Achievement of the Targets of the 20-Year Infancy-Onset Dietary Intervention-Association with Metabolic Profile from Childhood to Adulthood.

The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9-19 years (n = 549-338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) < 1:2, (2) intake of SAFA < 10% of total energy intake, (3) fiber intake ≥ 80th age-specific percentile, and (4) sucrose intake ≤ 20th age-specific percentile. Metabolic biomarkers were quantified by high-throughput nuclear magnetic resonance metabolomics. Better adherence to the dietary targets, regardless of study group allocation, was assoiated with higher serum proportion of PUFAs, lower serum proportion of SAFAs, and a higher degree of unsaturation of fatty acids. Achieving ≥ 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (≥2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health.

Determinants of serum 25(OH)D concentration in young and middle-aged adults. The Cardiovascular Risk in Young Finns Study.

INTRODUCTION: We studied prevalence of hypovitaminosis D, its determinants, and whether achievement of recommended dietary vitamin D intake (10 µg/d) is associated with absence of hypovitaminosis D in adults. METHODS: The study is part of the Cardiovascular Risk in Young Finns Study. We collected serum samples of 25-hydroxyvitamin D as part of the 27-year follow-up (994 men and 1,210 women aged 30-45 years). Hypovitaminosis was defined as vitamin D concentration ≤ 50 nmol/L. RESULTS: Hypovitaminosis D was found in 38% of men and 34% of women. Dietary vitamin D intake (OR 0.90, 95% CI 0.86-0.93), use of vitamin-mineral supplements (0.66, 0.51-0.85), sunny holiday (0.55, 0.41-0.75), and oral contraceptive use in women (0.45, 0.27-0.75) were independently associated with reduced odds of hypovitaminosis. Increase in body mass index (1.06, 1.03-1.09), being a smoker (1.36, 0.97-1.92), investigation month (December versus other) (1.35, 1.12-1.61), and risk alleles in genotypes rs12785878 (1.31, 1.00-1.70) and rs2282679 (2.08, 1.66-2.60) increased odds of hypovitaminosis. Hypovitaminosis D was common also when recommended dietary intake was obtained (men 29%, women 24%). CONCLUSION: Several factors were associated with hypovitaminosis D. The condition was common even when recommended vitamin D intake was reported. The results support the importance of vitamin D fortification and nutrient supplement use.

Interactions between genetic variants and dietary lipid composition: effects on circulating LDL cholesterol in children.

BACKGROUND: Elevated serum low-density lipoprotein (LDL) cholesterol is a predictor of cardiovascular disease events, and the quality of dietary fat is known to influence serum concentrations of LDL cholesterol in children. Interindividual differences in response to diet exist, but the underlying genetic factors remain largely unknown. OBJECTIVE: We aimed to identify genetic variants that modify the variation in serum lipid response to dietary fat quality. DESIGN: We used data from 2 longitudinal Finnish cohorts designed to study risk factors for cardiovascular diseases. Large-scale genotyping was performed with Metabochip in a long-term randomized controlled dietary intervention trial, the Special Turku Coronary Risk Factor Intervention Project (STRIP), for discovery of genetic polymorphisms. The observational Cardiovascular Risk in Young Finns Study (YFS) with genome-wide genetic data was used as a replication sample for the initial findings. Dietary records were used to calculate the ratio of unsaturated to saturated fats. Interaction models and multiple follow-ups were used in the analysis. RESULTS: In the STRIP cohort, a variant within the PARK2 locus, rs9364628, showed moderate interaction with dietary fat quality and a consistent direction of effect in both scans on serum LDL-cholesterol concentration in children aged 5 and 7 y (P < 0.0084 and P < 0.0057, respectively). In the YFS cohort, we were unable to replicate the initial discovery signal, but rs12207186 within the PARK2 locus and dietary lipid quality had a stronger interaction effect on serum LDL-cholesterol concentration (P < 9.44 × 10(-5)) than did rs9364628 in children aged 6 y. CONCLUSION: This genotyping study involving 2 cohorts of healthy Finnish children indicates a possible interaction between PARK2 variants and dietary fat quality on serum LDL-cholesterol concentration. This trial was registered at clinicaltrials.gov as NCT00223600.

Effects of sea buckthorn and bilberry on serum metabolites differ according to baseline metabolic profiles in overweight women: a randomized crossover trial.

BACKGROUND: Berries are associated with health benefits. Little is known about the effect of baseline metabolome on the overall metabolic responses to berry intake. OBJECTIVE: We studied the effects of berries on serum metabolome. DESIGN: Eighty overweight women completed this randomized crossover study. During the interventions of 30 d, subjects consumed dried sea buckthorn berries (SBs), sea buckthorn oil (SBo), sea buckthorn phenolics ethanol extract mixed with maltodextrin (SBe+MD) (1:1), or frozen bilberries. Metabolic profiles were quantified from serum samples by using (1)H nuclear magnetic resonance spectroscopy. RESULTS: All interventions induced a significant (P < 0.001-0.003) effect on the overall metabolic profiles. The effect was observed both in participants who had a metabolic profile that reflected higher cardiometabolic risk at baseline (group B: P = 0.001-0.008) and in participants who had a lower-risk profile (group A: P < 0.001-0.009). Although most of the changes in individual metabolites were not statistically significant after correction for multiplicity, clear trends were observed. SB-induced effects were mainly on serum triglycerides and very-low-density lipoprotein (VLDL) and its subclasses, which decreased in metabolic group B. SBo induced a decreasing trend in serum total, intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) cholesterol and subfractions of IDL and LDL in group B. During the SBe+MD treatment, VLDL fractions and serum triglycerides increased. Bilberries caused beneficial changes in serum lipids and lipoproteins in group B, whereas the opposite was true in group A. CONCLUSION: Berry intake has overall metabolic effects, which depend on the cardiometabolic risk profile at baseline. This trial was registered at clinicaltrials.gov as NCT01860547.

Fetal growth, omega-3 (n-3) fatty acids, and progression of subclinical atherosclerosis: preventing fetal origins of disease? The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Impaired fetal growth is independently associated with an increased risk of cardiovascular events in adulthood. Prevention strategies that can be implemented during adulthood have not been identified. OBJECTIVE: The objective was to determine whether habitual omega-3 (n-3) fatty acid intake is associated with the rate of increase of carotid intima-media thickness during adulthood in individuals with impaired fetal growth. DESIGN: This was a population-based, prospective cohort study of 1573 adults in Finland. Carotid intima-media thickness was assessed in 2001 (at ages 24-39 y) and in 2007. Participants were categorized as having had impaired fetal growth (term birth with birth weight <10th percentile for sex or preterm birth with birth weight <25th percentile for gestational age and sex; n = 193) or normal fetal growth (all other participants; n = 1380). Omega-3 fatty acid intake was assessed by using a food-frequency questionnaire and on the basis of serum fatty acid concentrations. RESULTS: In multivariable models, the 6-y progression of carotid intima-media thickness was inversely associated with dietary omega-3 fatty acids in those with impaired fetal growth (P = 0.04). Similarly, serum omega-3 fatty acid concentrations were inversely associated with the 6-y progression of carotid intima-media thickness in those with impaired fetal growth (P = 0.04) but were not noted in those with normal fetal growth (P = 0.94 and P = 0.26, respectively). CONCLUSION: Dietary intake of omega-3 fatty acids is associated with a slower rate of increase in carotid intima-media thickness in those with impaired fetal growth.

Childhood serum cholesterol ester fatty acids are associated with blood pressure 27 y later in the Cardiovascular Risk in Young Finns Study.

BACKGROUND: In adults, dietary fatty acids (FAs) modify blood pressure (BP), but it is not known whether childhood FA quality is associated with adulthood BP. OBJECTIVE: The purpose of the study was to investigate links between childhood serum cholesterol ester fatty acid (CEFA) proportions and adulthood systolic blood pressure (SBP) and diastolic blood pressure (DBP). DESIGN: We examined a cohort of 803 boys and girls (aged 3-18 y at baseline in 1980 and followed for 27 y) by using regression models adjusted for the known risk factors of BP. CEFAs were analyzed as markers of dietary FA intake. RESULTS: In men, serum SFA (B = 2.97, P < 0.001 for SBP; B = 1.48, P = 0.015 for DBP), MUFA (B = 0.61, P = 0.001 for SBP; B = 0.27, P = 0.078 for DBP), and omega-3 (n-3) PUFA (B = 5.50, P < 0.001 for SBP; B = 2.47, P = 0.015 for DBP) proportions, which were derived mainly from animal fats in this population, were positively associated with BP, whereas the omega-6 (n-6) PUFA proportion, which was derived mainly from vegetable oils and margarines, was negatively associated with BP (B = -0.56, P < 0.001 for SBP; B = -0.27, P < 0.018 for DBP). Serum cholesterol ester SFA and PUFA associations were supported by dietary intake data. In women, the associations between CEFA proportions and BP were weaker [for SBP: B = 0.36, P = 0.638 (NS) for SFA; B = 0.44, P = 0.019 for MUFA; B = 1.18, P = 0.376 (NS) for n-3 PUFA; and B = -0.33, P = 0.023 for n-6 PUFA]. CONCLUSION: Our findings suggest that fat quality as reflected in the serum cholesterol ester fraction in childhood is independently associated with adulthood BP particularly in men but also, to some extent, in women.

High-throughput serum NMR metabonomics for cost-effective holistic studies on systemic metabolism.

A high-throughput proton (1H) nuclear magnetic resonance (NMR) metabonomics approach is introduced to characterise systemic metabolic phenotypes. The methodology combines two molecular windows that contain the majority of the metabolic information available by 1H NMR from native serum, e.g. serum lipids, lipoprotein subclasses as well as various low-molecular-weight metabolites. The experimentation is robotics-controlled and fully automated with a capacity of about 150-180 samples in 24 h. To the best of our knowledge, the presented set-up is unique in the sense of experimental high-throughput, cost-effectiveness, and automated multi-metabolic data analyses. As an example, we demonstrate that the NMR data as such reveal associations between systemic metabolic phenotypes and the metabolic syndrome (n = 4407). The high-throughput of up to 50,000 serum samples per year is also paving the way for this technology in large-scale clinical and epidemiological studies. In contradiction to single 'biomarkers', the application of this holistic NMR approach and the integrated computational methods provides a data-driven systems biology approach to biomedical research.

Prospective study on food fortification with vitamin D among adolescent females in Finland: minor effects.

Vitamin D insufficiency is common particularly during winter time. After the recommendation by the Ministry of Social Affairs and Health, Finnish fluid milks and margarines have been fortified with vitamin D since February 2003. The aims of the present study were to examine the impact of vitamin D fortification of food supplies on serum 25-hydroxyvitamin D (S-25(OH)D) concentrations and on daily dietary vitamin D intake among adolescent females. One hundred and forty-two girls of Caucasian ethnicity aged 12-18 years completed semi-quantitative FFQ from which the dietary vitamin D and Ca intakes were calculated. S-25(OH)D was measured by radioimmunoassay. The study was performed from February-March 2000 to February-March 2004, one year after the initiation of fortification. The mean dietary intake of vitamin D was < 7.5 microg in 91.5 % of the adolescent girls in 2000 and 83.8 % in 2004. The midwinter mean S-25(OH)D concentration did not change significantly during the follow-up period (48.3 v. 48.1 nmol/l, NS). The proportion of participants who had S-25(OH)D concentration < 50 nmol/l was 60.6 % in 2000 and 65.5 % in 2004. Only 7.0 % of the participants had an adequate S-25(OH)D ( >or= 75 nmol/l) level in 2000 or 4 years later. The vitamin D fortification of fluid milks and margarines was inadequate to prevent vitamin D insufficiency. There are numerous adolescent girls and women who are not reached by the current fortification policy. Therefore new innovative and feasible ways of improving vitamin D nutrition are urged.

Increased serum soluble transferrin receptor concentration detects subclinical iron deficiency in healthy adolescent girls.

The objective of this study was to investigate whether the measurement of serum soluble transferrin receptor could detect subclinical iron deficiency in adolescent girls, and to assess the possible specificity-compromising effects of growth, menarche, and intensive physical activity. The study population consisted of 191 physically active (control) girls aged 9-15 years. Dietary iron intake was estimated at baseline, and after 6 and 12 months. Iron status of the subjects was assessed by haematological laboratory tests at 6 and 12 months. A 3-month iron and multivitamin supplementation was started after the visit at 6 months. The supplementation consistently decreased soluble transferrin receptor concentrations in subjects with initial values greater than 2.4 mg/l, which was determined by regression analysis to be the cut-off value for iron-deficient erythropoiesis. The 95% reference interval in the iron-replete subjects (0.9-2.4 mg/l) was consistent with this finding. In our population, the incidence of subclinical iron deficiency was 10%. Growth or physical activity had no effect on the iron status. This study shows that, similarly to adults, soluble transferrin receptor measurement can be used to detect subclinical iron deficiency in adolescents (competitive athletes or normal controls). We suggest that soluble transferrin receptor concentrations above 2.4 mg/l indicate clinically relevant iron deficiency in adolescents.

Vitamin D and attainment of peak bone mass among peripubertal Finnish girls: a 3-y prospective study.

BACKGROUND: Little is known about the effect of vitamin D status on bone gain in adolescents. OBJECTIVE: The objective was to examine whether vitamin D status is associated with accrual of bone mineral density (BMD) and bone mineral apparent density (BMAD). DESIGN: This 3-y prospective study examined the association between changes in BMD or BMAD and serum 25-hydroxyvitamin D [25(OH)D] in 171 healthy Finnish girls aged 9-15 y. Lumbar spine and femoral neck BMDs were measured by dual-energy X-ray absorptiometry. RESULTS: Baseline 25(OH)D correlated significantly with the unadjusted 3-y change in BMD at the lumbar spine (r = 0.35, P < 0.001) and femoral neck (r = 0.32, P < 0.001) in all participants. The difference from baseline in adjusted 3-y BMD accumulation between those with severe hypovitaminosis D [25(OH)D < 20 nmol/L] and those with a normal vitamin D status [25(OH)D > or = 37.5 nmol/L] was 4% (12.7%, 13.1%, and 16.7% for the lowest, middle, and highest tertiles of 25(OH)D, respectively; P for trend = 0.01) at the lumbar spine in the girls with advanced sexual maturation at baseline (n = 129). Moreover, the adjusted change in lumbar spine BMD was 27% greater in the highest vitamin D intake tertile than in the lowest tertile in the same girls (P for trend = 0.016). CONCLUSIONS: Pubertal girls with hypovitaminosis D seem to be at risk of not reaching maximum peak bone mass, particularly at the lumbar spine. Dietary enrichment or supplementation with vitamin D should be considered to ensure an adequate vitamin D status.