Laura Tripkovic

Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis

Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.

Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial

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.

Vitamin D deficiency as a public health issue: using vitamin D 2 or vitamin D 3 in future fortification strategies

The role of vitamin D in supporting the growth and maintenance of the skeleton is robust; with recent research also suggesting a beneficial link between vitamin D and other non-skeletal health outcomes, including immune function, cardiovascular health and cancer. Despite this, vitamin D deficiency remains a global public health issue, with a renewed focus in the UK following the publication of Public Health Englands new Dietary Vitamin D Requirements. Natural sources of vitamin D (dietary and UVB exposure) are limited, and thus mechanisms are needed to allow individuals to achieve the new dietary recommendations. Mandatory or voluntary vitamin D food fortification may be one of the mechanisms to increase dietary vitamin D intakes and subsequently improve vitamin D status. However, for the food industry and public to make informed decisions, clarity is needed as to whether vitamins D2 and D3 are equally effective at raising total 25-hydroxyvitamin D (25(OH)D) concentrations as the evidence thus far is inconsistent. This review summarises the evidence to date behind the comparative efficacy of vitamins D2 and D3 at raising 25(OH)D concentrations, and the potential role of vitamin D food fortification as a public health policy to support attainment of dietary recommendations in the UK. The comparative efficacy of vitamins D2 and D3 has been investigated in several intervention trials, with most indicating that vitamin D3 is more effective at raising 25(OH)D concentrations. However, flaws in study designs (predominantly under powering) mean there remains a need for a large, robust randomised-controlled trial to provide conclusive evidence, which the future publication of the D2-D3 Study should provide (BBSRC DRINC funded: BB/I006192/1). This review also highlights outstanding questions and gaps in the research that need to be addressed to ensure the most efficacious and safe vitamin D food fortification practices are put in place. This further research, alongside cost, availability and ethical considerations (vitamin D3 is not suitable for vegans), will be instrumental in supporting government, decision-makers, industry and consumers in making informed choices about potential future vitamin D policy and practice.

Interindividual and intraindividual variation in pulse wave velocity measurements in a male population.

ObjectivePulse wave velocity (PWV) is a measure of arterial stiffness and a marker for cardiovascular disease. Although commonly used, there are only a few reports investigating the intersession and intrasession variability in PWV measurements, the determination of which is important in a mixed population when using PWV as a clinical marker. Therefore, the aim of this study was to investigate the variability in PWV measurements and factors that may influence PWV variability. MethodsA male population (n=8, age 30.9±9.0 years; BMI 25.1±4.0 kg/m2) underwent measurements of PWV and blood pressure several times in a single study visit and during six study visits over a 4–6-week period. During these study visits, experiments were performed at rest and following acute exercise and feeding. ResultsIntersession coefficients of variation (CVs) were 5.3 and 4.5% for radial–carotid (R–C) and carotid–femoral (C–F) PWVs, respectively, whereas intrasession CVs were 9.3 and 6.9% for R–C and C–F PWVs, respectively. Good reproducibility in PWV measurements was demonstrated by individual responses in the data; two of eight participants had significant differences in C–F PWV over time (P=0.05). There were significant increases in systolic blood pressure following acute exercise (P<0.0001) and feeding (P=0.05), but there were no consistent changes in PWV measurements. ConclusionThese data demonstrate the reproducibility of PWV and that PWV measurements are not acutely influenced by the metabolic state. This has implications for the use of PWV in human intervention trials where a mixed population is being investigated.

Associations between Baseline Vitamin D Status, Dietary Intake of Vitamin D and Calcium on Bone Health in Caucasian and South Asian Women: Further analysis of the D2-D3 Study

Vitamin D deficiency results in osteomalacia and leads to osteoporosis. Hypo-vitaminosis D is prevalent in the UK and our D-FINES study has shown vitamin D deficiency to be more common in South Asian (SA) women than Caucasian (CA) women living in South England. The aim of this study was to investigate the relationship between dietary vitamin D and calcium (Ca) intakes, vitamin D status and bone health indices among the women who took part in our D2-D3 study. The D2-D3 study was a vitamin D RCT previously reported in which vitamin D status was measured by LC/MS and 4d food diaries were used to measure dietary intake. The specific cross-sectional analysis was on the baseline data of 260 women and the longitudinal analysis on 59 women in the placebo group. Mean dietary vitamin D intakes in SA and CA women were 2·24 ± 2·0, 2·78 ± 2·3 μg, respectively. Mean dietary Ca intakes were 870 ± 261·5 mg in Caucasians and 703·5 ± 211·5 mg in South Asians. Vitamin D status of Caucasians (60·21 ± 25·6 nmol/l) was much higher than that of Asians (21·7 ± 18·1 nmol/l), (P < 0·001). Body weight and body fat in Asians and BMI in Caucasians were negatively correlated with serum 25-hydroxyvitamin D status (25OHD) (P < 0·05). In SA women, higher vitamin D intake was associated with higher vitamin D status (lowest vitamin D intake T1, 25(OH)D 16·35 nmol/l to highest vitamin D intake T3, 25(OH)D 35·08 nmol/l; F test for linearity, P = 0·017), remaining significant after adjusting for age and body size (P < 0·01). When Ca and vitamin D intakes were analysed together; increased combined intakes of Ca and vitamin D resulted in higher 25(OH)D (low Ca-low vitamin D, 25(OH)D 16·14 nmol/l to high Ca-high vitamin D, 25(OH)D 28·4 nmol/l; F test for linearity, P < 0·05), and this relationship remained significant after adjustments for body size (P < 0·05) in the SA women. As shown in the Figures below, increased Ca intakes resulted in higher BMC, in spite of the decreased vitamin D intakes (Medium Ca-High Vitamin D, BMC= 0·9070 g/cm to High Ca-Medium Vitamin D, BMC= 1·1613 g/cm; F test for linearity, P < 0·01) in POST-CA women. Women in the placebo group of the D2D3 study with vitamin D deficiency at baseline had a less pronounced decrease in vitamin D status during winter. These results demonstrate the importance of dietary Ca to bone health and the synergistic beneficial effects of combined dietary Ca and vitamin D intakes on vitamin D status and bone health. Further work is required on endogenous and exogenous factors affecting longitudinal changes in vitamin D status throughout the year.

The Comparative Effects of Vitamin D 2 Versus Vitamin D 3 Supplementation in Improving Serum 25(OH)D Status: A Review of the Evidence

At present, there appears to be a degree of controversy regarding the comparative effectiveness of vitamin D2 and D3 in raising and maintaining serum 25-hydroxyvitamin D (25(OH)D) levels. It was previously believed that the two vitamers were comparable in metabolic function; however, it is now known that when comparing vitamin D2 to D3, there are a small number of structural differences in the molecular makeup of these vitamers. Thus, the area of “vitamin D2 versus vitamin D3” research is expanding and exploring the possible mechanistic pathways that may highlight a clear and quantifiable difference between vitamin D2 and D3 that could have far-reaching consequences for both future vitamin D research and public health policy alike.