Jara Valtueña

Vitamin D deficiency in Europe: pandemic?

Background: Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing 25(OH)D values from national health/nutrition surveys. Objective: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D deficiency in Europe. Design: The VDSP protocols were applied in 14 population studies [reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it] by using certified liquid chromatography–tandem mass spectrometry on biobanked sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n = 55,844). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data. Results: An overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55,844 European individuals had serum 25(OH)D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (October–March) and summer (April–November) periods, respectively. According to an alternate suggested definition of vitamin D deficiency (<50 nmol/L), the prevalence was 40.4%. Dark-skinned ethnic subgroups had much higher (3- to 71-fold) prevalence of serum 25(OH)D <30 nmol/L than did white populations. Conclusions: Vitamin D deficiency is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency in the majority of the European population.

Excessive sedentary time and low cardiorespiratory fitness in European adolescents: the HELENA study

Background The aims of this study were to examine what amount of sedentary time is associated with low cardiorespiratory fitness (CRF) in adolescents and whether this association is independent of physical activity. Methods The study comprised 1808 adolescents aged 12.5–17.5 years from 10 European cities. Sedentary time and moderate-to-vigorous physical activity (MVPA) were measured by accelerometer. CRF was assessed by the 20 m shuttle-run test. Adolescents were divided into two groups (high/low) according to FITNESSGRAM guidelines. Receiver-operating characteristic (ROC) analysis was used to determine thresholds that best discriminate between high and low CRF in adolescents. Results Adolescent girls had more sedentary time than boys (p<0.001). ROC analysis showed that girls spending ≥69% of waking time in sedentary activities had low CRF, but no significant threshold discriminated between high and low CRF in boys. Adolescent girls who exceeded this threshold had lower levels of CRF (p≤0.001) and were more likely to have a low CRF (OR 1.68, 95% CI 1.22 to 2.31) independent of centre, age and body mass index. The negative influence of excessive sedentary time on CRF remained significant (p=0.045) in adolescent girls who did not meet the physical activity guidelines (<60 min/day in MVPA) but was abolished (p>0.05) in those who met the recommendation (≥60 min/day in MVPA). Conclusion Excessive sedentary time is associated with low CRF in adolescent girls but not in boys. However, this adverse effect might be attenuated if adolescent girls meet the current physical activity guidelines.

Socio-economic factors and active commuting to school in urban Spanish adolescents: the AVENA study

BACKGROUND This study aimed: (i) to describe the patterns of commuting to school in urban Spanish adolescents; and (ii) to examine the associations between active commuting to school (ACS) and socio-economic factors. METHODS From the AVENA Study, 2183 adolescents (1142 females) aged 13-18.5 years were gathered. Mode and time of transportation to school were self-reported by the adolescents. Parental education level (primary, secondary or university degree), parental professional level (managerial, skilled worker or unskilled worker/unemployed) and the type of school (public or private) were self-reported by the parents. The relationships between ACS and socio-economic factors were analysed by binary logistic regression. RESULTS Nearly <65% of the adolescents reported ACS and 83% of them spent <15 min travelling to school. In male adolescents, maternal primary education level showed an odds ratio (OR) of 1.55 (95% confidence interval, 1.12-2.15), with respect to mothers with a university degree. In female adolescents, mothers with a primary education level showed an OR of 0.68 (0.50-0.92), with respect to mothers with a university degree. Low maternal professional level showed an OR of 1.70 (1.29-2.24), with respect to high maternal professional levels. Students attending public schools showed an OR of 3.47 (2.46-4.90), with respect to students from private schools. CONCLUSION Most of the adolescents actively commuted to school, yet the time spent commuting was low. Socio-economic level seems to be inversely related to the ACS in adolescents. Type of school and maternal educational level were the main predictors of ACS.

Health Effects Related to Low Vitamin D Concentrations: Beyond Bone Metabolism

Background: Vitamin D is essential for a vast number of physiologic processes, and thus adequate levels are necessary or advantageous for optimal health. During childhood and adolescence, an adequate vitamin D status is needed due to its important role in cell growth, skeletal structure, and development. Aims: To review the extraskeletal effects of vitamin D, focusing especially on children. Methods: Narrative review. Results: Low vitamin D concentrations seem to be significantly associated with all-cause mortality. Regular sunlight exposure and vitamin D supplementation in early childhood may offer protection against the development of type 1 diabetes. Epidemiological evidence supports the importance of adequate vitamin D levels for the prevention of a number of cancers, mainly breast and colorectal ones. There seems to be an inverse relation between 25(OH)D serum concentrations and cardiovascular diseases, some components of the metabolic syndrome, and physical fitness. Conclusions: Lifestyle and appropriate nutrition may prevent the long-term effect of hypovitaminosis D beyond mineral and bone metabolism.

Seasonal variation in physical activity and sedentary time in different European regions. The HELENA study

Abstract This report aims (1) to examine the association between seasonality and physical activity (PA) and sedentary time in European adolescents and (2) to investigate whether this association was influenced by geographical location (Central-North versus South of Europe), which implies more or less extreme weather and daylight hours. Valid data on PA, sedentary time and seasonality were obtained in 2173 adolescents (1175 females; 12.5–17.5 years) included in this study. Physical activity and sedentary time were measured by accelerometers. ANCOVA was conducted to analyse the differences in PA and sedentary time across seasons. Results showed that girls had lower levels of moderate to vigorous PA (MVPA) and average PA, and spent more time in sedentary activities in winter compared with spring (all P < 0.05). Stratified analyses showed differences in PA and sedentary time between winter and spring in European girls from Central-North of Europe (P < 0.05 for sedentary time). There were no differences between PA and sedentary time across seasonality in boys. In conclusion, winter is related with less time spent in MVPA, lower average PA and higher time spent in sedentary activities in European adolescent girls, compared with spring. These differences seem to mainly occur in Central-North Europe.

Bone Mass and Bone Metabolism Markers during Adolescence: The HELENA Study

Background/Aims: The assessment of bone mineral content (BMC) and density (BMD) status in children and adolescents is important for health and the prevention of diseases. Bone metabolic activity could provide early information on bone mass development. Our aim was to describe bone mass and metabolism markers according to age and Tanner stage in adolescents. Methods: Spanish adolescents (n = 345; 168 males and 177 females) aged 12.5–17.5 years participated in this cross-sectional study. Body composition variables were measured by dual-energy X-ray absorptiometry. Serum osteocalcin (n = 101), aminoterminal propeptide of type I procollagen (n = 92) and β-isomerized C-telopeptides (β-CTX, n = 65) and urine samples (β-CTX; n = 237) were analyzed by electrochemiluminescence immunoassay. Results: Analysis of covariance showed that females had higher values for BMC and BMD in most of the regions. Both males and females had a significant decrease in bone markers while sexual maturation increases (all p < 0.05). Males had an increased bone turnover compared to females (all p < 0.05, except for urine β-CTX in Tanner ≤IV). Conclusion: Our results support the evidence of dimorphic site-specific bone accretion between sexes and show an increased bone turnover in males, suggesting higher metabolic activity.

Associations of Dietary Calcium, Vitamin D, Milk Intakes, and 25-Hydroxyvitamin D With Bone Mass in Spanish Adolescents: The HELENA Study

Adequate nutrition is needed for the accrual of bone mass during the pre- and postpubertal growth periods. This study aimed to examine the associations between dietary calcium, vitamin D (calciferol), and milk intakes and 25-hydroxyvitamin D [25(OH)D] status and bone mineral content (BMC) and bone mineral density (BMD) in Spanish adolescents, aged 12.5-17.5 years, participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (HELENA-CSS). Bone mass was measured with dual-energy X-ray absorptiometry and diet via 2 nonconsecutive 24-h dietary recalls (n=227; 48% males). A random subsample of 101 adolescents (46% males) had available measures of 25(OH)D. Multiple linear regression was applied. Significant adjusted associations were observed in males, among milk intakes and BMC and BMD. Also in males, whole-body, head, and right arm BMD were positively related to calcium intakes. In females, 25(OH)D was positively related among others to whole-body, subtotal, and left and right arm BMC and BMD. It could be speculated that diet is not a limiting factor of bone mass development in this group of healthy adolescents, and further research on the effect of other factors in addition to diet in a larger sample should be undertaken.

Gender and age influence blood folate, vitamin B12, vitamin B6, and homocysteine levels in European adolescents: the Helena Study.

It is important to be able to evaluate vitamin status correctly at any age, but this is especially vital during adolescence since there are higher requirements for healthy growth and development. However, there are no currently available B-vitamin reference values for healthy adolescents. The aim of the present study is to assess the vitamin B status in European adolescents in order to contribute to the development of reference values for selected B-vitamins and total homocysteine (tHcy). Within the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) cross-sectional study, a sub sample of 1051 (499 males, 552 females) adolescents from ten European cities aged 12.5 to 17.49 were analyzed for fasting plasma folate (PF), red blood cell (RBC) folate, serum cobalamin (Cbl), holo-transcobalamin (Holo-TC), Vitamin B(6) (PLP), and tHcy. The level of significance was set at P < .05. Following the current cut-off for adults, 2% had low Cbl and 5% had low holo-TC concentrations. Low concentrations of both PF and RBC folate were identified in 10%. Five percent had PLP concentrations <20 nmol/L and 20% <30 nmol/L. Moreover, 5% had high tHcy; median values for the whole sample were: PF 16.0 nmol/L, RBC folate 721.9 nmol/L, Cbl 319 pmol/L, Holo-TC 57.8 pmol/L, and tHcy 6.7 μmol/L. Females had significantly higher median Cbl but lower PLP and tHcy concentrations (P < .01). THcy increased (P < .001) and PF (P < .001) concentrations decreased across age categories. Subjects showed significantly higher tHcy values at the fifth percentile of PF, corresponding with 7.5 nmol/L. Sex and age had an influence on most of the studied biomarkers and should be taken into account. The HELENA percentile distribution is consistent with data from smaller studies and could be used as reference value to characterize B-vitamin status of European adolescents.

Cardiorespiratory fitness in males, and upper limbs muscular strength in females, are positively related with 25-hydroxyvitamin D plasma concentrations in European adolescents: the HELENA study

BACKGROUND High prevalence of vitamin D insufficiency (<75 nmol/l) has been previously reported in European adolescents. Vitamin D deficiency has been related to physical fitness and adiposity but it is not clearly known whether this relationship applies to growing children and adolescents. AIM To determine how body composition and physical fitness are related to 25-hydroxyvitamin D [25(OH)D] concentrations in European adolescents. DESIGN The HEalthy Lifestyle in Europe by Nutrition in Adolescence-CSS study was a multi-centre cross-sectional study. METHODS Plasma 25(OH)D, body composition and physical fitness measures were obtained in 1006 European adolescents (470 males) aged 12.5-17.5 years. Stepwise regression and ANCOVA were performed by gender using 25(OH)D as dependent variable, with body composition, physical fitness as independent variables controlling for age, seasonality and latitude. RESULTS For males, maximum oxygen consumption (VO2max) (B = 0.189) and body mass index (BMI) (B = -0.124) were independently associated with 25(OH)D concentrations (both P < 0.05). For females, handgrip strength (B = 0.168; P < 0.01) was independently associated with 25(OH)D concentrations. Those adolescents at lower BMI and high fitness score presented significant higher 25(OH)D concentrations than those at lower fitness score in the other BMI groups (P < 0.05). CONCLUSION Cardiorespiratory fitness and upper limbs muscular strength are positively associated with 25(OH)D concentrations in male and female adolescents, respectively. Adiposity in males and low fat free mass in females are related to hypovitaminosis D. The interaction between fitness and BMI has a positive effect on 25(OH)D concentrations. Therapeutic interventions to correct the high rates of vitamin D deficiency in adolescents should consider physical fitness.

Suggestive evidence of associations between liver X receptor β polymorphisms with type 2 diabetes mellitus and obesity in three cohort studies: HUNT2 (Norway), MONICA (France) and HELENA (Europe)

BackgroundThe liver X receptors (LXR) α and β regulate lipid and carbohydrate homeostasis and inflammation. Lxrβ-/-mice are glucose intolerant and at the same time lean. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRβ and risk of type 2 diabetes mellitus (T2DM), obesity and related traits in 3 separate cohort studies.MethodsTwenty LXRβ SNPs were identified by sequencing and genotyped in the HUNT2 adult nested case-control study for T2DM (n = 835 cases/1986 controls). Five tag-SNPs (rs17373080, rs2695121, rs56151148, rs2303044 and rs3219281), covering 99.3% of the entire common genetic variability of the LXRβ gene were identified and genotyped in the French MONICA adult study (n = 2318) and the European adolescent HELENA cross-sectional study (n = 1144). In silico and in vitro functionality studies were performed.ResultsWe identified suggestive or significant associations between rs17373080 and the risk of (i) T2DM in HUNT2 (OR = 0.82, p = 0.03), (ii) obesity in MONICA (OR = 1.26, p = 0.05) and (iii) overweight/obesity in HELENA (OR = 1.59, p = 0.002). An intron 4 SNP (rs28514894, a perfect proxy for rs17373080) could potentially create binding sites for hepatic nuclear factor 4 alpha (HNF4α) and nuclear factor 1 (NF1). The C allele of rs28514894 was associated with ~1.25-fold higher human LXRβ basal promoter activity in vitro. However, no differences between alleles in terms of DNA binding and reporter gene transactivation by HNF4α or NF1 were observed.ConclusionsOur results suggest that rs17373080 in LXRβ is associated with T2DM and obesity, maybe via altered LXRβ expression.