Pia Salo

Prospective randomised trial in 1062 infants of diet low in saturated fat and cholesterol

Interventions to avoid atherosclerosis might be more successful if launched early in life when eating and life-style patterns are formed, but dietary interventions have been limited by fears of diet-induced growth failure. We investigated the effects of a diet low in saturated fat and cholesterol on serum lipid concentrations and growth in 1062 healthy 7-month-old infants in a randomised study. Every 1-3 months, families in the intervention group received dietary advice aimed at adequate energy supply, with low fat intake (30-35% energy, polyunsaturated/monounsaturated/saturated fatty acid ratio 1/1/1, and cholesterol intake < 200 mg daily). Infants in control families consumed an unrestricted diet. 3-day food records were collected at ages 8 and 13 months. Growth was carefully monitored. Between 7 and 13 months serum cholesterol and non-high-density-lipoprotein cholesterol concentrations did not change significantly in the intervention group (mean change -0.03 [SD 0.72] mmol/L and 0.01 [0.67] mmol/L) but increased substantially in the control group (0.24 [0.64] mmol/L and 0.23 [0.60] mmol/L; p for difference in mean changes between groups < 0.001). Daily intakes of energy and saturated fat were lower in the intervention than in the control group at 13 months (4065 [796] vs 4370 [748] kJ, p = 0.033, and 9.3 [3.5] vs 14.5 [4.8] g, p < 0.001, respectively), and intake of polyunsaturated fat was higher (5.8 [2.2] vs 4.4 [1.4] g, p < 0.001). Growth did not differ between the groups and was as expected for children at this age. Serum cholesterol concentrations fell significantly in parents of intervention-group infants. The increases in serum cholesterol and non-high-density-lipoprotein cholesterol concentration that occur in infants between the ages of 7 and 13 months can be avoided by individualised diets, with no effect on the childrens growth.

Special Turku Coronary Risk Factor Intervention Project for Babies (STRIP)

BACKGROUND Introducing nutritional and lifestyle principles to children in late infancy may permanently improve their adherence to a low-saturated fat, low-cholesterol diet, thus reducing of coronary risk factors, but worries about possible effects on growth and development have hampered such an approach. OBJECTIVE The Special Turku Coronary Risk Factor Intervention Project for Babies (STRIP) aimed to decrease exposure to known environmental atherosclerosis risk factors in children 7-36 mo of age. DESIGN Repeated, individualized counseling aimed at promoting a fat intake of 30% of energy and a 1:1:1 ratio of saturated to monounsaturated to polyunsaturated fat intake was provided (n = 540 intervention children; 284 boys). Nutrition was discussed superficially with the families of the control children (n = 522; 266 boys) and food intake was recorded at 3-6-mo intervals by use of 3-4-d food diaries. Serum lipids were measured at 6-12-mo intervals and growth was monitored regularly. RESULTS Fat intake of the intervention (control) children provided 29.5% (29.4%) of energy at the age of 8 mo, 26.6% (28.5%) of energy at 13 mo, 30.5% (33.5%) of energy at 24 mo, and 31. 5% (33.5%) of energy at 36 mo. The intervention children consistently consumed less saturated fat than did the control children (P: <0.0001). Recommended intakes of other nutrients (except vitamin D and occasionally iron) were reached irrespective of the amount and type of dietary fat. Serum cholesterol, non-HDL cholesterol, and HDL-cholesterol concentrations were 3-6% lower in the intervention children than in the control children. The intervention had no effect on height, weight, or head circumference gain. Fat intake did not predict childrens growth patterns. CONCLUSION Repeated, individualized counseling in early childhood aimed at reducing consumption of saturated fat and cholesterol was effective and feasible and did not restrict growth in circumstances in which children were regularly monitored.

Long-term consumption of plant stanol and sterol esters, vascular function and genetic regulation.

Polymorphisms of the ABCG5 and ABCG8 genes interfere with cholesterol absorption and synthesis. We determined whether common polymorphisms of these genes regulate the responses of serum cholesterol and vascular function during long-term inhibition of cholesterol absorption. Mildly to moderately hypercholesterolaemic subjects (n 282) completed a 1-year study consuming plant stanol or sterol ester (2 g stanol or sterol) or control spread. Serum cholesterol and non-cholesterol sterols, markers of cholesterol absorption and synthesis, and variables of vascular function and structure were analysed in relation to common polymorphisms of ABCG5 and ABCG8. At baseline, subjects with the 54K allele of ABCG8 had higher brachial endothelial-dependent flow-mediated dilatation than those without it (5.79 (se 0.31) v. 4.46 (se 0.44) %; P = 0.049), and subjects with the 632V allele of ABCG8 had larger brachial artery diameter than those without it. Polymorphisms of ABCG5 and ABCG8 were neither associated with serum cholesterol reduction nor changes in cholesterol metabolism or in vascular function. However, in subjects with the 400K allele of ABCG8, intima media thickness (IMT) was increased in all groups more than in those without it (P < 0.05). In conclusion, serum cholesterol lowering with absorption inhibition was not associated with polymorphic sites of ABCG5 and ABCG8. However, regulation of baseline cholesterol metabolism and vascular function and structure, and IMT progression during 1 year seemed to share some of the common polymorphic sites of these genes, suggesting a gene-regulated interaction between cholesterol metabolism and vascular function and structure.

Plant stanol ester consumption and arterial elasticity and endothelial function

We evaluated whether plant stanol esters mixed with different vegetable oil spreads improved arterial health. A total of 200 adults with serum cholesterol >5 mmol/l were randomised to consume camelina, rapeseed or sunflower oil spread with stanol (2 g/d) ester or sunflower oil spread without stanol ester (controls) for 3 months. Non-invasive ultrasound was used to measure carotid artery compliance (CAC) and brachial artery flow-mediated endothelial dependent vasodilatation (FMD) at baseline and after the intervention as markers of arterial health. Plant stanol esters reduced LDL-cholesterol by 9 % compared with controls (P < 0.001) similarly in the different treatment groups. In the combined treatment groups (n 147), CAC or FMD were not changed from controls (n 47). In a subgroup analysis, division of subjects at baseline into below and over sex-specific 50th percentiles of CAC and FMD revealed that low CAC was improved from 1.23 to 1.59 % per 10 mmHg in the treatment group (n 69), and from 1.42 to 1.47 % per 10 mmHg in controls (n 25), (P = 0.0035 between groups). Low FMD was improved from 6.9 % to 8.6 % in the treatment group (n 73) and from 6.6 % to 6.8 % in controls (n 24) (P = 0.05 between groups). In the respective high-median groups, CAC and FMD were not changed in spite of significantly lowered LDL-cholesterol. In conclusion, consumption of plant stanol ester for 3 months had no overall significant effect on arterial elasticity and endothelial function. A controlled study is needed to test whether beneficial changes are obtained in subjects with initially reduced arterial elasticity and endothelial function.

Cholesterol measurement by reflotron dry chemistry in infants, children and adults

Cholesterol values measured with the Reflotron dry chemistry (Boehringer Mannheim, Mannheim, Germany) and enzymatic (CHOD-PAP) routine method in 4150 venous blood samples from 580 infants aged 7 months, 1778 children aged 13 months to 19 years, and 1792 adults aged 18-63 years showed good correlation between the two assay systems (r > 0.92). However, the mean cholesterol concentrations were 4.5%, 3.7% and 2.3% lower in infants, children and adults, respectively, if measured with the Reflotron analyser as compared with values obtained with the CHOD-PAP method. These differences in the values were greater when cholesterol values were low (significance for the slope of regression line, p < 0.001). Values were below the detection limit of the Reflotron assay (2.59 mmol l-1) in 104 (4.4%) and 4 (0.2%) of all paediatric and adult samples, respectively. When measured with the CHOD-PAP method, 75 (72%) and 3 (75%) of these same samples showed values which exceeded the 2.59 mmol l-1 detection limit. We conclude that Reflotron dry chemistry analyser is precise in fast measurement of serum cholesterol both in all paediatric subjects and adults. A particular problem in paediatric age groups is that about 4% of children have values below the detection limit of the Reflotron analyser.

Left Ventricular Mass and Geometry in Adolescence Early Childhood Determinants

It is not known whether birth weight and early childhood growth are associated with the development of cardiac left ventricular mass (LVM) in healthy adolescents. Left ventricular growth and geometric remodeling may have long-term consequences on cardiovascular health later in life. We studied the determinants of LVM and patterns of geometric remodeling in adolescents with specific emphasis on birth size and growth in early childhood. Left ventricular measurements were obtained with echocardiography in 418 adolescents at the age of 15 years in a prospective atherosclerosis prevention study, Special Turku Coronary Risk Factor Intervention Project (STRIP). Birth weight (P=0.0004), current pulse pressure (P=0.013), physical activity level (P=0.0024), weight (P<0.0001), and male sex (P<0.001) had an independent direct association with LVM in adolescents explaining 47% of the variation. Growth in early childhood was not associated with LVM in adolescents. Birth weight (P=0.0066), current weight (P<0.0001), and physical activity level (P=0.0017) were directly associated with left ventricular posterior wall thickness. Current weight was also directly associated with septal thickness (P<0.0001). Boys had a thicker septum than girls (P=0.0092). Normal relative wall thickness and increased left ventricular mass index (eccentric remodeling) (P<0.0001), as well as increase in both variables (concentric, increased LVM) (P=0.0003), were associated with higher body mass index. Our results indicate that birth weight has a long-lasting impact on LVM and normal body weight is beneficial for cardiac structure in adolescents.

Distensibility of the Aorta and Carotid Artery and Left Ventricular Mass From Childhood to Early Adulthood

Abstract—In adults, arterial distensibility decreases with age and relates to changes in cardiac left ventricular mass. Longitudinal data on changes in arterial distensibility from childhood to adulthood are lacking. Our aim was to study the effect of age and sex, and low-saturated fat dietary counseling on arterial distensibility from childhood to early adulthood. In addition, we assessed the association of arterial distensibility with left ventricular mass. Distensibility of the abdominal aorta and common carotid artery was measured repeatedly at ages 11, 13, 15, 17, and 19 years (n=395–472) in an atherosclerosis prevention trial (Special Turku Coronary Risk Factor Intervention Project [STRIP]). Aortic and carotid distensibility decreased with age (both P<0.0001). In boys, distensibility values were generally lower (P<0.0001) and showed steeper decrease by age (age and sex interaction: both P<0.01). The low-saturated fat dietary counseling given in STRIP was not significantly associated with arterial distensibility. Left ventricular mass increased with age (P<0.0001), and it was greater in boys (P<0.0001). In conclusion, a marked age-related decrease in vascular distensibility was found already at this young age, and this decrease was more pronounced in boys than girls. The longitudinal progression of aortic and carotid distensibility was related with changes in left ventricular mass. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00223600.

Serum cholesterol-lowering efficacy of stanol ester incorporated in gelatin capsules

Background: The cholesterol-lowering properties of plant sterols have been known since the 1950s. In most clinical studies the efficacy of plant stanol ester has been studied when incorporated into mayonnaise, regular or low-fat spreads or yoghurt. Objective: The purpose of this study was to confirm the cholesterol-lowering efficacy of plant stanol ester when incorporated in capsules as part of a normal everyday diet. Design: The study had a randomized double-blind parallel design with an intervention period of 3 weeks. Forty-two subjects were randomized to receive either the active capsule (2 g of stanol) or the placebo capsule. Results: Stanol ester capsules effectively decreased the low-density lipoprotein (LDL)-cholesterol level by 8.5% [95% confidence interval (CI) 4.1 to 13.0%, p<0.001 vs baseline, p<0.05 vs placebo]. Total cholesterol concentration was reduced by 4.6% (95% CI 1.3 to 8.0%, p<0.01) and the apolipoprotein B level by 6.5% (95% CI 2.0 t o 11.0%, p<0.01) versus baseline. The LDL/HDL ratio was reduced by 10.6% (95% CI 5.2 to 16.0%, p<0.001) versus baseline. Conclusions: Plant stanol ester reduces LDL-cholesterol effectively, even when provided in a fat-free matrix such as capsules. Keywords: adult; cholesterol lowering; gelatin capsule; intervention; serum cholesterol; stanol ester

Low-saturated fat, low-cholesterol diet in 3-year-old children: Effect on intake and composition of trans fatty acids and other fatty acids in serum phospholipid fraction—The STRIP study☆☆☆★

OBJECTIVE We evaluated whether replacing a proportion of saturated fat with vegetable oils in the diet of young children increases trans fatty acid intake. STUDY DESIGN Dietary counseling aimed to reach a dietary fat ratio of unsaturated to saturated fat of 2:1 within a total fat intake of 30% to 35% of energy (E%). Four-day food records of 813 3-year-old children were analyzed, and serum phospholipid fatty acid compositions of 25 randomly selected intervention children and 17 control children were analyzed. RESULTS trans fatty acid intake of the intervention and control children was small (0.8 E% and 0.6 E%, respectively; P <.001). The relative content of serum phospholipid trans 18:1 was closely similar in intervention and control children (1.0% and 0.9% of all fatty acids, respectively). Trans fatty acid intake and serum trans 18:1 correlated poorly with childrens serum cholesterol and HDL cholesterol concentrations and inversely with serum phospholipid arachidonic to linoleic acid ratio (r = -0.373). CONCLUSIONS Trans fatty acid intake of children in Finland is minimal. Dietary intervention replacing saturated with unsaturated fatty acids is safe because it does not increase trans fatty acid intake or the relative content of trans fatty acids in the serum phospholipid fraction.

Fatty acid composition of serum cholesterol esters as a reflector of low-saturated-fat, low-cholesterol diet in young children: the STRIP project.

STRIP (the Special Turku coronary Risk factor Intervention Project) is an ongoing intervention trial which aims at a permanent reduction in the intake of saturated fat and cholesterol starting in childhood. A total of 75 intervention and 63 control children was studied consecutively at the ages of 7 and 13 mo, and 2, 3 and 5 y to evaluate the influence of such intervention on serum cholesterol ester (CE) fatty acid composition, a widely used biomarker of fatty acid intake. Analysis of 4‐d food records showed that total intake of fat and of saturated fat increased with age in both groups of children but was constantly lower in intervention than in control children, e.g. at the age of 5 y the mean intakes of total fat and of saturated fatty acids were 31.1 E% and 33.9 E% and 12.1 E% and 14.6E% in intervention and control children, respectively (p = 0.009 and 0.0001, respectively). Serum CE fatty acid compositions did not differ between the 2 groups at any age; the mean proportion of CE linoleic acid was 52.4% and 52.0% in 5‐y‐old intervention and control children, respectively. Correlation analysis showed, however, that the percentage of linoleic acid and of polyunsaturated fatty acids in CE reflected well the respective dietary intakes (r= 0.36; p = 0.0001 for both coefficients).