A pro-inflammatory diet in people with multiple sclerosis is associated with an increased rate of relapse and increased FLAIR lesion volume on MRI in early multiple sclerosis: A prospective cohort study.

BACKGROUND: A pro-inflammatory diet has been posited to induce chronic inflammation within the central nervous system (CNS), and multiple sclerosis (MS) is an inflammatory disease of the CNS. OBJECTIVE: We examined whether Dietary Inflammatory Index (DII®)) scores are associated with measures of MS progression and inflammatory activity. METHODS: A cohort with a first clinical diagnosis of CNS demyelination was followed annually (10 years, n = 223). At baseline, 5- and 10-year reviews, DII and energy-adjusted DII (E-DIITM) scores were calculated (food frequency questionnaire) and assessed as predictors of relapses, annualised change in disability (Expanded Disability Status Scale) and two magnetic resonance imaging measures; fluid-attenuated inversion recovery (FLAIR) lesion volume and black hole lesion volume. RESULTS: A more pro-inflammatory diet was associated with a higher relapse risk (highest vs. lowest E-DII quartile: hazard ratio = 2.24, 95% confidence interval (CI) = -1.16, 4.33, p = 0.02). When we limited analyses to those assessed on the same manufacturer of scanner and those with a first demyelinating event at study entry (to reduce error and disease heterogeneity), an association between E-DII score and FLAIR lesion volume was evident (ß = 0.38, 95% CI = 0.04, 0.72, p = 0.03). CONCLUSION: There is a longitudinal association between a higher DII and a worsening in relapse rate and periventricular FLAIR lesion volume in people with MS.

Evidence of low vitamin D intakes in the Australian population points to a need for data-driven nutrition policy for improving population vitamin D status.

BACKGROUND: Nearly one in four Australian adults is vitamin D deficient (serum 25-hydroxyvitamin D concentrations [25(OH)D] < 50 nmol L-1 ) and current vitamin D intakes in the Australian population are unknown. Internationally, vitamin D intakes are commonly below recommendations, although estimates generally rely on food composition data that do not include 25(OH)D. We aimed to estimate usual vitamin D intakes in the Australian population. METHODS: Nationally representative food consumption data were collected for Australians aged ≥ 2 years (n = 12,153) as part of the cross-sectional 2011-2013 Australian Health Survey (AHS). New analytical vitamin D food composition data for vitamin D3 , 25(OH)D3 , vitamin D2 and 25(OH)D2 were mapped to foods and beverages that were commonly consumed by AHS participants. Usual vitamin D intakes (µg day-1 ) by sex and age group were estimated using the National Cancer Institute method. RESULTS: Assuming a 25(OH)D bioactivity factor of 1, mean daily intakes of vitamin D ranged between 1.84 and 3.25 µg day-1 . Compared to the estimated average requirement of 10 µg day-1 recommended by the Institute of Medicine, more than 95% of people had inadequate vitamin D intakes. We estimated that no participant exceeded the Institute of Medicine's Upper Level of Intake (63-100 µg day-1 , depending on age group). CONCLUSIONS: Usual vitamin D intakes in Australia are low. This evidence, paired with the high prevalence of vitamin D deficiency in Australia, suggests that data-driven nutrition policy is required to safely increase dietary intakes of vitamin D and improve vitamin D status at the population level.

Vitamin D Food Fortification and Biofortification Increases Serum 25-Hydroxyvitamin D Concentrations in Adults and Children: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Low vitamin D status is a global public health issue that vitamin D food fortification and biofortification may help to alleviate. OBJECTIVES: We investigated the effect of vitamin D food fortification and biofortification on circulating 25-hydroxyvitamin D (25(OH)D) concentrations. We expanded the scope of earlier reviews to include adults and children, to evaluate effects by vitamin D vitamer, and investigate linear and nonlinear dose-response relations. METHODS: We conducted a systematic review and meta-analysis. We searched CINAHL, MEDLINE, PubMed, Embase, the Cochrane Library, and gray and unpublished literature sites for randomized controlled trials, including people of all ages, with the criteria: absence of illness affecting vitamin D absorption, duration ≥4 wk, equivalent placebo food control, dose quantification, dose ≥5 µg/d, baseline and endpoint or absolute change in 25(OH)D concentrations reported, random allocation, and participant blinding. Quality was assessed using the Jadad Scale. RESULTS: Data from 34 publications (2398 adults: 1345 intervention, 1053 controls; 1532 children: 970 intervention, 562 controls) were included. Random-effects meta-analysis of all studies combined (mean dose 16.2 µg/d) indicated a pooled treatment effect of 21.2 nmol/L (95% CI: 16.2, 26.2), with a greater effect for studies using cholecalciferol than ergocalciferol. Heterogeneity was high (I2  > 75%). Metaregression analyses for all studies combined suggested positive effect differences for baseline circulating 25(OH)D concentrations <50 nmol/L, dose ≥10 µg/d and a negative effect difference when the intervention arm included a calcium dose ≥500 mg/d greater than the control arm. Dose-response rates were found to be nonlinear (Wald test for nonlinearity P < 0.001). For all studies combined, a threshold occurred at ∼26 nmol/L for a dose of ∼21 µg/d. CONCLUSIONS: These results support use of vitamin D food fortification to improve circulating 25(OH)D circulations in populations. This work was registered with PROSPERO as CRD42020145497.

An exploratory study of diet in childhood and young adulthood and adult-onset multiple sclerosis.

There is little evidence on the role of diet in childhood/adolescence and multiple sclerosis (MS) in adulthood. The MS Sunshine Study recruited adults with recent-onset MS (n = 602) and matched controls (n = 653). Of these, 84% provided dietary recall for specific ages between childhood and young adulthood (6-10, 11-15 and 16-20 years). We used logistic regression to test associations between age-specific diet and case-control status. Consumption of fruit (all ages), yoghurt (all ages) and legumes (11-15 years) was associated with lower probability of adult-onset MS (all p < 0.05). These results suggest that healthy dietary habits between childhood and young adulthood may reduce MS risk.

High Prudent diet factor score predicts lower relapse hazard in early multiple sclerosis.

BACKGROUND: Dietary patterns and their association with subsequent clinical course have not been well studied in early multiple sclerosis (MS). OBJECTIVES: To describe dietary patterns in people in 5 years following first clinical demyelination and assess associations with MS conversion and relapse. METHODS: This study included baseline food frequency questionnaire dietary intake (entry to the Ausimmune Study) and 5-year follow-up; iterated principal factor analysis was applied. MS conversion and relapse risks were assessed by Cox proportional hazards models, adjusted for age, sex, study site, education, body mass index (BMI), smoking and omega-3 supplement use. RESULTS: In cases with a first clinical diagnosis of central nervous system (CNS) demyelination, we identified three major dietary patterns, 'Prudent', 'High-Vegetable' and 'Mixed', explaining 43%, 37% and 24% of diet variance in dietary intake, respectively. Fruits, vegetables, fish, wholegrains and nuts loaded highly on the Prudent pattern, starchy vegetables and legumes on the High-Vegetable pattern, and meats and alcohol on the Mixed pattern. Diet factor scores were not associated with MS conversion risk. Those with baseline Prudent scores above the median had significantly lower relapse risk (adjusted hazard ratio = 0.54, 95% confidence interval (CI) 0.37, 0.81) with some evidence of a plateau effect. CONCLUSION: Prudent diet factor score above the median was prospectively associated with lower relapse risk in the 5 years following the first clinical demyelinating event.

Prevalence and predictors of vitamin D deficiency in a nationally representative sample of Australian Aboriginal and Torres Strait Islander adults.

Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentration <50 nmol/l) is recognised as a public health problem globally. The present study details the prevalence and predictors of vitamin D deficiency in a nationally representative sample (n 3250) of Australian Aboriginal and Torres Strait Islander adults aged ≥18 years. We used data from the 2012-2013 Australian Aboriginal and Torres Strait Islander Health Survey (AATSIHS). Serum 25(OH)D concentrations were measured by liquid chromatography-tandem MS. Survey-weighted logistic regression models were used to determine the independent predictors of vitamin D deficiency. Approximately 27 % of adult AATSIHS participants were vitamin D deficient. Vitamin D deficiency was more prevalent in remote areas (39 %) than in non-remote areas (23 %). Independent predictors of vitamin D deficiency included assessment during winter (men, adjusted OR (aOR) 5·7; 95 % CI 2·2, 14·6; women, aOR 2·2; 95 % CI 1·3, 3·8) and spring (men, aOR 3·3; 95 % CI 1·4, 7·5; women, aOR 2·6; 95 % CI 1·5, 4·5) compared with summer, and obesity (men, aOR 2·6; 95 % CI 1·2, 5·4; women, aOR 4·3; 95 % CI 2·8, 6·8) compared with healthy weight. Statistically significant associations were evident for current smokers (men only, aOR 2·0; 95 % CI 1·2, 3·4), remote-dwelling women (aOR 2·0; 95 % CI 1·4, 2·9) and university-educated women (aOR 2·4; 95 % CI 1·2, 4·8). Given the high prevalence of vitamin D deficiency in this population, strategies to maintain adequate vitamin D status through safe sun exposure and dietary approaches are needed.

Hospitalisations for falls and hip fractures attributable to vitamin D deficiency in older Australians.

Vitamin D deficiency is associated with an increased risk of falls and fractures. Assuming this association is causal, we aimed to identify the number and proportion of hospitalisations for falls and hip fractures attributable to vitamin D deficiency (25 hydroxy D (25(OH)D) <50 nmol/l) in Australians aged ≥65 years. We used 25(OH)D data from the 2011/12 Australian Health Survey and relative risks from published meta-analyses to calculate population-attributable fractions for falls and hip fracture. We applied these to data published by the Australian Institute of Health and Welfare to calculate the number of events each year attributable to vitamin D deficiency. In men and women combined, 8·3 % of hospitalisations for falls (7991 events) and almost 8 % of hospitalisations for hip fractures (1315 events) were attributable to vitamin D deficiency. These findings suggest that, even in a sunny country such as Australia, vitamin D deficiency contributes to a considerable number of hospitalisations as a consequence of falls and for treatment of hip fracture in older Australians; in countries where the prevalence of vitamin D deficiency is higher, the impact will be even greater. It is important to mitigate vitamin D deficiency, but whether this should occur through supplementation or increased sun exposure needs consideration of the benefits, harms, practicalities and costs of both approaches.

Navigating dietary advice for multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease with no known cure. Numerous diets are promoted to reduce symptoms or even cure MS, despite insufficient evidence for any therapeutic diet. There are few qualitative studies exploring the experiences of people with MS in relation to diet, and no use of theory to explain the findings. PURPOSE: To explore the experiences of adults with MS when navigating dietary advice, their attitudes when making dietary decisions, and their needs regarding dietary resources and education. METHODS: In this qualitative study, we conducted six focus groups with people with MS (n = 33 plus one spouse without MS). Groups were audio-recorded and transcribed verbatim. Primary analysis used a general inductive approach with thematic analysis. Secondary analysis aligned themes with the constructs of the self-determination theory. RESULTS: Six themes emerged: (a) confusion about where to seek dietary advice; (b) scepticism towards national dietary guidelines; (c) personalized approaches to dietary change; (d) barriers to dietary changes; (e) judging if dietary changes work; and (f) wanting dietary guidelines for MS. CONCLUSION: People with MS are highly motivated to make dietary changes and improve their health. The self-determination theory explained why people with MS make dietary modifications, and the varying levels of motivation. MS-specific dietary resources and nutrition education need to incorporate ways to increase autonomous forms of motivation. Future dietary intervention studies could use the self-determination theory as a framework to improve long-term adherence to healthier diets.

Seafood, fatty acid biosynthesis genes, and multiple sclerosis susceptibility.

BACKGROUND: The role of omega-3 fatty acid in multiple sclerosis (MS) susceptibility is unclear. OBJECTIVE: To determine whether fish/seafood intake or genetic factors that regulate omega-3 fatty acids levels are associated with MS risk. METHODS: We examined the association of fish and shrimp consumption and 13 tag single nucleotide polymorphisms (SNPs) in FADS1, FADS2, and ELOV2 with risk of MS in 1153 individuals from the MS Sunshine Study, a case-control study of incident MS or clinically isolated syndrome (CIS), recruited from Kaiser Permanente Southern California. RESULTS: Consuming fish/seafood at least once a week or at least once a month with regular fish oil use was associated with 44% reduced odds of MS/CIS (adjusted OR = 0.56; 95% CI = 0.41-0.76; p = 0.0002) compared with consuming fish/seafood less than once a month and no fish oil supplementation. Two FADS2 SNPs (rs174611 and rs174618) were independently associated with a lower risk of MS (adjusted ORs = 0.74, 0.79, p = 0.0056, 0.0090, respectively). Association of FADS2 SNPs with MS risk was confirmed in an independent dataset. CONCLUSION: These findings suggest that omega-3 fatty acid intake may be an important modifiable risk factor for MS. This is consistent with the other known health benefits of fish consumption and complementary genetic studies supporting a key role for omega-3 regulation.

A Higher Mediterranean Diet Score, Including Unprocessed Red Meat, Is Associated with Reduced Risk of Central Nervous System Demyelination in a Case-Control Study of Australian Adults.

BACKGROUND: The evidence associating diet and risk of multiple sclerosis (MS) is inconclusive. OBJECTIVES: The aim of this study was to investigate associations between a Mediterranean diet and risk of a first clinical diagnosis of central nervous system demyelination (FCD), a common precursor to MS. METHODS: We used data from the 2003-2006 Ausimmune Study, an Australian multicenter, case-control study examining environmental risk factors for FCD, with participants matched on age, sex, and study region (282 cases, 558 controls; 18-59 y old; 78% female). The alternate Mediterranean diet score (aMED) was calculated based on data from a food-frequency questionnaire. We created a modified version of the aMED (aMED-Red) where ∼1 daily serving (65 g) of unprocessed red meat received 1 point. All other components remained the same as aMED. Conditional logistic regression (254 cases, 451 controls) was used to test associations between aMED and aMED-Red scores and categories and risk of FCD, adjusting for history of infectious mononucleosis, serum 25-hydroxyvitamin D concentrations, smoking, education, total energy intake, and dietary underreporting. RESULTS: There was no statistically significant association between aMED and risk of FCD [per 1-SD increase in aMED score: adjusted odds ratio (aOR): 0.89; 95% CI: 0.75, 1.06; P = 0.181]. There was evidence of a nonlinear relation between aMED-Red and risk of FCD when a quadratic term was used (P = 0.016). Compared with the lowest category of aMED-Red, higher categories were significantly associated with reduced risk of FCD, corresponding to a 37% (aOR: 0.63; 95% CI: 0.41, 0.98; P = 0.039), 52% (aOR: 0.48; 95% CI: 0.28, 0.83; P = 0.009), and 42% (aOR: 0.58; 95% CI: 0.35, 0.96; P = 0.034) reduced risk of FCD in categories 2, 3, and 4, respectively. CONCLUSIONS: A Mediterranean diet, including unprocessed red meat, was associated with reduced risk of FCD in this Australian adult population. The addition of unprocessed red meat to a Mediterranean diet may be beneficial for those at high risk of MS.

A healthy dietary pattern associates with a lower risk of a first clinical diagnosis of central nervous system demyelination.

BACKGROUND: The evidence associating diet and risk of multiple sclerosis is inconclusive. OBJECTIVE: We investigated associations between dietary patterns and risk of a first clinical diagnosis of central nervous system demyelination, a common precursor to multiple sclerosis. METHODS: We used data from the 2003-2006 Ausimmune Study, a case-control study examining environmental risk factors for a first clinical diagnosis of central nervous system demyelination, with participants matched on age, sex and study region. Using data from a food frequency questionnaire, dietary patterns were identified using principal component analysis. Conditional logistic regression models (n = 698, 252 cases, 446 controls) were adjusted for history of infectious mononucleosis, serum 25-hydroxyvitamin D concentrations, smoking, race, education, body mass index and dietary misreporting. RESULTS: We identified two major dietary patterns - healthy (high in poultry, fish, eggs, vegetables, legumes) and Western (high in meat, full-fat dairy; low in wholegrains, nuts, fresh fruit, low-fat dairy), explaining 9.3% and 7.5% of variability in diet, respectively. A one-standard deviation increase in the healthy pattern score was associated with a 25% reduced risk of a first clinical diagnosis of central nervous system demyelination (adjusted odds ratio 0.75; 95% confidence interval 0.60, 0.94; p = 0.011). There was no statistically significant association between the Western dietary pattern and risk of a first clinical diagnosis of central nervous system demyelination. CONCLUSION: Following healthy eating guidelines may be beneficial for those at high risk of multiple sclerosis.

Prevalence and predictors of vitamin D deficiency in a nationally representative sample of adults participating in the 2011-2013 Australian Health Survey.

Vitamin D deficiency is recognised as a public health problem globally, and a high prevalence of deficiency has previously been reported in Australia. This study details the prevalence of vitamin D deficiency in a nationally representative sample of Australian adults aged ≥25 years, using an internationally standardised method to measure serum 25-hydroxyvitamin D (25(OH)D) concentrations and identifies demographic and lifestyle factors associated with vitamin D deficiency. We used data from the 2011-2013 Australian Health Survey (n 5034 with complete information on potential predictors and serum 25(OH)D concentrations). Serum 25(OH)D concentrations were measured by a liquid chromatography-tandem MS that is certified to the reference measurement procedures developed by the National Institute of Standards and Technology, Ghent University and the US Centers for Disease Control and Prevention. Vitamin D deficiency and insufficiency were defined as serum 25(OH)D concentrations <50 nmol/l and 50 to <75 nmol/l, respectively. Overall, 20 % of participants (19 % men; 21 % women) were classified as vitamin D deficient, with a further 43 % classified as insufficient (45 % men; 42 % women). Independent predictors of vitamin D deficiency included being born in a country other than Australia or the main English-speaking countries, residing in southern (higher latitude) states of Australia, being assessed during winter or spring, being obese, smoking (women only), having low physical activity levels and not taking vitamin D or Ca supplements. Given our increasingly indoor lifestyles, there is a need to develop and promote strategies to maintain adequate vitamin D status through safe sun exposure and dietary approaches.

Dietary patterns, body mass index and inflammation: Pathways to depression and mental health problems in adolescents.

BACKGROUND: Observational studies suggest that dietary patterns may impact mental health outcomes, although biologically plausible pathways are yet to be tested. We aimed to elucidate the longitudinal relationship between dietary patterns, adiposity, inflammation and mental health including depressive symptoms in a population-based cohort of adolescents. METHODS: Data were provided from 843 adolescents participating in the Western Australian Pregnancy Cohort (Raine) Study at 14 and 17 years (y) of age. Structural equation modelling was applied to test our hypothesised models relating dietary patterns, energy intake and adiposity (body mass index) at 14 y to adiposity and the pro-inflammatory adipokine (leptin) and inflammation (high sensitivity C-reactive protein - hs-CRP) at 17 y, and these inflammatory markers to depressive symptoms (Beck Depression Inventory) and Internalising and Externalising Behavioral Problems (Child Behavior Check List Youth Self- Report) at 17 y. We further tested a reverse hypothesis model, with depression at 14 y as a predictor of dietary patterns at the same time-point. RESULTS: The tested models provided a good fit to the data. A 'Western' dietary pattern (high intake of red meat, takeaway, refined foods, and confectionary) at 14 y was associated with higher energy intake and BMI at 14 y, and with BMI and biomarkers of inflammation at 17 y (all p < .05). A 'Healthy' dietary pattern (high in fruit, vegetables, fish, whole-grains) was inversely associated with BMI and inflammation at 17 y (p < .05). Higher BMI at 14 y was associated with higher BMI (p < .01), leptin (p < .05), hs-CRP (p < .05), depressive symptoms (p < .05) and mental health problems (p < .05), all at 17 y. CONCLUSION: A 'Western' dietary pattern associates with an increased risk of mental health problems including depressive symptoms in adolescents, through biologically plausible pathways of adiposity and inflammation, whereas a 'Healthy' dietary pattern appears protective in these pathways. Longitudinal modelling into adulthood is indicated to confirm the complex associations of dietary patterns, adiposity, inflammation and mental health problems, including depressive symptoms.

Serum 25-hydroxyvitamin D concentrations and cardiometabolic risk factors in adolescents and young adults.

Evidence associating serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiometabolic risk factors is inconsistent and studies have largely been conducted in adult populations. We examined the prospective associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the West Australian Pregnancy Cohort (Raine) Study. Serum 25(OH)D concentrations, BMI, homoeostasis model assessment for insulin resistance (HOMA-IR), TAG, HDL-cholesterol and systolic blood pressure (SBP) were measured at the 17-year (n 1015) and 20-year (n 1117) follow-ups. Hierarchical linear mixed models with maximum likelihood estimation were used to investigate associations between serum 25(OH)D concentrations and cardiometabolic risk factors, accounting for potential confounders. In males and females, respectively, mean serum 25(OH)D concentrations were 73·6 (sd 28·2) and 75·4 (sd 25·9) nmol/l at 17 years and 70·0 (sd 24·2) and 74·3 (sd 26·2) nmol/l at 20 years. Deseasonalised serum 25(OH)D3 concentrations were inversely associated with BMI (coefficient -0·01; 95 % CI -0·03, -0·003; P=0·014). No change over time was detected in the association for males; for females, the inverse association was stronger at 20 years compared with 17 years. Serum 25(OH)D concentrations were inversely associated with log-HOMA-IR (coefficient -0·002; 95 % CI -0·003, -0·001; P<0·001) and positively associated with log-TAG in females (coefficient 0·002; 95 % CI 0·0008, 0·004; P=0·003). These associations did not vary over time. There were no significant associations between serum 25(OH)D concentrations and HDL-cholesterol or SBP. Clinical trials in those with insufficient vitamin D status may be warranted to determine any beneficial effect of vitamin D supplementation on insulin resistance, while monitoring for any deleterious effect on TAG.

Small Increments in Vitamin D Intake by Irish Adults over a Decade Show That Strategic Initiatives to Fortify the Food Supply Are Needed.

BACKGROUND: Food fortification could be an effective method of increasing vitamin D intakes and preventing deficiency with minimal risk of excessive dosing. OBJECTIVE: Secular trends in vitamin D intakes were examined over a 10-y period. METHODS: We compared vitamin D intakes among 18- to 64-y-old adults from the base diet, fortified foods, and supplements in 2 nationally representative dietary surveys in 1999 and 2009 implemented using the same methodology. RESULTS: There was a slight increase in the median (IQR) intake of vitamin D from 2.9 (3.2) to 3.5 (3.7) µg/d (mean ± SD, 4.3 ± 4.0 to 5.0 ± 6.4 µg). The median (IQR) intake from the base diet was 2.3 (1.6) µg/d in 1999 and 2.1 (1.8) µg/d in 2009. In vitamin D supplement users, median (IQR) intakes were 7.6 (6.7) and 8.7 (7.2) µg/d and the prevalence of inadequacy decreased from 67% to 57% in 2009. Although the consumption of vitamin D-containing supplements was similar in the 2 surveys (17% and 16%), the use of calcium-vitamin D supplements increased from 3% to 10% among women aged 50-64 y. The prevalence of fortified food consumption was also similar at 60%, and median (IQR) vitamin D intakes in consumers were 2.9 (2.2) and 3.7 (2.9) µg/d in 1999 and 2009, respectively. Mathematical modeling of food fortification using modified vitamin D composition data showed that there is potential to increase vitamin D intakes at the lower end of the distribution, without increasing the risk of exceeding the Tolerable Upper Intake Level. CONCLUSIONS: We report small increases in vitamin D intakes among Irish adults over a decade of focus on vitamin D and in the context of a voluntary fortification policy. Strategic management of vitamin D in the food supply is required to yield measurable benefits.

Low dietary intake of magnesium is associated with increased externalising behaviours in adolescents.

OBJECTIVE: Adequate Zn and Mg intakes may be beneficial for the prevention and treatment of mental health problems, such as depression, anxiety and attention-deficit hyperactivity disorder. We aimed to investigate the prospective association between dietary intakes of Zn and Mg and internalising and externalising behaviour problems in a population-based cohort of adolescents. DESIGN: Prospective analysis (general linear mixed models) of dietary intakes of Zn and Mg assessed using a validated FFQ and mental health symptoms assessed using the Youth Self-Report (YSR), adjusting for sex, physical activity, family income, supplement status, dietary misreporting, BMI, family functioning and energy intake. SETTING: Western Australian Pregnancy Cohort (Raine) Study. SUBJECTS: Adolescents (n 684) at the 14- and 17-year follow-ups. RESULTS: Higher dietary intake of Mg (per SD increase) was significantly associated with reduced externalising behaviours (ß = -1.45; 95% CI -2.40, -0.50; P = 0.003). There was a trend towards reduced externalising behaviours with higher Zn intake (per SD increase; ß = -0.73; 95% CI -1.57, 0.10; P = 0.085). CONCLUSIONS: The study shows an association between higher dietary Mg intake and reduced externalising behaviour problems in adolescents. We observed a similar trend, although not statistically significant, for Zn intake. Randomised controlled trials are necessary to determine any benefit of micronutrient supplementation in the prevention and treatment of mental health problems in adolescents.

Comparing the effects of sun exposure and vitamin D supplementation on vitamin D insufficiency, and immune and cardio-metabolic function: the Sun Exposure and Vitamin D Supplementation (SEDS) Study.

BACKGROUND: Adults living in the sunny Australian climate are at high risk of skin cancer, but vitamin D deficiency (defined here as a serum 25-hydroxyvitamin D (25(OH)D) concentration of less than 50 nmol/L) is also common. Vitamin D deficiency may be a risk factor for a range of diseases. However, the optimal strategies to achieve and maintain vitamin D adequacy (sun exposure, vitamin D supplementation or both), and whether sun exposure itself has benefits over and above initiating synthesis of vitamin D, remain unclear. The Sun Exposure and Vitamin D Supplementation (SEDS) Study aims to compare the effectiveness of sun exposure and vitamin D supplementation for the management of vitamin D insufficiency, and to test whether these management strategies differentially affect markers of immune and cardio-metabolic function. METHODS/DESIGN: The SEDS Study is a multi-centre, randomised controlled trial of two different daily doses of vitamin D supplementation, and placebo, in conjunction with guidance on two different patterns of sun exposure. Participants recruited from across Australia are aged 18-64 years and have a recent vitamin D test result showing a serum 25(OH)D level of 40-60 nmol/L. DISCUSSION: This paper discusses the rationale behind the study design, and considers the challenges but necessity of data collection within a non-institutionalised adult population, in order to address the study aims. We also discuss the challenges of participant recruitment and retention, ongoing engagement of referring medical practitioners and address issues of compliance and participant retention. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12613000290796 Registered 14 March 2013.

Vitamin D status and predictors of serum 25-hydroxyvitamin D concentrations in Western Australian adolescents.

Despite the importance of skeletal growth during adolescence, there is limited research reporting vitamin D status and its predictors in adolescents. Using prospective data from the Western Australian Pregnancy Cohort (Raine) Study, we investigated vitamin D status and predictors of serum 25-hydroxyvitamin D (25(OH)D) concentrations in adolescents. Serum 25(OH)D concentrations were measured in the same participants at 14 and 17 years (n 1045 at both time points). The percentage of adolescents with serum 25(OH)D concentrations < 50, 50-74·9 and ≥ 75 nmol/l was reported year-round and by month of blood collection. We examined the predictors of serum 25(OH)D concentrations, including sex, race, month of blood collection, physical activity, BMI, family income, and Ca and vitamin D intakes (n 919 at 14 years; n 570 at 17 years), using a general linear mixed model. At 14 years, 31 % of adolescents had serum 25(OH)D concentrations between 50 and 74·9 nmol/l and a further 4 % had concentrations < 50 nmol/l. At 17 years, 40 % of adolescents had serum 25(OH)D concentrations between 50 and 74·9 nmol/l and 12 % had concentrations < 50 nmol/l. Caucasian ethnicity, being sampled at the end of summer, exercising more, having a lower BMI, a higher Ca intake and a higher family income were significantly associated with higher serum 25(OH)D concentrations. The proportion of adolescents with serum 25(OH)D concentrations < 50 nmol/l was low in this Western Australian cohort. There is a need for international consensus on defining adequate vitamin D status in order to determine whether strategies to increase vitamin D status in adolescents are warranted.

Low serum 25-hydroxyvitamin D concentrations associate with non-alcoholic fatty liver disease in adolescents independent of adiposity.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) and serum 25-hydroxyvitamin D (s25[OH]D) concentrations are both associated with adiposity and insulin resistance (IR) and thus may be pathogenically linked. We aimed to determine the prevalence of vitamin D deficiency in adolescents with NAFLD and to investigate the prospective and cross-sectional associations between s25[OH]D concentrations and NAFLD. METHODS: Participants in the population-based West Australian Pregnancy (Raine) Cohort had seasonally adjusted s25(OH)D concentrations determined at ages 14 and then 17 years. NAFLD was diagnosed at 17 years using liver ultrasonography. Associations were examined after adjusting for potential confounders. Odds ratios (ORs) and confidence intervals (CIs) are reported per standard deviation in s25(OH)D concentrations. RESULTS: NAFLD was present in 16% (156/994) of adolescents. The majority of participants with NAFLD had either insufficient (51%) or deficient (17%) vitamin D status. s25(OH)D concentrations at 17 years were inversely associated with risk of NAFLD (OR 0.74, 95% CI 0.56, 0.97; P = 0.029), after adjusting for sex, race, physical activity, television/computer viewing, body mass index, and IR. The effect of s25(OH)D concentrations at 17 years was minimally affected after further adjusting for s25(OH)D concentrations at 14 years (OR 0.76, 95% CI 0.56, 1.03; P = 0.072). CONCLUSIONS: Lower s25(OH)D concentrations are significantly associated with NAFLD, independent of adiposity and IR. Screening for vitamin D deficiency in adolescents at risk of NAFLD is appropriate, and clinical trials investigating the effect of vitamin D supplementation in the prevention and treatment of NAFLD may be warranted.

Adequacy of vitamin D intakes in children and teenagers from the base diet, fortified foods and supplements.

OBJECTIVE: To describe vitamin D intakes in children and teenagers and the contribution from supplements and fortified foods in addition to the base diet. DESIGN: Analysis of 7 d weighed food records collected during the Children's and Teens' National Nutrition Surveys in Ireland. Food composition data for vitamin D were updated from international analytical sources. SETTING: Nationally representative cross-sectional dietary surveys. SUBJECTS: Children (n 594; 5-12 years) and teenagers (n 441; 13-17 years). RESULTS: Median vitamin D intakes were 1.9, 2.1 and 2.4 µg/d in 5-8-, 9-12- and 13-17-year-olds, respectively. The prevalence of vitamin D-containing supplement use was 21, 16 and 15% in 5-8-, 9-12- and 13-17-year-olds and median intakes in users ranged from 6.0 to 6.7 µg/d. The prevalence of inadequate intakes, defined as the percentage with mean daily intakes below the Estimated Average Requirement of 10 µg/d, ranged from 88 to 96% in supplement users. Foods fortified with vitamin D, mainly breakfast cereals, fat spreads and milk, were consumed by 71, 70 and 63 % of 5-8-, 9-12- and 13-17-year-olds. Non-supplement users who consumed vitamin D-fortified foods had median intakes of 1.9-2.5 µg/d, compared with 1.2-1.4 µg/d in those who did not consume fortified foods. CONCLUSIONS: It is currently not possible for children consuming the habitual diet to meet the US Institute of Medicine dietary reference intake for vitamin D. In the absence of nationally representative 25-hydroxyvitamin D data in children, the implications of this observation for prevalence of vitamin D deficiency and health consequences are speculative.