐hydroxyvitamin‐D [25‐OH‐D] ≤25 ng/mL) receiving low‐dose (400 IU/d) versus high‐dose (4000 IU/d) vitamin D3 for 6 months. A meta‐analysis of randomized controlled trials reporting biomarker changes after vitamin D supplementation was then performed. Levels of 25‐OH‐D increased in the high‐dose relative to the low‐dose vitamin D group (+15.5 versus +4.6 ng/mL, P <0.001). Changes in biomarkers of glycemia, inflammation, and neurohormonal activation did not differ by dose. Lipids did not differ between groups, other than triglycerides, which increased in the high‐dose compared with the low‐dose group (+11.3 versus −6.2 mg/dL, P <0.001). The meta‐analysis showed potential modest decreases in homeostatic model assessment of insulin resistance and hs‐CRP, but no changes in low‐density lipoprotein, after vitamin D supplementation compared with control groups. Conclusions In the DAYLIGHT randomized controlled trial, high‐dose vitamin D supplementation did not improve biomarkers of glycemia, inflammation, neurohormonal activation, or lipids. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01240512.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Rolf Jorde ◽  
Moira Strand Hutchinson ◽  
Marie Kjærgaard ◽  
Monica Sneve ◽  
Guri Grimnes

Data were pooled from four randomized clinical trials with vitamin D performed in Tromsø with weight reduction, insulin sensitivity, bone density, and depression scores as endpoints. Serum lipids, glycated hemoglobin (HbA1c), and high sensitivity C-Reactive Protein, (HS-CRP) were measured at baseline and after 6–12 months of supplementation with vitamin D 20 000 IU–40 000 IU per week versus placebo. A total of 928 subjects who completed the interventions were included. At baseline the mean serum 25-hydroxyvitamin D (25(OH)D) level in those given vitamin D was 55.9 (20.9) nmol/L and the mean increase was 82.4 (40.1) nmol/L. Compared with the placebo group there was in the vitamin D group at the end of the studies a slight, but significant, increase in HbA1c of 0.04%, an increase in HS-CRP of 0.07 mg/L in those with serum 25(OH)D < 50 nmol/L, and in those with low baseline HDL-C and serum 25(OH)D < 50 nmol/L a slight decrease serum HDL-C of 0.08 mmol/L (P<0.05). No serious side-effects were seen. In conclusion, in subjects without vitamin D deficiency, there is no improvement in serum lipids, HbA1c, or HS-CRP with high dose vitamin D supplementation. If anything, the effect is negative.


2015 ◽  
Vol 18 (02) ◽  
pp. 1550008 ◽  
Author(s):  
Negin Masoudi Alavi ◽  
Mahla Madani ◽  
Mohsen Taghizadeh ◽  
Mohammad Reza Sharif

Purpose: To investigate the effect of weekly single high dose vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D], and non-specific musculoskeletal pain in female nurses. Methods: In this prospective study in Kashan/Iran, from April 1, 2014, through September 30, 2014, the 150 nurses with vitamin D deficiency received the weekly pearls of 50,000 units of vitamin D3 for 10 weeks. The serum level of 25(OH)D was measured before and after supplement therapy. The subjects were also asked to complete the Extended Nordic Musculoskeletal Questionnaire. All analyses were conducted with SPSS version 16. Results: After 10 weeks of intervention there was [Formula: see text][Formula: see text]ng/mL increase in 25(OH)D. The 82 nurses (54.7%) had 25(OH)D in normal range, while the 68 nurses (45.3%) were still vitamin D deficient. Weight could explain 15.4% increase in 25(OH)D. Before intervention 135 (90%), of nurses reported musculoskeletal pain in at least one region, after intervention this number decreased to 72.7%. There was a statistically significant improvement in musculoskeletal pain in neck, shoulders, upper back, lower back, hips/tights, knees, and ankles/feet after intervention. Conclusions: The weekly single high dose of vitamin D for 10 weeks could resolve vitamin D deficiency in about half of the patients. Patients with non-specific musculoskeletal pain might benefit from vitamin D supplementation.


2012 ◽  
Vol 167 (4) ◽  
pp. 569-578 ◽  
Author(s):  
Francisco J Ortega ◽  
Mónica Sabater ◽  
José M Moreno-Navarrete ◽  
Neus Pueyo ◽  
Patricia Botas ◽  
...  

ObjectiveIncreased circulating calprotectin has been reported in obese subjects but not in association with measures of insulin resistance and type 2 diabetes (T2D). The main aim of this study was to determine whether calprotectins in plasma and urine are associated with insulin resistance.DesignWe performed both cross-sectional and longitudinal (diet-induced weight loss) studies.MethodsCirculating calprotectin concentrations (ELISA), other inflammatory markers, homeostasis model assessment of insulin resistance (HOMA-IR), and parameters of glucose and lipid metabolism were evaluated in 298 subjects (185 with normal (NGT) and 62 with impaired (IGT) glucose tolerance and 51 T2D subjects). Calprotectin was also evaluated in urine samples from 71 participants (50 NGT and 21 subjects with IGT). Insulin sensitivity (SI, Minimal Model) was determined in a subset of 156 subjects, and the effects of weight loss were investigated in an independent cohort of obese subjects (n=19).ResultsCirculating calprotectin was significantly increased in IGT–T2D (independently of BMI) and positively associated with HOMA-IR, obesity measures, inflammatory markers, and parameters of glucose and lipid metabolism. Similar findings were reported for calprotectin concentrations in urine. In the subset of subjects, the association of calprotectin withSIwas independent of BMI and age. In fact,SItogether with C-reactive protein contributed to 27.4% of calprotectin variance after controlling for age and blood neutrophils count. Otherwise, weight loss led to decreased circulating calprotectin in parallel to fasting glucose and HOMA-IR.ConclusionThese findings suggest that circulating and urinary concentrations of calprotectin are linked to chronic low-grade inflammation and insulin resistance beyond obesity.


2019 ◽  
Vol 104 (9) ◽  
pp. 4033-4050 ◽  
Author(s):  
Thomas F Hiemstra ◽  
Kenneth Lim ◽  
Ravi Thadhani ◽  
JoAnn E Manson

Abstract Context A large body of experimental and observational data has implicated vitamin D deficiency in the development of cardiovascular disease. However, evidence to support routine vitamin D supplementation to prevent or treat cardiovascular disease is lacking. Design and Results A comprehensive literature review was performed using PubMed and other literature search engines. Mounting epidemiological evidence and data from Mendelian randomization studies support a link between vitamin D deficiency and adverse cardiovascular health outcomes, but randomized trial evidence to support vitamin D supplementation is sparse. Current public health guidelines restrict vitamin D intake recommendations to the maintenance of bone health and prevention of fractures. Two recently published large trials (VITAL and ViDA) that assessed the role of moderate- to high-dose vitamin D supplementation as primary prevention for cardiovascular outcomes in the general population had null results, and previous randomized trials have also been generally negative. These findings from general population cohorts that are largely replete in vitamin D may not be applicable to chronic kidney disease (CKD) populations, in which the use of active (1α-hydroxylated) vitamin D compounds is prevalent, or to other high-risk populations. Additionally, recent trials in the CKD population, as well as trials using vitamin D analogs, have been limited. Conclusions Current randomized trials of vitamin D supplementation do not support benefits for cardiovascular health, but the evidence remains inconclusive. Additional randomized trials assessing larger numbers of participants with low baseline vitamin D levels, having longer follow-up periods, and testing higher vitamin D dosages are needed to guide clinical practice.


2018 ◽  
Vol 103 (2) ◽  
pp. e1.9-e1
Author(s):  
Christiansen Nanna ◽  
Ashraf Saleha

AimsPatients with cystic fibrosis (CF) require supplementation of fat-soluble vitamins due to the effects of the disease on the pancreas and the resulting inability of absorb fat effectively.1The study aimed to assess the effectiveness of current of vitamin D supplementation to achieve adequate serum Vitamin D (25OHD) levels in paediatric CF patients.2 Secondly, this study assessed the effectiveness of ‘Stoss’ therapy (a high dose vitamin D therapy administered every three months) as an alternative to daily vitamin D supplementation for patients with known poor compliance.3MethodsVitamin D doses and serum 25OHD levels between January and December 2016 were reviewed for paediatric CF patients at a UK centre. Data was collected for 138 paediatric patients. The ‘clinical record summary’ system was used to extract the data which included age, hospital number, weight in 2015 and 2016, 25OHD levels from 2015 and 2016, vitamin D dose before each level and pancreatic status.Data was entered onto Statistical Package for the Social Sciences (SPSS) system for analysis. A paired T-test was conducted to ascertain if there was a significant difference in weekly/kg doses between patients that were sufficient (25OHD>50 nmol/L) and insufficient (25OHD<50 nmol/L).ResultsData was collected for a total of 138 patients. The data from only 70 patients was analysed when investigating the first objective, as all other patients did not have 25OHD levels available for both 2015 and 2016. A further five patients wereexcluded and analysed seperately due to receiving Stoss therapy. The weekly Vitamin D dose range was very wide for both years with 43% (n=40) of patients requiring additional vitamin D in addition to Aquadeks (CF multivitamin preparation). There was no significant difference in Vitamin D doses between patients with sufficient and insufficient 25OHD levels. This was thecase for both 2015 (p=0.432) and 2016 (p=0.192). The daily supplementation doses were successful at maintaining vitamin D sufficiency for 83% of patients in 2015 and 93% in 2016.Out of the 5 patients who received ‘Stoss’ therapy, 3 had an increase in 25OHD levels. However, only one of the patients had a significant increase leading to sufficient 25OHD levels. In 2 cases there was actually a 60%–68% decrease in 25OHD levels, which lead to these patients developing vitamin D deficiency.ConclusionThis study was useful in determining the effectiveness of current Vitamin D dosing. The results suggest that patients having insufficient 25OHD levels may not be due to an inadequacy of doses provided in the current guideline, as there was no significant difference in dose between patients with sufficient and insufficient 25OHD levels. Given the patient group, the difference could be attributable to a lack of compliance to daily therapies in the patients with insufficient 25OHD levels or even differences in individual responses to therapy.In this sample, ‘Stoss’ therapy is not effective in maintaining sufficient 25OHD levels. Although the data for this part of the study was very limited, it identifies a need to investigate the effectiveness of ‘Stoss’ therapy further.ReferencesFerguson JH, Chang AB. Vitamin D supplementation for cystic fibrosis. Cochrane Database of Syst Rev [Internet] 2014. http://onlinelibrary.wiley.com/ & doi:10.1002/14651858.CD007298.pub3/pdf [Available: 2017April 12].Green D, Carson K, Leonard A, et al. Current treatment recommendations for correcting vitamin D deficiency in paediatric patients with cystic fibrosis is inadequate. J Pediatr2008;4:554–559.Shepherd D, Belessis Y, Katz, et al. Single high-dose oral vitamin D3 (stoss) therapy: A solution to vitamin D deficiency in children with cystic fibrosis?J Cyst Fibros2013;2:177–182.


2018 ◽  
Vol 15 (4) ◽  
pp. 294-301 ◽  
Author(s):  
Leila Hadjadj ◽  
Szabolcs Várbíró ◽  
Eszter Mária Horváth ◽  
Anna Monori-Kiss ◽  
Éva Pál ◽  
...  

Hyperandrogenic state in females is accompanied with metabolic syndrome, insulin resistance and vascular pathologies. A total of 67%–85% of hyperandrogenic women suffer also from vitamin D deficiency. We aimed to check a potential interplay between hyperandrogenism and vitamin D deficiency in producing insulin resistance and effects on coronary resistance arteries. Adolescent female rats were divided into four groups, 11–12 animals in each. Transdermal testosterone-treated and vehicle-treated animals were kept either on vitamin D-deficient or on vitamin D-supplemented diet for 8 weeks. Plasma sexual steroid, insulin, leptin and vitamin D plasma levels were measured, and oral glucose tolerance test was performed. In coronary arterioles, insulin receptor and vitamin D receptor expressions were tested by immunohistochemistry, and insulin-induced relaxation was measured in vitro on isolated coronary resistance artery segments. Testosterone impaired glucose tolerance, and it diminished insulin relaxation but did not affect the expression of insulin and vitamin D receptors in vascular tissue. Vitamin D deficiency elevated postprandial insulin levels and homeostatic model assessment insulin resistance. It also diminished insulin-induced coronary arteriole relaxation, while it raised the expression of vitamin D and insulin receptors in the endothelial and medial layers. Our conclusion is that both hyperandrogenism and vitamin D deficiency reduce sensitivity of coronary vascular tissue to insulin, but they do it with different mechanisms.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Amanda Zaleski ◽  
Gregory Panza ◽  
Heather Swales ◽  
Pankaj Arora ◽  
Christopher Newton-Cheh ◽  
...  

Introduction. Vitamin D deficiency is associated with the onset and progression of hypertension and cardiovascular disease (CVD). However, mechanisms underlying vitamin D deficiency-mediated increased risk of CVD remain unknown. We sought to examine the differential effect of high-dose versus low-dose vitamin D supplementation on markers of arterial stiffness among ~40 vitamin D deficient adults with prehypertension.Methods. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D3 for 6 months. 24 hr ambulatory blood pressure (BP), carotid-femoral pulse wave velocity, and pulse wave analyses were obtained at baseline and after 6 months of vitamin D supplementation.Results. There were no changes in resting BP or pulse wave velocity over 6 mo regardless of vitamin D dose (allp>0.202). High-dose vitamin D decreased augmentation index and pressure by 12.3 ± 5.3% (p=0.047) and 4.0 ± 1.5 mmHg (p=0.02), respectively. However, these decreases in arterial stiffness were not associated with increases in serum 25-hydroxyvitamin D over 6 mo (p=0.425).Conclusion. High-dose vitamin D supplementation appears to lower surrogate measures of arterial stiffness but not indices of central pulse wave velocity.Clinical Trial Registration. This trial is registered with www.clinicaltrials.gov (Unique Identifier:NCT01240512).


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