The AusD Study: A population-based study of the determinants of serum 25-hydroxyvitamin D concentration across a broad latitude range

Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18-75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study.

Cord blood 25-hydroxyvitamin D and fetal growth in the China-Anhui birth cohort study

We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: −110.5, −26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration.

Serum 25-hydroxyvitamin D and insulin resistance in people at high risk of cardiovascular disease: a euglycaemic hyperinsulinaemic clamp study

CONTEXT: In observational studies low serum 25-hydroxyvitamin D (25-OHD) concentration is associated with an increased risk of type 2 diabetes mellitus (DM). Increasing serum 25-OHD may have beneficial effects on insulin resistance or beta-cell function. Cross-sectional studies utilising sub-optimal methods for assessment of insulin sensitivity and serum 25-OHD concentration provide conflicting results.

OBJECTIVE: This study examined the relationship between serum 25-OHD concentration and insulin resistance in healthy overweight individuals at increased risk of cardiovascular disease, using optimal assessment techniques.

METHODS: 92 subjects (mean age 56.0, SD 6.0 years), who were healthy but overweight (mean BMI 30.9, SD 2.3 kg/m(2) ) underwent assessments of insulin sensitivity (two-step euglycaemic hyperinsulinaemic clamp, HOMA2-IR), beta-cell function (HOMA2%B), serum 25-OHD concentration and body composition (DEXA).

RESULTS: Mean total 25-OHD concentration was 32.2, range 21.8 - 46.6 nmol/L. No association was demonstrated between serum 25-OHD concentration and insulin resistance.

CONCLUSIONS: In this study using optimal assessment techniques to measure 25-OHD concentration, insulin sensitivity and body composition, there was no association between serum 25-OHD concentration and insulin resistance in healthy, overweight individuals at high risk of developing cardiovascular disease. This study suggests the documented inverse association between serum 25-OHD concentration and risk of type 2 DM is not mediated by a relationship between serum 25-OHD concentration and insulin resistance. 

APOA5 genotype influences the association between 25-hydroxyvitamin D and high density lipoprotein cholesterol

OBJECTIVE: Circulating levels of 25-hydroxyvitamin D (25OHD) are positively associated with high density lipoprotein (HDL) cholesterol. We sought to replicate a previously reported interaction between APOA5 genotype and vitamin D, and to examine whether HDL-associated genetic loci modify the association between serum 25OHD and HDL cholesterol. METHODS: We examined whether 42 single nucleotide polymorphisms (SNPs) modify the association between serum 25OHD and HDL cholesterol in the 1958 British Birth cohort (aged 45 years, n = 4978). RESULTS: We identified a borderline interaction between the SNP rs12272004 (near the APOA5) and serum 25OHD on HDL cholesterol (P(interaction) = 0.05). The interaction was particularly prominent among the samples collected during winter (P(interaction) = 0.001). None of the other loci showed an interaction with serum 25OHD concentrations on HDL cholesterol. CONCLUSIONS: Our study in 4978 British Whites provides further support that APOA5 genotype modifies the association between vitamin D metabolites and HDL cholesterol.

Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the third national health and nutrition examination survey

OBJECTIVE— To determine the association between serum 25-hydroxyvitamin D (25OHD) and diabetes risk and whether it varies by ethnicity.
RESEARCH DESIGN AND METHODS— We performed an analysis of data from participants who attended the morning examination of the Third National Health and Nutrition Examination Survey (1988–1994), a cross-sectional survey of a nationally representative sample of the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic blacks, and 1,726 Mexican Americans) aged ≥20 years with fasting and/or 2-h plasma glucose and serum insulin measurements.
RESULTS— Adjusting for sex, age, BMI, leisure activity, and quarter of year, ethnicityspecific odds ratios (ORs) for diabetes (fasting glucose ≥7.0 mmol/l) varied inversely across quartiles of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11– 0.60] for non-Hispanic whites and 0.17 [0.08–0.37] for Mexican Americans) in the highest vitamin D quartile (25OHD ≥81.0 nmol/l) compared with the lowest 25OHD (≥43.9 nmol/l). This inverse association
was not observed in non-Hispanic blacks. Homeostasis model assessment of insulin resistance (loge) was inversely associated with serum 25OHD in Mexican Americans (P ≥ 0.0024) and non-Hispanic whites (P≥0.058) but not non-Hispanic blacks (P≥0.93), adjusting for confounders.
CONCLUSIONS— These results show an inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans. The lack of an inverse association in non-Hispanic blacks may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.

Vitamin D-fortified milk achieves the targeted serum 25-hydroxyvitamin D concentration without affecting that of parathyroid hormone in New Zealand toddlers

For young children, the level of vitamin D required to ensure that most achieve targeted serum 25-hydroxyvitamin D [25(OH)D] ≥50 nmol/L has not been studied. We aimed to investigate the effect of vitamin D-fortified milk on serum 25(OH)D and parathyroid hormone (PTH) concentrations and to examine the dose–response relationship between vitamin D intake from study milks and serum 25(OH)D concentrations in healthy toddlers aged 12–20 mo living in Dunedin, New Zealand (latitude 46°S). Data from a 20-wk, partially blinded, randomized trial that investigated the effect of providing red meat or fortified toddler milk on the iron, zinc, iodine, and vitamin D status in young New Zealand children (n = 181; mean age 17 mo) were used. Adherence to the intervention was assessed by 7-d weighed diaries at wk 2, 7, 11, 15, and 19. Serum 25(OH)D concentration was measured at baseline and wk 20. Mean vitamin D intake provided by fortified milk was 3.7 μg/d (range, 0–10.4 μg/d). After 20 wk, serum 25(OH)D concentrations but not PTH were significantly different in the milk groups. The prevalence of having a serum 25(OH)D <50 nmol/L remained relatively unchanged at 43% in the meat group, whereas it significantly decreased to between 11 and 15% in those consuming fortified study milk. In New Zealand, vitamin D intake in young children is minimal. Our findings indicate that habitual consumption of vitamin D-fortified milk providing a mean intake of nearly 4 μg/d was effective in achieving adequate year-round serum 25(OH)D for most children.

Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years : results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle Study : AusDiab)

Context: Serum 25-hydroxyvitamin D [25(OH)D] concentration has been inversely associated with the prevalence of metabolic syndrome (MetS), but the relationship between 25(OH)D and incident MetS remains unclear.

Objective: We evaluated the prospective association between 25(OH)D, MetS, and its components in a large population-based cohort of adults aged 25 yr or older.

Design: We used baseline (1999–2000) and 5-yr follow-up data of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab).

Participants: Of the 11,247 adults evaluated at baseline, 6,537 returned for follow-up. We studied those without MetS at baseline and with complete data (n = 4164; mean age 50 yr; 58% women; 92% Europids).

Outcome Measures: We report the associations between baseline 25(OH)D and 5-yr MetS incidence and its components, adjusted for age, sex, ethnicity, season, latitude, smoking, family history of type 2 diabetes, physical activity, education, kidney function, waist circumference (WC), and baseline MetS components.

Results: A total of 528 incident cases (12.7%) of MetS developed over 5 yr. Compared with those in the highest quintile of 25(OH)D (≥34 ng/ml), MetS risk was significantly higher in people with 25(OH)D in the first (<18 ng/ml) and second (18–23 ng/ml) quintiles; odds ratio (95% confidence interval) = 1.41 (1.02–1.95) and 1.74 (1.28–2.37), respectively. Serum 25(OH)D was inversely associated with 5-yr WC (P < 0.001), triglycerides (P < 0.01), fasting glucose (P < 0.01), and homeostasis model assessment for insulin resistance (P < 0.001) but not with 2-h plasma glucose (P = 0.29), high-density lipoprotein cholesterol (P = 0.70), or blood pressure (P = 0.46).

Conclusions: In Australian adults, lower 25(OH)D concentrations were associated with increased MetS risk and higher WC, serum triglyceride, fasting glucose, and insulin resistance at 5 yr. Vitamin D supplementation studies are required to establish whether the link between vitamin D deficiency and MetS is causal.

Serum 25-hydroxyvitamin D deficiency and the 5-year incidence of CKD

Low serum 25-hydroxyvitamin D (25[OH]D) levels have been associated with chronic kidney disease in cross-sectional studies. However, this association has not been studied prospectively in a large general population–based cohort.

This prospective cohort study shows that vitamin D deficiency is associated with a higher annual incidence of albuminuria and reduced eGFR and independently predicts the 5-year incidence of albuminuria. These associations warrant further exploration in long-term prospective clinical trials.

Association between serum concentration of 25-hydroxyvitamin D and the risk of hip arthroplasty for osteoarthritis: result from a prospective cohort study

OBJECTIVES: There is ongoing debate regarding the optimal serum concentrations of 25-hydroxy-vitamin D for musculoskeletal health, including osteoarthritis (OA). The aim of this prospective cohort study was to determine whether serum 25-hydroxy-vitamin D concentrations were associated with the risk of hip arthroplasty for OA. DESIGN: This study examined 9135 participants from the Australian Diabetes, Obesity and Lifestyle Study who had serum 25-hydroxy-vitamin D measured in 1999-2000 and were aged ≥40 years at the commencement of arthroplasty data collection. The incidence of hip arthroplasty for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over an average 9.1 (standard deviation (SD) 2.7) years of follow-up, 201 hip arthroplasties for OA were identified (males n = 90; females n = 111). In males, a one-standard-deviation increase in 25-hydroxy-vitamin D was associated with a 25% increased incidence (HR 1.25, 95% CI 1.02-1.56), with a dose response relationship evident by quartiles of 25-hydroxy-vitamin D concentration (P for trend 0.04). These results were independent of age, body mass index (BMI), ethnicity, smoking status, physical activity, season of blood collection, latitude, hypertension and diabetes, area level disadvantage or after excluding those with extreme low 25-hydroxy-vitamin D concentrations. No significant association was observed in women (HR 1.10, 95% CI 0.87, 1.39). CONCLUSIONS: Increasing serum 25-hydroxy-vitamin D concentrations were associated with an increased risk of hip arthroplasty for OA in males, while no significant association was observed in females. The mechanism for the association warrants further investigation.

Interaction of dietary vitamin D-3 and sunlight exposure on B. indicus cattle: Animal performance, carcass traits, and meat quality

Attempts to improve beef tenderness through supplementation with dietary vitamin D-3 have been challenged by null results and negative impacts on animal performance and carcass traits. Because vitamin D-3 is also synthesised by the animal via ultraviolet radiation from sunlight, the effectiveness of supplementation with dietary vitamin D-3 may be modulated by the degree of exposure of the animal to sunlight. Hence, this work aimed to verify whether dietary vitamin D-3 modifies meat quality without negatively affecting animal performance and carcass traits in B. indicus beef cattle that were either exposed to or protected from natural sunlight. Forty-two (411 +/- 38 kg) Nellore-type castrated males were fed a high-concentrate diet for 45 days after assignment to a treatment group. The treatments comprised combinations of three levels of vitamin D3 [ViTD - none (V0) or 2 x 10(6) IU of vitamin D-3 administered for either 2 (V2) or 8 (V8) consecutive days pre-slaughter] and two shading conditions (SHADE - unshaded or shaded). The post-mortem (pm) measurements were taken in the Longissimus thoracis et lumborum muscle. The animal performance and carcass traits were unaffected by ViTD or SHADE The V2 treatment increased the Myofibrillar Fragmentation Index in shaded animals compared to unshaded ones. Animals under shade had higher muscle calcium concentration. There was no effect of either ViTD or SHADE on the shear force. The L* values were higher at 24 h pm than at 0 and 1 h pm, with no differences among the animals in the ViTD or SHADE groups. Higher a* values were observed among animals in the V8 group than in the V0 group, and higher b* values were observed among animals in the V8 group than in the V2 or V0 groups, which were not different. In conclusion, ViTD and SHADE did not affect animal performance, carcass traits or shear force, whereas animals receiving a lower ViTD dosage and SHADE exhibited altered myofibrillar fragmentation. ViTD affected the colour parameters, and changes in the lightness of the beef related to the time pm were found in meat from animals under SHADE. (c) 2012 Elsevier B.V. All rights reserved.

Serum concentrations of 25-hydroxyvitamin D and immunoglobulins in an older Swiss cohort: results of the Senior Labor Study.

BACKGROUND Vitamin D and the components of humoral immunity play important roles in human health. Older people have lower 25-hydroxyvitamin D (25(OH)D) serum levels than younger adults. We aimed to determine the levels of 25(OH)D serum concentrations in healthy senior citizens and to study their relationship to the levels of components of humoral immunity. METHODS A total of 1,470 healthy Swiss men and women, 60 years or older, were recruited for this study. A total of 179 subjects dropped out of the study because of elevated serum concentrations of C-reactive protein. Fasting blood sera were analyzed for 25(OH)D with the high-performance liquid chromatography (HPLC) and for parathyroid hormone (PTH), immunoglobulins and complement C4 and C3 concentrations with immunoassays. The percentage of participants in each of the four 25(OH)D deficiency groups--severely deficient (<10 ng/ml), deficient (10 to 20), insufficient (21 to 29 ng/ml) and normal (>=30 ng/ml)--were statistically compared. The relationship of the major components of the humoral system and age with 25(OH)D levels was also assessed. RESULTS About 66% of the subjects had insufficient levels of 25(OH)D. Normal levels of 25(OH)D were found in 26.1% of the subjects of which 21% were males and 30.5% were females (total study population). Severely deficient levels of 25(OH)D were found in 7.98% of the total study population. Low levels of 25(OH)D were positively associated with IgG2 (P = 0.01) and with C4 (P = 0.02), yet were inversely related to levels of IgG1 and IgA (P < 0.05) and C3 (P = 0.01). Serum levels of total IgA, IgG, IgG2 and IgG4 peaked together with 25(OH)D during late summer. CONCLUSIONS Approximately two-thirds of the healthy, older Swiss population presented with Vitamin D insufficiency. The incremental shift in IgA and C3 levels might not necessarily reflect a deranged humoral immune defense; however, given the high prevalence of vitamin D deficiency, the importance of this condition in humoral immunity will be worth looking at more closely. This study supports the role of vitamin D in the competent immune system.

The efficacy of a vitamin D-3 metabolite for improving the myofibrillar tenderness of meat from Bos indicus cattle

The influence of a once only administration of a metabolite of vitamin D-3 (HY center dot D-(R)-25-hydroxy vitamin D-3) on myofibrillar meat tenderness in Australian Brahman cattle was studied. Ninety-six Brahman steers of three phenotypes (indo-Brazil, US and US/European) and with two previous hormonal growth promotant (HGP) histories (implanted or not implanted with Compudose((R))) were fed a standard feedlot ration for 70 d. Treatment groups of 24 steers were offered daily 10 g/head HY center dot D-(R) (125 mg 25-hydroxyvitamin D-3) for 6, 4, or 2 d before slaughter. One other group of 24 steers was given the basal diet without HY center dot D-(R). Feed lot performance, blood and muscle samples and carcass quality data were collected at slaughter. Calcium, magnesium, potassium, sodium, iron and Vitamin D-3 metabolites were measured in plasma and longissimus dorsi muscle. Warner-Bratzler (WB) shear force (peak force, initial yield) and other objective meat quality measurements were made on the longissimus dorsi muscle of each steer after ageing for 1, 7 and 14 d post-mortem at 0-2 degrees C. There were no significant effects of HY center dot D-(R) supplements on average daily gain (ADG, 1.28-1.45 kg/d) over the experimental period. HY center dot D-(R) supplements given 6 d prior to slaughter resulted in significantly higher (P < 0.05) initial yield values compared to supplements given 2 d prior to slaughter. Supplementation had no significant effect on meat colour, ultimate pH, sarcomere length, cooking loss, instron compression or peak force. There was a significant treatment (HY center dot D-(R)) by phenotype/HGP interaction for peak force (P = 0.028), in which Indo-Brazil steers without previous HGP treatment responded positively (increased tenderness) to HY center dot D-(R) supplements at 2 d when compared with Indo-Brazil steers previously given HGP. There were no significant effects of treatment on other phenotypes. HY center dot D-(R) supplements did not affect muscle or plasma concentrations of calcium, potassium or sodium, but did significantly decrease plasma magnesium and iron concentrations when given 2 d before slaughter. There were no detectable amounts of 25-hydroxyvitamin D-3 in the blood or muscle of any cattle at slaughter. (c) 2005 Elsevier Ltd. All rights reserved.

Predictors of vitamin D-containing supplement use in the Australian population and associations between dose and serum 25-hydroxyvitamin D concentrations

Despite concerns about vitamin D deficiency in the Australian population, little is known about the prevalence and predictors of vitamin D-containing supplement use. We described the use of vitamin D-containing supplements, and investigated associations between supplemental vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, using a single 24-h dietary recall from the 2011-2013 Australian Health Survey (n = 12,153; ages ≥ 2 years). Multiple regression models were used to investigate predictors of vitamin D-containing supplement use in adults, and associations between dose and serum 25(OH)D concentrations/vitamin D sufficiency (≥50 nmol/L), adjusting for potential confounders. The prevalence of vitamin D-containing supplement use was 10%, 6% and 19% in children, adolescents and adults, respectively. Predictors of vitamin D-containing supplement use in adults included being female, advancing age, higher educational attainment, higher socio-economic status, not smoking, and greater physical activity. After adjusting for potential confounders, a 40 IU (1 µg) increase in vitamin D intake from supplements was associated with an increase of 0.41 nmol/L in serum 25(OH)D concentrations (95% CI 0.35, 0.47; p < 0.001). However, the prevalence of vitamin D-containing supplement use was generally low in the Australian population, particularly for single vitamin D supplements, with most supplement users obtaining only low levels of vitamin D from other supplement types.

Serum 25-hydroxyvitamin D concentration in relation to melanoma progress

Dr Wyatt’s study investigated the complex relationship between vitamin D and melanoma, specifically if vitamin D status is associated with more aggressive melanomas. Exposure to solar ultraviolet radiation is the principal risk factor for melanoma and also the main source of vitamin D. This research found that insufficient vitamin D at time of melanoma diagnosis is significantly associated with poorer prognosis (as defined by tumour thickness). These results will contribute to a more refined public health message concerning melanoma and vitamin D, particularly in Queensland, which has the highest global incidence of melanoma, but vitamin D deficiency is not uncommon.

Maternal 25-hydroxyvitamin D concentration and offspring birth size : effect modification by infant VDR genotype

Background/Objectives: We tested the hypothesis that the relationship between maternal 25-hydroxyvitamin D (25-(OH)D) and offspring birth size differs according to offspring vitamin D receptor (VDR) genotype (Apa1, Bsm1, Fok1 or Taq1).

Subjects/Methods: Mothers of 354 singleton babies had serum 25-(OH)D concentration measured at 28–30 weeks of gestation and consented to measurement of their babies soon after birth. DNA was extracted from the babies’ Guthrie cards.

Results: There was evidence of effect modification by infant FokI genotype. Babies of deficient mothers had lower birth weight with FF or Ff, but not ff genotype (P-value for interaction after adjustment for potential confounding factors=0.02), but thicker subscapular and suprailiac skinfolds with ff, but not FF or Ff genotype (P=0.008 and 0.02, respectively). Sample size was insufficient to investigate effect modification by the other VDR polymorphisms.

Conclusions: These preliminary findings suggest that studies of maternal vitamin D status and birth size may need to take VDR genotype into account.