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Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects--a monozygotic twin study.

https://arctichealth.org/en/permalink/ahliterature165168
Source
PLoS One. 2007;2(2):e218
Publication Type
Article
Date
2007
Author
Kirsi H Pietiläinen
Marko Sysi-Aho
Aila Rissanen
Tuulikki Seppänen-Laakso
Hannele Yki-Järvinen
Jaakko Kaprio
Matej Oresic
Author Affiliation
Obesity Research Unit, Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
Source
PLoS One. 2007;2(2):e218
Date
2007
Language
English
Publication Type
Article
Keywords
Abdominal Fat - pathology
Adult
Body Composition
Body mass index
Diet Records
Female
Finland
Humans
Insulin Resistance
Lipids - blood
Lysophosphatidylcholines - blood
Magnetic Resonance Imaging
Male
Metabolomics
Obesity - blood - epidemiology - genetics - pathology
Smoking - epidemiology
Sphingomyelins - blood
Subcutaneous Fat - pathology
Twins, Monozygotic - genetics
Young Adult
Abstract
Both genetic and environmental factors are involved in the etiology of obesity and the associated lipid disturbances. We determined whether acquired obesity is associated with changes in global serum lipid profiles independent of genetic factors in young adult monozygotic (MZ) twins. 14 healthy MZ pairs discordant for obesity (10 to 25 kg weight difference) and ten weight concordant control pairs aged 24-27 years were identified from a large population-based study. Insulin sensitivity was assessed by the euglycemic clamp technique, and body composition by DEXA (% body fat) and by MRI (subcutaneous and intra-abdominal fat). Global characterization of lipid molecular species in serum was performed by a lipidomics strategy using liquid chromatography coupled to mass spectrometry. Obesity, independent of genetic influences, was primarily related to increases in lysophosphatidylcholines, lipids found in proinflammatory and proatherogenic conditions and to decreases in ether phospholipids, which are known to have antioxidant properties. These lipid changes were associated with insulin resistance, a pathogonomic characteristic of acquired obesity in these young adult twins. Our results show that obesity, already in its early stages and independent of genetic influences, is associated with deleterious alterations in the lipid metabolism known to facilitate atherogenesis, inflammation and insulin resistance.
Notes
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PubMed ID
17299598 View in PubMed
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Adipose co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes.

https://arctichealth.org/en/permalink/ahliterature118360
Source
BMC Med Genomics. 2012;5:61
Publication Type
Article
Date
2012
Author
Blake E Haas
Steve Horvath
Kirsi H Pietiläinen
Rita M Cantor
Elina Nikkola
Daphna Weissglas-Volkov
Aila Rissanen
Mete Civelek
Ivette Cruz-Bautista
Laura Riba
Johanna Kuusisto
Jaakko Kaprio
Teresa Tusie-Luna
Markku Laakso
Carlos A Aguilar-Salinas
Päivi Pajukanta
Author Affiliation
Department of Human Genetics, Gonda Center, Los Angeles, California, 90095-7088, USA.
Source
BMC Med Genomics. 2012;5:61
Date
2012
Language
English
Publication Type
Article
Keywords
Adipose Tissue - metabolism
Case-Control Studies
Finland
Gene Expression Profiling
Gene Expression Regulation
Gene Regulatory Networks - genetics
Genetic Loci - genetics
Genome-Wide Association Study
Humans
Immunity - genetics
Inflammation - blood - genetics
Mexico
Polymorphism, Single Nucleotide - genetics
Triglycerides - blood - genetics
Twins - genetics
Abstract
High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation.
Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher's Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network.
We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals.
This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations.
Notes
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PubMed ID
23217153 View in PubMed
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Cardiorespiratory Fitness and Adiposity as Determinants of Metabolic Health-Pooled Analysis of Two Twin Cohorts.

https://arctichealth.org/en/permalink/ahliterature285680
Source
J Clin Endocrinol Metab. 2017 May 01;102(5):1520-1528
Publication Type
Article
Date
May-01-2017
Author
Sakari Jukarainen
René Holst
Christine Dalgård
Päivi Piirilä
Jesper Lundbom
Antti Hakkarainen
Nina Lundbom
Aila Rissanen
Jaakko Kaprio
Kirsten Ohm Kyvik
Thorkild I A Sørensen
Kirsi H Pietiläinen
Source
J Clin Endocrinol Metab. 2017 May 01;102(5):1520-1528
Date
May-01-2017
Language
English
Publication Type
Article
Keywords
Adiposity - genetics - physiology
Adolescent
Adult
Aged
Body Composition - genetics - physiology
Cardiorespiratory Fitness - physiology
Cholesterol, HDL - metabolism
Cholesterol, LDL - metabolism
Cohort Studies
Cross-Sectional Studies
Denmark
Electric Impedance
Female
Finland
Gene-Environment Interaction
Glucose Tolerance Test
Humans
Insulin Resistance - genetics - physiology
Intra-Abdominal Fat - diagnostic imaging
Linear Models
Liver - diagnostic imaging
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Male
Metabolic Syndrome X - genetics - metabolism
Middle Aged
Multivariate Analysis
Oxygen Consumption - genetics - physiology
Triglycerides - metabolism
Twins, Dizygotic
Twins, Monozygotic
Young Adult
Abstract
The joint effects of cardiorespiratory fitness (CRF) and body composition on metabolic health are not well known.
To examine the associations of CRF, fat-free mass index (FFMI), and fat mass index (FMI) with metabolic health in individual twins and controlling for genetic and shared environmental effects by studying monozygotic intrapair differences.
Two cross-sectional samples of healthy adult monozygotic and dizygotic twins were drawn from population-based Danish and Finnish national twin registries (n = 996 and n = 309).
CRF was defined as VO2max divided by fat-free mass. Insulin sensitivity and acute insulin response indices were derived from an oral glucose tolerance test. A continuous metabolic syndrome score was calculated. Visceral and liver fat were measured in the Finnish sample. Associations were analyzed separately in both cohorts with multivariate linear regression and aggregated with meta-analytic methods.
Insulin sensitivity, acute insulin response, metabolic syndrome score, visceral, and liver fat amount had strong and statistically significant associations with FMI (
?
0.53 to 0.79), whereas their associations with CRF and FFMI were at most weak (
0.02 to 0.15). The results of the monozygotic intrapair differences analysis showed the same pattern.
Although FMI is strongly associated with worsening of metabolic health traits, even after controlling for genetic and shared environmental factors, there was little evidence for the effects of CRF or FFMI on metabolic health. This suggests that changing FMI rather than CRF or FFMI may affect metabolic health irrespective of genetic or early environmental determinants.
PubMed ID
28324016 View in PubMed
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The effect of alcohol consumption on later obesity in early adulthood--a population-based longitudinal study.

https://arctichealth.org/en/permalink/ahliterature146090
Source
Alcohol Alcohol. 2010 Mar-Apr;45(2):173-9
Publication Type
Article
Author
Matti Pajari
Kirsi H Pietiläinen
Jaakko Kaprio
Richard J Rose
Suoma E Saarni
Author Affiliation
Department of Public Health, University of Helsinki, PO Box 14, 00014 Helsinki, Finland.
Source
Alcohol Alcohol. 2010 Mar-Apr;45(2):173-9
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Age of Onset
Alcohol Drinking - adverse effects - epidemiology
Body mass index
Female
Finland
Health Surveys
Humans
Longitudinal Studies
Male
Obesity - epidemiology
Obesity, Abdominal - epidemiology
Risk factors
Temperance - statistics & numerical data
Waist Circumference
Young Adult
Abstract
The study aimed to determine whether alcohol use during late adolescence contributes to the weight gain from adolescence to young adulthood or risk of obesity or waist circumference at young adulthood.
A population-based, longitudinal study of 5563 Finnish twins born in 1975-1979 and surveyed at ages 16 (T1), 17 (T2), 18 (T3) and 23-27 (T4) years. Drinking habits, height and weight were self-reported at T1, T2, T3 and T4; waist circumference was self-measured at T4. As potential confounders, we used smoking, diet, physical activity, place of residence, socio-economic status and parents' body mass index (BMI).
Compared to the reference group (drinking once to twice per month), the BMI increase from T3 to T4 was less among abstaining men (-0.62 kg/m(2), (95% CI -1.04, -0.20)) and among women in those drinking less than monthly (-0.38 kg/m(2), (-0.71, -0.04)). In women, at least weekly drinking was associated with larger waist circumference (Beta 1.55 cm, (0.48, 2.61)), but this became statistically non-significant after adjusting for potential confounders. In a multilevel model for change, drinking frequency was not associated with weight change in women; in men, a negative association was seen, but it was statistically non-significant after adjusting for potential confounders.
These results from a population-based study with a large set of confounding variables suggest that alcohol use during adolescence has at most a minor effect on weight gain or development of abdominal obesity from adolescence to young adulthood.
Notes
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PubMed ID
20071348 View in PubMed
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Genetic and environmental influences on the tracking of body size from birth to early adulthood.

https://arctichealth.org/en/permalink/ahliterature188599
Source
Obes Res. 2002 Sep;10(9):875-84
Publication Type
Article
Date
Sep-2002
Author
Kirsi H Pietiläinen
Jaakko Kaprio
Maija Räsänen
Aila Rissanen
Richard J Rose
Author Affiliation
University of Helsinki, Department of Public Health, FIN-00014 Helsinki, Finland. kirsi.pietilainen@helsinki.fi
Source
Obes Res. 2002 Sep;10(9):875-84
Date
Sep-2002
Language
English
Publication Type
Article
Keywords
Adolescent
Birth weight
Body Constitution - genetics
Body Height
Body mass index
Body Weight
Environment
Female
Finland
Gestational Age
Humans
Infant, Newborn
Longitudinal Studies
Male
Models, Statistical
Questionnaires
Regression Analysis
Twins, Dizygotic
Twins, Monozygotic
Abstract
This study identified genetic and environmental influences on the tracking of body size from birth to 16 to 18.5 years of age.
Longitudinal information was collected from a nationally representative sample of Finnish twin adolescents (birth cohorts 1975 to 1979) and their parents through questionnaires mailed when the twins were ages 16 and 18.5 years old. The sample included 702 monozygotic, 724 same-sex dizygotic, and 762 opposite-sex dizygotic sets of twins. The measures used were length, weight, ponderal index (kilograms per cubic meters), and gestational age at birth, and height, weight, and body mass index (kilograms per square meters) at 16 to 18.5 years of age. The changes in genetic and environmental influences on body size from birth to early adulthood were analyzed by quantitative genetic modeling.
The twins who had a higher weight or ponderal index at birth were taller and heavier in early adulthood, whereas those who were longer at birth were taller, but not heavier, later in life. Adult height was affected more by the birth size than body mass index. In the genetic modeling analyses, the genetic factors accounting for the variation of body size became more apparent with age, and both genetic and environmental influences on stature had a sizable carry-over effect from birth to late adolescence, whereas for relative weight, the influences were more age-specific.
The genetic and environmental architecture of body size changes from birth to adulthood. Even in monozygotic twins who share their genetic background, the initially larger twin tended to remain larger, demonstrating the long-lasting effects of fetal environment on final body size.
PubMed ID
12226135 View in PubMed
Less detail

Genetic influences on physical activity in young adults: a twin study.

https://arctichealth.org/en/permalink/ahliterature128223
Source
Med Sci Sports Exerc. 2012 Jul;44(7):1293-301
Publication Type
Article
Date
Jul-2012
Author
Linda Mustelin
Jessica Joutsi
Antti Latvala
Kirsi H Pietiläinen
Aila Rissanen
Jaakko Kaprio
Author Affiliation
Hjelt Institute, Twin Research Unit, University of Helsinki, Helsinki, Finland. linda.mustelin@helsinki.fi
Source
Med Sci Sports Exerc. 2012 Jul;44(7):1293-301
Date
Jul-2012
Language
English
Publication Type
Article
Keywords
Adult
Confidence Intervals
Female
Finland
Gene-Environment Interaction
Health Behavior
Humans
Male
Molecular Epidemiology
Motor Activity - genetics
Quantitative Trait, Heritable
Questionnaires
Young Adult
Abstract
The aim of this study was to investigate genetic and environmental influences on different aspects of physical activity in young adult twins.
We studied 1274 Finnish twins with a mean age of 22.4 yr, from the population-based FinnTwin12 study. Physical activity was assessed with the Baecke Questionnaire, yielding four indexes: the sport index, leisure time activity index, work index, and total score. Quantitative genetic analyses based on linear structural equations were used to estimate the contribution of genetic and environmental factors on these physical activity traits.
The overall heritability estimates were 64% (95% confidence interval (CI) = 0.56%-0.70%) for sports activity, 41% (95% CI = 0.31%-0.51%) for leisure time activity excluding sports, 56% (95% CI = 0.48%-0.63%) for physical activity at work, and 54% (95% CI = 0.45%-0.62%) for total physical activity. Unique environmental factors accounted for the rest of the trait variances. We did not find evidence for common environmental or dominant genetic influences. The heritability estimates did not differ between men and women, and no sex-specific genetic factors were found. Sports activity and leisure time activity excluding sports were associated (r = 0.27), and additive genetic factors explained 57% of their association.
Our results suggest that genetic factors contribute significantly to physical activity levels in young adults and that sports activity is under stronger genetic influence than leisure time physical activity excluding sports. We also concluded that physical activity at work does not seem to be associated with sports activities or other leisure time physical activity at this age.
PubMed ID
22217564 View in PubMed
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Genome-wide association study identifies multiple loci influencing human serum metabolite levels.

https://arctichealth.org/en/permalink/ahliterature127530
Source
Nat Genet. 2012 Mar;44(3):269-76
Publication Type
Article
Date
Mar-2012
Author
Johannes Kettunen
Taru Tukiainen
Antti-Pekka Sarin
Alfredo Ortega-Alonso
Emmi Tikkanen
Leo-Pekka Lyytikäinen
Antti J Kangas
Pasi Soininen
Peter Würtz
Kaisa Silander
Danielle M Dick
Richard J Rose
Markku J Savolainen
Jorma Viikari
Mika Kähönen
Terho Lehtimäki
Kirsi H Pietiläinen
Michael Inouye
Mark I McCarthy
Antti Jula
Johan Eriksson
Olli T Raitakari
Veikko Salomaa
Jaakko Kaprio
Marjo-Riitta Järvelin
Leena Peltonen
Markus Perola
Nelson B Freimer
Mika Ala-Korpela
Aarno Palotie
Samuli Ripatti
Author Affiliation
Institute for Molecular Medicine Finland, University of Helsinki, Finland.
Source
Nat Genet. 2012 Mar;44(3):269-76
Date
Mar-2012
Language
English
Publication Type
Article
Keywords
Amino Acids - metabolism
Analysis of Variance
Finland
Genome-Wide Association Study
Genotype
Humans
Inheritance Patterns - genetics
Lipid Metabolism - genetics
Magnetic Resonance Spectroscopy
Metabolome
Phenotype
Polymorphism, Single Nucleotide - genetics
Quantitative Trait Loci - genetics
Serum - metabolism
Abstract
Nuclear magnetic resonance assays allow for measurement of a wide range of metabolic phenotypes. We report here the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes assessed by NMR of serum samples. We identified significant associations (P
Notes
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PubMed ID
22286219 View in PubMed
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Habitual dietary intake is associated with stool microbiota composition in monozygotic twins.

https://arctichealth.org/en/permalink/ahliterature116968
Source
J Nutr. 2013 Apr;143(4):417-23
Publication Type
Article
Date
Apr-2013
Author
Catarina D Simões
Johanna Maukonen
Jaakko Kaprio
Aila Rissanen
Kirsi H Pietiläinen
Maria Saarela
Author Affiliation
VTT Technical Research Centre of Finland, Espoo, Finland. catarina.simoes@helsinki.fi
Source
J Nutr. 2013 Apr;143(4):417-23
Date
Apr-2013
Language
English
Publication Type
Article
Keywords
Adult
Bacterial Load
Bacteroides - genetics
Bifidobacterium - genetics
Body Composition
Body mass index
Clostridium
DNA, Bacterial - analysis - isolation & purification
Denaturing Gradient Gel Electrophoresis
Diet
Dietary Fats, Unsaturated - administration & dosage
Dietary Fiber - administration & dosage
Energy intake
Eubacterium - genetics
Feces - microbiology
Female
Finland
Food Habits - physiology
Humans
Lactobacillus - genetics
Male
Obesity - microbiology
Overweight - microbiology
Polymerase Chain Reaction
RNA, Ribosomal, 16S - analysis
Twins, Monozygotic - genetics
Abstract
The impact of diet on the gut microbiota has usually been assessed by subjecting people to the same controlled diet and thereafter following the shifts in the microbiota. In the present study, we used habitual dietary intake, clinical data, quantitative polymerase chain reaction, and denaturing gradient gel electrophoresis (DGGE) to characterize the stool microbiota of Finnish monozygotic twins. The effect of diet on the numbers of bacteria was described through a hierarchical linear mixed model that included the twin individuals, stratified by body mass index, and their families as random effects. The abundance and diversity of the bacterial groups studied did not differ between normal-weight, overweight, and obese individuals with the techniques used. Intakes of energy, monounsaturated fatty acids, n3 polyunsaturated fatty acids (PUFAs), n6 PUFAs, and soluble fiber had significant associations with the stool bacterial numbers (e.g., increased energy intake was associated with reduced numbers of Bacteroides spp.). In addition, co-twins with identical energy intake had more similar numbers and DGGE-profile diversities of Bacteroides spp. than did the co-twins with different intake. Moreover, the co-twins who ingested the same amounts of saturated fatty acids had very similar DGGE profiles of Bacteroides spp., whereas the co-twins with similar consumption of fiber had a very low bifidobacterial DGGE-profile similarity. In conclusion, our findings confirm that the diet plays an important role in the modulation of the stool microbiota, in particular Bacteroides spp. and bifidobacteria.
PubMed ID
23343669 View in PubMed
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Increased coagulation factor VIII, IX, XI and XII activities in non-alcoholic fatty liver disease.

https://arctichealth.org/en/permalink/ahliterature138835
Source
Liver Int. 2011 Feb;31(2):176-83
Publication Type
Article
Date
Feb-2011
Author
Anna Kotronen
Lotta Joutsi-Korhonen
Ksenia Sevastianova
Robert Bergholm
Antti Hakkarainen
Kirsi H Pietiläinen
Nina Lundbom
Aila Rissanen
Riitta Lassila
Hannele Yki-Järvinen
Author Affiliation
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland. anna.kotronen@helsinki.fi
Source
Liver Int. 2011 Feb;31(2):176-83
Date
Feb-2011
Language
English
Publication Type
Article
Keywords
Adult
Age Factors
Aged
Body mass index
Factor IX - metabolism
Factor VIII - metabolism
Factor XI - metabolism
Factor XII - metabolism
Fatty Liver - blood - metabolism
Female
Fibrinogen - metabolism
Finland
Humans
Insulin Resistance - physiology
Magnetic Resonance Spectroscopy
Male
Middle Aged
Partial Thromboplastin Time
Prothrombin - metabolism
Sex Factors
von Willebrand Factor - metabolism
Abstract
Obesity and the metabolic syndrome are established risk factors of venous thromboembolism. As most coagulation factors are produced exclusively by the liver and non-alcoholic fatty liver disease (NAFLD) is tightly related to metabolic disorders, we aimed at studying the association of liver fat with various coagulation factor activities.
Plasma prothrombin (PT) and activated partial thromboplastin time, activities of vWF:RCo, FVII, FVIII, FIX, FXI, FXII, FXIII, fibrinogen and D-dimer concentrations were measured in 54 subjects with and 44 without NAFLD diagnosed by proton magnetic resonance spectroscopy. Subjects were recruited retrospectively for metabolic studies in our laboratory. The body composition and features of insulin resistance were measured in all subjects.
FVIII (107±30 vs. 84±22%, P
PubMed ID
21134109 View in PubMed
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Leisure-time physical activity and nutrition: a twin study.

https://arctichealth.org/en/permalink/ahliterature143786
Source
Public Health Nutr. 2011 May;14(5):846-52
Publication Type
Article
Date
May-2011
Author
Mirva Rintala
Arja Lyytikäinen
Tuija Leskinen
Markku Alen
Kirsi H Pietiläinen
Jaakko Kaprio
Urho M Kujala
Author Affiliation
Department of Health Sciences, University of Jyväskylä, PO Box 35(LL), FIN-40014, Finland. mirva.l.a.rintala@jyu.fi
Source
Public Health Nutr. 2011 May;14(5):846-52
Date
May-2011
Language
English
Publication Type
Article
Keywords
Aged
Body Composition - physiology
Cross-Sectional Studies
Diet Records
Energy intake
Exercise - physiology
Feeding Behavior
Female
Finland
Food Habits
Health Behavior
Health Promotion - organization & administration
Humans
Leisure Activities
Male
Middle Aged
Nutritional Physiological Phenomena - physiology
Obesity - prevention & control
Satiation - physiology
Twins, Dizygotic - physiology
Twins, Monozygotic - physiology
Abstract
To determine the association between long-term leisure-time physical activity/inactivity and eating behaviours in twin pairs discordant for physical activity for 30 years.
Co-twin control design with cross-sectional data collection using questionnaire on eating habits and 5 d food diary. Differences in eating behaviours between physically active and inactive co-twins were analysed with pairwise tests.
Finland.
Sixteen same-sex twin pairs (seven monozygotic and nine dizygotic, mean age 60 years) discordant for physical activity, selected from the Finnish Twin Cohort on the basis of physical activity discordance for 30 years, blinded to their possible differences in eating behaviours.
The eating habits questionnaire revealed that physically active co-twins more frequently reported that it is easy to eat according to need, whereas overeating and/or restrictive eating was more common among the inactive co-twins (P = 0·035). Avoiding calories was more common among the active than inactive co-twins (P = 0·034). Based on food diaries the physically active co-twins had daily energy intake on average 15·5 kJ/kg higher than their inactive co-twins (P = 0·030). The active co-twins also had a higher intake of vitamin C (P = 0·004), total water (P = 0·044), legumes and nuts (P = 0·015) and sweets (P = 0·036), as well as a lower energy-adjusted intake of meat (P = 0·013).
The physically active persons seem to eat more but not necessarily healthier food. However, habitual physical activity may help in eating according to need and in reaching and maintaining a healthy body composition. Therefore, it is necessary to incorporate both dietary and physical activity advice into health counselling.
PubMed ID
20441664 View in PubMed
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