Olli J. Heinonen

Altered intracellular processing and release of neuropeptide Y due to leucine 7 to proline 7 polymorphism in the signal peptide of preproneuropeptide Y in humans.

SPECIFIC AIMSTo study the functional role of the recently found leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of preproneuropeptide Y, sympathetic responses, including neurope...

Ideal Cardiovascular Health in Adolescence Effect of Lifestyle Intervention and Association With Vascular Intima-Media Thickness and Elasticity (The Special Turku Coronary Risk Factor Intervention Project for Children [STRIP] Study)

Background— In the Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) study, repeated dietary counseling introduced in infancy and maintained until 20 years of age has led to lower intakes of saturated fat and serum low-density lipoprotein cholesterol. In this study, we examined prospectively the intervention effects on the ideal cardiovascular health concept recently described by the American Heart Association. Additionally, we investigated the association between the concept and vascular intima-media thickness and elasticity in adolescence. Methods and Results— In adolescents participating in the longitudinal, randomized, atherosclerosis-prevention STRIP study, complete data on ideal cardiovascular health metrics were available at 15 (n=394), 17 (n=376), and 19 (n=298) years of age. Aortic intima-media thickness and elasticity were measured with ultrasonography at the same ages. None of the adolescents had all 7 ideal cardiovascular health metrics. At least 5 ideal metrics was found in 60.2%, 45.5%, and 34.2% of the adolescents at 15, 17, and 19 years of age, respectively. Adolescents in the control group had an increased risk of low ideal cardiovascular health (⩽3 metrics) compared with the intervention adolescents (risk ratio=1.35; 95% confidence interval=1.04–1.77). The number of ideal cardiovascular health metrics was inversely associated with aortic intima-media thickness (P<0.0001) and directly associated with elasticity (P=0.045). The risk of having high intima-media thickness (>85th percentile) was nearly 2-fold in adolescents with a low number of metrics (⩽3) compared with those with a higher score (risk ratio=1.78; 95% confidence interval=1.31–2.43). Conclusions— Ideal cardiovascular health as determined by the AHA can be promoted in adolescents. The ideal cardiovascular health concept is beneficially associated with vascular health already in adolescence, supporting the relevance of targeting these metrics as part of primordial prevention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00223600Background —In the STRIP study, repeated dietary counseling introduced in infancy and maintained until age 20 has led to lower intakes of saturated fat and serum LDL-cholesterol. In this study, we examined prospectively the intervention effects on the ideal cardiovascular health concept recently described by the AHA. Additionally, we investigated association of the concept with vascular intima-media thickness (IMT) and elasticity in adolescence. Methods and Results —In adolescents participating in the longitudinal, randomized atherosclerosis prevention STRIP study, complete data on ideal cardiovascular health metrics were available at age 15 (n=394), 17 (n=376) and 19 (n=298). Aortic IMT and elasticity were measured with ultrasonography at same ages. None of the adolescents had all 7 ideal cardiovascular health metrics. At least 5 ideal metrics was found in 60.2%, 45.5% and 34.2% of the adolescents at age 15, 17 and 19, respectively. Adolescents in the control group had an increased risk of low ideal cardiovascular health (≤3 metrics) compared with the intervention adolescents (RR=1.35, 95%CI=1.04-1.77). Number of the ideal cardiovascular health metrics was inversely associated with aortic IMT (p 85 th percentile) was nearly two fold in adolescents with low number of the metrics (≤3) compared with those with a higher score (RR=1.78, 95%CI=1.31-2.43). Conclusions —Ideal cardiovascular health as determined by the AHA can be promoted in adolescents. The ideal cardiovascular health concept is beneficially associated with vascular health already in adolescence supporting the relevance of targeting these metrics as part of primordial prevention. Clinical Trial Registration Information —ClinicalTrials.gov, STRIP19902010. Unique Identifier: NCT00223600.

Association of Physical Activity With Vascular Endothelial Function and Intima-Media Thickness A Longitudinal Study in Adolescents

Background— Impairment of vascular endothelial function and increased intima-media thickness (IMT) are important early steps in atherogenesis. Longitudinal data on the effect of physical activity on endothelial function and IMT in healthy adolescents are lacking. We investigated prospectively the association of leisure-time physical activity with endothelial function (brachial artery flow-mediated dilatation; FMD) and aortic IMT in adolescents. Methods and Results— FMD and IMT were measured with ultrasonography at 13 (n=553), 15 (n=531), and 17 (n=494) years of age in adolescents participating in a longitudinal atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children). Mean aortic IMT, maximum FMD, and total FMD response (area under the dilatation curve 40 to 180 seconds after hyperemia) were calculated. Leisure-time physical activity was assessed with a questionnaire, and metabolic equivalent (MET) hours per week of leisure-time physical activity were calculated by multiplying weekly mean exercise intensity, duration, and frequency. Leisure-time physical activity was directly associated with endothelial function (P for maximum FMD=0.0021, P for total FMD response=0.0036) and inversely with IMT (P=0.011) after adjustment for age, sex, body mass index, high-density lipoprotein/total cholesterol, systolic blood pressure, and C-reactive protein and regarding FMD brachial artery diameter. Sedentary adolescents who increased their leisure-time physical activity from <5 to >5 (IMT) or >30 (maximum FMD) MET h/wk between 13 and 17 years of age had an increased maximum FMD (P=0.031) and decreased progression of IMT (P=0.047) compared with adolescents who remained sedentary. IMT progression was attenuated in persistently active adolescents compared with those who became sedentary (P=0.0072). Conclusions— Physical activity is favorably associated with endothelial function and IMT in adolescents. Importantly, a moderate increase in physical activity is related to decreased progression of IMT. A physically active lifestyle seems to prevent the development of subclinical atherosclerotic vascular changes in healthy adolescents. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00223600 (STRIP19902010).

Carnitine and Physical Exercise

SummaryCarnitine plays a central role in fatty acid (FA) metabolism. It transports long-chain fatty acids into mitochondria for β-oxidation. Carnitine also modulates the metabolism of coenzyme-A (CoA).It is not surprising that the use of supplementary carnitine to improve physical performance has become widespread in recent years, although there is no unequivocal support to this practice. However, critical reflections and current scientific-based knowledge are important because the implications of reduced or increased carnitine concentrations in vivo are not thoroughly understood.Several rationales have been forwarded in support of the potential ergogenic effects of oral carnitine supplementation. However the following arguments derived from established scientific observations may be forwarded: (i) carnitine supplementation neither enhances FA oxidation in vivo nor spares glycogen or postpones fatigue during exercise. Carnitine supplementation does not unequivocally improve performance of athletes; (ii) carnitine supplementation does not reduce body fat or help to lose weight; (iii) in vivo pyruvate dehydrogenase complex (PDC) is fully active already after a few seconds of intense exercise. Carnitine supplementation induces no further activation of PDC in vivo; (iv) despite an increased acetyl-CoA/free CoA ratio, PDC is not depressed during exercise in vivo and therefore supplementary carnitine has no effect on lactate accumulation; (v) carnitine supplementation per se does not affect the maximal oxygen uptake (V̇O2max); (vi) during exercise there is a redistribution of free carnitine and acylcarnitines in the muscle but there is no loss of total carnitine. Athletes are not at risk for carnitine deficiency and do not have an increased need for carnitine.Although there are some theoretical points favouring potential ergogenic effects of carnitine supplementation, there is currently no scientific basis for healthy individuals or athletes to use carnitine supplementation to improve exercise performance.

Influence of Physical Activity on Ultrasound and Dual-Energy X-ray Absorptiometry Bone Measurements in Peripubertal Girls: A Cross-Sectional Study

Abstract. The aim of this cross-sectional study was to investigate whether two types of physical exercise affect the growing skeleton differently. We used calcaneal quantitative ultrasound measurements (QUS) and dual-energy X-ray absorptiometry (DXA) for measurement of bone mineral density (BMD), and to test how QUS values reflect the axial DXA values in these various study groups. A total of 184 peripubertal Caucasian girls aged 11–17 years (65 gymnasts, 63 runners, and 56 nonathletic controls) were studied. Weight, height, stage of puberty, years of training, and the amount of leisure-time physical activity were recorded. Broadband ultrasound attenuation (BUA) and sound of speed (SOS) through the calcaneus were measured. The BMD of the femoral neck and the lumbar spine were measured by DXA. The differences in mean values of bone measurements among each exercise group were more evident in pubertal than prepubertal girls. The mean BUA and SOS values of the pubertal gymnasts were 13.7% (77.8 dB/MHz versus 68.4 dB/MHz, P < 0.05) and 2.2% (1607.7 m/s versus 1572.4 m/s, P < 0.001) higher than of the controls, respectively. The mean BMD of the femoral neck in the pubertal gymnasts and runners was 20% (0.989 g/cm2 versus 0.824 g/cm2, P < 0.001) and 9.0% (0.901 g/cm2 versus 0.824 g/cm2, P < 0.05) higher than in the controls, respectively. The amount of physical activity correlated weakly but statistically significantly with all measured BMD and ultrasonographic values in the pubertal group (r = 0.19–0.35). The correlation between ultrasonographic parameters and BMD were weak, but significant among pubertal runners (r = 0.47–0.55) and controls (r = 0.39–0.42), whereas the DXA values of the femoral neck and the ultrasonographic parameters of the calcaneus did not correlate among highly physically active gymnasts. By stepwise regression analysis, physical activity accounted for much more of the variation in the DXA values than the ultrasonographic values. We conclude that the beneficial influence of exercise on bone status as measured by ultrasound and DXA was evident in these peripubertal girls. In highly active gymnasts the increase of the calcaneal ultrasonographic values did not reflect statistically significantly the BMD values of the femoral neck.

Insulin Signalling and Resistance in Patients with Chronic Heart Failure

We investigated whether insulin resistance in patients with chronic heart failure (CHF) is associated with impaired insulin signalling in skeletal muscle and whether exercise training would lead to an improvement in insulin signalling, concomitant with enhanced insulin action. Fourteen men with CHF due to idiopathic dilated cardiomyopathy, with mild‐to‐moderate limitation of physical activity and a left‐ventricular ejection fraction of less than 45 %, were studied before and after either a 5 month exercise training programme (n= 7) or standard care (n= 7). Seven healthy men participated as controls. Whole‐body insulin‐stimulated glucose uptake was determined by the euglycaemic hyperinsulinaemic clamp technique and skeletal muscle biopsy samples were obtained before and after the insulin infusion for insulin signalling measurements. Insulin‐stimulated glucose uptake was 20 % lower in CHF patients versus healthy subjects. Physiological hyperinsulinaemia increased tyrosine phosphorylation of insulin receptor substrate (IRS)‐1 by ≈2.5‐fold, IRS‐1‐associated phosphatidylinositol 3‐kinase (PI‐3‐kinase) activity by ≈2‐fold and Akt (protein kinase B) phosphorylation by ≈3‐fold, with similar responses between healthy subjects and CHF patients. Insulin‐mediated glucose uptake was not altered in patients after standard care, whereas exercise training elicited a 25 % increase in glucose uptake. Neither standard care nor exercise training altered insulin‐stimulated tyrosine phosphorylation of IRS‐1, IRS‐1‐associated PI‐3‐kinase activity or Akt phosphorylation. In conclusion, the CHF patients demonstrated impaired insulin‐stimulated glucose uptake, despite normal signal transduction in skeletal muscle at the level of IRS‐1, PI‐3‐kinase and Akt. Of clinical relevance is the finding that exercise training improves glucose uptake. However, these changes in insulin action after exercise training appear to be independent of enhanced insulin signalling at the level of IRS‐1, PI‐3‐kinase or Akt.

Vascular Endothelial Function and Leisure-Time Physical Activity in Adolescents

Background— Exercise training improves endothelial function in high-risk adolescents, but the influence of habitual leisure-time physical activity on endothelial function in healthy adolescents is unknown. Methods and Results— Brachial artery flow-mediated endothelial function and physical activity habits were assessed in 483 adolescents (13 years of age) participating in an atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children [STRIP]). Endothelial function was examined with ultrasound; physical activity was assessed with self-administered questionnaires. A leisure-time physical activity index was calculated by multiplying mean weekly leisure-time exercise intensity, duration, and frequency [boys, 31.2±23.0 MET h/wk (mean±SD); girls, 24.0±20.9 MET h/wk; P for gender difference=0.0003]. Maximum flow-mediated dilatation (FMD) and total FMD response (the area under the dilatation curve 40 to 180 seconds after hyperemia) were calculated. In boys, maximum FMD and area under the dilatation curve 40 to 180 seconds after hyperemia were directly associated with leisure-time physical activity index in regression analyses adjusted for brachial artery diameter (maximum FMD, P=0.020; area under the dilatation curve 40 to 180 seconds after hyperemia, P=0.0055). These associations remained significant after further adjustments for body mass index, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and systolic blood pressure. A difference of ≈50 MET h/wk corresponding to ≈10 hours of moderate intensity activity weekly between sedentary and active boys was associated with an ≈1% unit difference in maximum FMD. Conclusions— Leisure-time physical activity is directly associated with brachial artery FMD responses in 13-year-old boys, providing evidence that physical activity beneficially influences endothelial function in healthy male adolescents. Lack of association in girls may reflect their overall lower physical activity level.

Physical activity and bone mineral acquisition in peripubertal girls

The association of the amount and type of physical activity with bone mineral acquisition was studied in 191 peripubertal Caucasian girls aged 9–16 years (66 gymnasts, 65 runners, and 60 nonathletic controls). Weight, height, stage of puberty, the amount of leisure‐time physical activity, and years of training were recorded, and dietary calcium and vitamin D were assessed by a semi‐quantitative questionnaire. The bone area, the bone mineral density (BMD), and the bone mineral content (BMC) of the femoral neck, lumbar spine and antebrachium were measured by dual‐energy x‐ray absorptiometry. The unadjusted mean values of BMD at the femoral neck were 15.2% higher in the pubertal gymnasts than in the controls (P<0.001). Compared with the controls, the mean BMC adjusted for bone area of the pubertal gymnasts at the femoral neck and lumbar spine was 16.4% and 10.8% higher, respectively. When comparing the association of the type of physical activity among the pubertal athletics by multiple regression analysis, height, physical activity, gymnastics, and Tanner stage emerged as significant variables and accounted for 54.7% and 63.4% of the total variation in BMD of the femoral neck and lumbar spine, respectively. These results indicate that physical activity is associated with bone mineral acquisition in peripubertal girls and that high‐impact weight‐bearing exercise seems to be particularly associated with the increase of the BMD at the femoral neck.

Increased physical activity decreases hepatic free fatty acid uptake : a study in human monozygotic twins

Exercise is considered to be beneficial for free fatty acid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity‐independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 ± 10% higher (P < 0.001) compared to the less active brothers with lower physical activity. Low‐intensity knee‐extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 ± 4.3 versus 9.0 ± 6.1 μmol (100 ml)−1 min−1, P= 0.04). Hepatic FFA uptake associated significantly with body fat percentage (P= 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal‐weighted healthy young adult men. Further, increased physical activity together with decreased intra‐abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake.

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.