PhD Student, Monash University
My research examines whether vitamin D supplementation can prevent diseases such as type 2 diabetes
I performed a rigorous randomised clinical trial as well as a comprehensive synthesis of the evidence (meta-analysis of data from previous randomised trials) to examine whether vitamin D supplementation, a simple and cost-effective intervention, could prevent cardiometabolic diseases such as type 2 diabetes by reducing related risk factors including glucose intolerance and inflammation. My research found that vitamin D supplementation had no effects on diabetes risk factors in overweight or obese individuals; however it improved chronic low-grade inflammation in patients with existing type 2 diabetes. My findings suggest that vitamin D supplementation may be a beneficial adjunct therapy to reduce sub-clinical inflammation in patients with type 2 diabetes, and potentially prevent or delay disease progression.
Abstract: The extraskeletal role of vitamin D is being increasingly recognised. This has important clinical implications, as vitamin D deficiency has reached epidemic proportions worldwide. Vitamin D has proposed anti-inflammatory properties, yet the role of vitamin D supplementation in reducing inflammation remains largely unknown. The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation, and to identify relevant knowledge gaps in the field.Medline, CINAHL, EMBASE and All EBM will be systematically searched for randomised controlled trials (RCTs) and systematic reviews of RCTs, comparing vitamin D supplementation with placebo, usual care or other pharmacological or non-pharmacological interventions. One reviewer will assess articles for eligibility according to prespecified selection criteria, after which 2 independent reviewers will perform data extraction and quality appraisal. Meta-analyses will be conducted where appropriate.Formal ethical approval is not required as no primary data is collected. This systematic review will identify potential clinical implications of vitamin D deficiency and supplementation, and will be disseminated through a peer-reviewed publication and at conference meetings, to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases.CRD42016037104.
Pub.: 07 Apr '16, Pinned: 27 Aug '17
Abstract: Despite Australia's sunny climate, low vitamin D levels are increasingly prevalent. Sun exposure is limited by long working hours, an increase in time spent indoors, and sun protection practices, and there is limited dietary vitamin D fortification. While the importance of vitamin D for bone mineralization is well known, its role as a protective agent against chronic diseases, such as type 2 diabetes and cardiovascular disease, is less understood. Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion, mainly via its anti-inflammatory properties, thereby decreasing the risk of development and progression of type 2 diabetes. The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D (25(OH)D), obtained through vitamin D supplementation, will increase insulin sensitivity and insulin secretion. A secondary aim is to determine whether these relationships are mediated by a reduction in underlying subclinical inflammation associated with obesity.Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old, with low vitamin D levels (25(OH)D < 50 nmol/l), will be randomly assigned to intervention or placebo. At baseline, participants will undergo a medical review and anthropometric measurements, including dual X-ray absorptiometry, an intravenous glucose tolerance test, muscle and fat biopsies, a hyperinsulinemic euglycemic clamp, and questionnaires assessing diet, physical activity, sun exposure, back and knee pain, and depression. The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D (cholecalciferol) daily, while the placebo group will receive apparently identical capsules, both for a period of 16 weeks. All measurements will be repeated at follow-up, with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group. Secondary outcome measures will compare changes in anthropometry, cardiovascular risk factors, and inflammatory markers.The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms, which are relevant for the prevention and management of type 2 diabetes.Clinicaltrials.gov ID: NCT02112721 .
Pub.: 08 Aug '15, Pinned: 27 Aug '17
Abstract: Vitamin D has been primarily known for its role in maintaining calcium and phosphorus homeostasis and promoting healthy bone mineralization. Emerging evidence suggests that vitamin D may have a plethora of other functions including cardiometabolic and immunological effects and a role in modulating human reproductive processes. Despite this, vitamin D deficiency (VDD) remains highly prevalent worldwide due to the limited availability of foods that are naturally high or fortified with vitamin D, increased sun avoidance behaviors and use of sunscreen due to fear of skin cancer, and increased sedentary indoor lifestyles, especially among those of reproductive age. This review examines current and emerging evidence for the role of vitamin D in reproductive health including in fertility, conception, and pregnancy outcomes, and outlines areas for future research. We found that existing evidence is based primarily on animal models and in vitro studies with some recent support from observational studies in humans. While these studies indicate that VDD may be a risk factor for adverse fertility and pregnancy outcomes, there is insufficient evidence to establish causality. Future efforts to clarify the benefits of vitamin D in reproductive health may bring about practical, simple, and cost-effective means of improving fertility and pregnancy outcomes.
Pub.: 27 May '16, Pinned: 27 Aug '17
Abstract: Maternal vitamin D deficiency has been implicated in adverse pregnancy outcomes. However, the association between vitamin D and inflammation, particularly adipokines, remains unexplored in pregnancy.In 102 overweight or obese pregnant women at high-risk of gestational diabetes (GDM), we investigated relationships between maternal 25-hydroxyvitamin D (25(OH)D) concentrations at 12-15 weeks gestation (baseline) and serum lipids, inflammatory markers, novel adipokines (omentin-1, visfatin, high molecular weight (HMW)-adiponectin), and subsequent pregnancy outcomes (GDM, preeclampsia, preterm birth PTB]). After adjustment for maternal factors (age, BMI, parity, ethnicity, and smoking status), baseline 25(OH)D concentrations were inversely associated with total cholesterol and triglycerides, and positively associated with HMW-adiponectin. Higher baseline 25(OH)D concentrations were associated with decreased fasting and 1-hour post-OGTT glucose and reduced risk of GDM at 26-28 weeks, as well as with longer gestation and reduced risk of PTB upon additional adjustment for caesarean section. Adding HMW-adiponectin to the multivariable models attenuated most associations, and HMW-adiponectin was a significant predictor in the models.Our findings suggest that lower maternal 25(OH)D concentrations in overweight/obese pregnant women at high-risk of GDM are associated with increased cardiometabolic risks during pregnancy and adverse pregnancy outcomes, and that these associations may be mediated by HMW-adiponectin. This article is protected by copyright. All rights reserved.
Pub.: 26 Jul '17, Pinned: 27 Aug '17
Abstract: Background: Vitamin D supplementation has been proposed as a potential strategy to prevent type 2 diabetes. Existing clinical trials have been limited by short duration, low doses of vitamin D, variability in participants' vitamin D-deficiency status, and the use of surrogate measures of body composition, insulin sensitivity, and insulin secretion.Objective: To address existing knowledge gaps, we conducted a double-blind, randomized, placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-standard methods. We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo.Design: Sixty-five overweight or obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] concentration ≤50 nmol/L) adults were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and after the intervention, participants received gold-standard assessments of body composition (via dual X-ray absorptiometry), insulin sensitivity (via hyperinsulinemic-euglycemic clamps), and insulin secretion [via an intravenous-glucose-tolerance tests (IVGTTs)].Results: Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m(2)): 30.9 ± 4.4]. 25(OH)D increased with vitamin D supplementation compared with placebo (57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L, respectively; P = 0.02). Vitamin D and placebo groups did not differ in change in insulin sensitivity (0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg(-1) · min(-1), respectively; P = 0.9) or first-phase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; P = 0.9). Results remained nonsignificant after adjustment for age, sex, percentage of body fat, sun exposure, physical activity, and dietary vitamin D intake (P > 0.1).Conclusions: Vitamin D supplementation does not improve insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults, despite using high-dose vitamin D supplementation and robust endpoint measures. Therefore, it is unlikely that vitamin D supplementation would be an effective strategy for reducing diabetes risk even in vitamin D-deficient populations. This trial was registered at clinicaltrials.gov as NCT02112721.
Pub.: 12 May '17, Pinned: 27 Aug '17