Effects of gender, apolipoprotein E phenotype and cholesterol-lowering by plant stanol esters in children: the STRIP study. Special Turku Coronary Risk Factor Intervention Project.

AIM: To evaluate the effects of gender, apolipoprotein E phenotype and cholesterol absorption and synthesis (estimated as serum plant sterol and cholesterol precursor sterol concentrations) on the cholesterol-lowering effect of plant stanol esters in children. METHODS: Eighty-one healthy, normocholesterolaemic 6-y-old children (45 boys) were recruited from the Special Turku Coronary Risk Factor Intervention Project (STRIP), a randomized prospective trial aiming at atherosclerosis prevention in childhood. This placebo-controlled, double-blind, cross-over study comprised two 3-mo study periods and a 6-wk wash-out period. During the study periods, 20 g of the children's daily dietary fat intake was replaced with plant stanol ester margarine or control margarine. RESULTS: In boys, plant stanol esters reduced serum total and low-density lipoprotein cholesterol concentrations by 6% (0.09 to 0.42 mmol/L) and 9% (0.09 to 0.36 mmol/L), respectively (p < 0.01 for both). In girls, the decreases in concentrations were 4% (0.03 to 0.38 mmol/L) and 6% (0.02 to 0.32 mmol/l) (p < 0.05 for both). The response rate did not differ between the genders. Serum total and low-density lipoprotein cholesterol concentrations decreased by 6% and 8% (p < 0.01 for both), respectively, in both children with the apolipoprotein E 3/4 or 4/4 (apoE4+) phenotype and the apolipoprotein E 2/3 or 3/3 (apoE4-) phenotype. Cholesterol absorption decreased both in the apoE4+ children and in the apoE4- children, but cholesterol synthesis consistently increased in the apoE4+ children only. CONCLUSION: Plant stanol esters reduce serum cholesterol concentration in healthy children irrespective of their gender or apoE4 phenotype.

Apolipoprotein E phenotype regulates cholesterol absorption in healthy 13-month-old children--The STRIP Study.

High serum cholesterol concentration is one of the key risk factors in development of atherosclerosis, which may begin early in life and later progress to symptomatic coronary heart disease. In adults, apoE polymorphism strongly influences cholesterol metabolism, as subjects with apoE 3/4 or 4/4 (collectively called apoE4) phenotype absorb cholesterol effectively and thus also have higher cholesterol absorption-reflecting plant sterol concentrations in serum than subjects with other apoE phenotypes. Because of the inverse correlation of absorption and synthesis of cholesterol, concentrations of cholesterol synthesis-reflecting serum cholesterol precursor sterols are lower in subjects with apoE4 than in subjects with other phenotypes. To analyze whether apoE phenotype affects cholesterol absorption and synthesis in early childhood, we measured serum plant sterol (campesterol and sitosterol) and cholesterol precursor sterol (desmosterol and lathosterol) concentrations in healthy 13-month old children using gas-liquid chromatography. The 36 study children were participants in a randomized prospective trial (the Special Turku Coronary Risk Factor Intervention Project) aimed at decreasing exposure of the children to environmental atherosclerosis risk factors. The 16 apoE4 children had 30% to 50% higher cholesterol-adjusted campesterol and sitosterol concentrations in serum than the 20 apoE 3/3 children (p = 0.002 and p = 0.02, respectively). The concentrations of cholesterol precursor sterols in serum did not differ between the two groups of children. We conclude that the young apoE4 children may absorb cholesterol and plant sterols more effectively than the children with apoE 3/3 phenotype without compensatory reduction in endogenous synthesis of cholesterol.

Dietary plant sterols alter the serum plant sterol concentration but not the cholesterol precursor sterol concentrations in young children (the STRIP Study). Special Turku Coronary Risk Factor Intervention Project.

Plant sterol supplementation reduces serum cholesterol concentration but may increase serum plant sterol concentrations, especially in children. We determined whether natural dietary plant sterols derived mainly from vegetable oil or margarine in early childhood affect serum concentrations of plant sterols (campesterol and sitosterol) and cholesterol precursor sterols (Delta-8 cholestenol, desmosterol, and lathosterol), reflecting endogenous cholesterol synthesis. We measured the serum sterol concentrations using gas liquid chromatography in 20 healthy 13-mo-old intervention children in a randomized, prospective study designed to decrease exposure of the children to known environmental atherosclerosis risk factors and in 20 control children. The diet of the intervention children was rich in plant sterols due to replacement of milk fat with vegetable fat, whereas the diet of the control children contained only small amounts of plant sterols. The intervention children consumed twice as much plant sterols as the control children (P < 0.001). Their serum concentrations of campesterol and sitosterol were 75% and 44% higher, respectively, than those in the control children (P < 0.001 for both), but serum cholesterol precursor sterol concentrations did not differ between the two groups. We conclude that doubling dietary plant sterol intake almost doubles serum plant sterol concentrations in 13-mo-old children, but has no effect on endogenous cholesterol synthesis. Relative intestinal absorption of natural plant sterols from the diet in early childhood is similar to that in adults.

Prospective, randomized, infancy-onset trial of the effects of a low-saturated-fat, low-cholesterol diet on serum lipids and lipoproteins before school age: The Special Turku Coronary Risk Factor Intervention Project (STRIP).

BACKGROUND: We showed previously that repeated dietary counseling during the first 3 years of life reduces the concentration of serum nonfasting cholesterol. We have now extended the study to children 5 years of age and analyzed fasting blood samples, enabling LDL cholesterol calculations for the first time. METHODS AND RESULTS: Families of 7-month-old infants (n=1062) were randomized to a control group (n=522) or an intervention group (n=540) that received individualized dietary counseling with the aims of a fat intake of 30% to 35% of daily energy, a saturated/monounsaturated/polyunsaturated fatty acid ratio of 1:1:1, and a cholesterol intake of <200 mg/d. Nutrient intakes were studied biannually, nonfasting serum lipid values were studied annually, and fasting values were studied at 5 years of age. The intervention children always had lower intakes of saturated fat and cholesterol than the control children. The intervention boys had 0.39 mmol/L (P:<0.0001) lower mean serum cholesterol values than the control boys between 13 and 60 months of age, but among girls, the difference was of marginal significance (0.15 mmol/L, P:=0.052). Five-year-old intervention boys had 9% lower mean serum LDL cholesterol concentrations than the control boys (P:=0.0002; 95% CI, -0.39 to -0.12 mmol/L), whereas no difference was observed in girls. In both sexes, serum triglyceride concentrations were similar in the 2 groups. CONCLUSIONS: The restriction of saturated fat and cholesterol intake by repeated, individualized dietary counseling since infancy resulted in lower serum total and LDL cholesterol concentrations at 5 years of age. However, the effect was significant only in boys.

Neurological development of 5-year-old children receiving a low-saturated fat, low-cholesterol diet since infancy: A randomized controlled trial.

CONTEXT: Early childhood introduction of nutritional habits aimed at atherosclerosis prevention is compatible with normal growth, but its effect on neurological development is unknown. OBJECTIVE: To analyze how parental counseling aimed at keeping children's diets low in saturated fat and cholesterol influences neurodevelopment during the first 5 years of life. DESIGN: Randomized controlled trial conducted between February 1990 and November 1996. SETTING: Outpatient clinic of a university department in Turku, Finland. PARTICIPANTS: A total of 1062 seven-month-old infants and their parents, recruited at well-baby clinics between 1990 and 1992. At age 5 years, 496 children still living in the city of Turku were available to participate in neurodevelopmental testing. INTERVENTION: Participants were randomly assigned to receive individualized counseling aimed at limiting the child's fat intake to 30% to 35% of daily energy, with a saturated:monounsaturated:polyunsaturated fatty acid ratio of 1:1:1 and a cholesterol intake of less than 200 mg/d (n = 540) or usual health education (control group, n = 522). MAIN OUTCOME MEASURES: Nutrient intake, serum lipid concentrations, and neurological development at 5 years, among children in the intervention vs control groups. RESULTS: Absolute and relative intakes of fat, saturated fatty acids, and cholesterol among children in the intervention group were markedly less than the respective values of control children. Mean (SD) percentages of daily energy at age 5 years for the intervention vs control groups were as follows: for total fat, 30.6% (4.5%) vs 33.4% (4.4%) (P<. 001); and for saturated fat, 11.7% (2.3%) vs 14.5% (2.4%) (P<.001). Mean intakes of cholesterol were 164.2 mg (60.1 mg) and 192.5 mg (71. 9 mg) (P<.001) for the intervention and control groups, respectively. Serum cholesterol concentrations were continuously 3% to 5% lower in children in the intervention group than in children in the control group. At age 5 years, mean (SD) serum cholesterol concentration of the intervention group was 4.27 (0.63) mmol/L (165 [24] mg/dL) and of the control group, 4.41 (0.74) mmol/L (170 [29] mg/dL) (P =.04). Neurological development of children in the intervention group was at least as good as that of children in the control group. Relative risks for children in the intervention group to fail tests of speech and language skills, gross motor functioning plus perception, and visual motor skills were 0.95 (90% confidence interval [CI], 0.60-1.49), 0.95 (90% CI, 0.58-1.55), and 0.65 (90% CI, 0.39-1.08), respectively (P =.85,.86, and.16, respectively, vs control children). CONCLUSION: Our data indicate that repeated child-targeted dietary counseling of parents during the first 5 years of a child's life lessens age-associated increases in children's serum cholesterol and is compatible with normal neurological development. JAMA. 2000;284:993-1000

Fatty acid composition of serum cholesterol esters as a reflector of low-saturated-fat, low-cholesterol diet in young children: the STRIP project. The Special Turku coronary Risk factor Intervention 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 14.6 E% 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). In conclusion, CE fatty acid composition did not differ between the intervention and control groups, whereas CE linoleic and total polyunsaturated fatty acids reflected well the differences in their intakes at the individual level.

Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children: the STRIP project. Special Turku Coronary Risk Factors Intervention Project.

OBJECTIVE: To investigate cholesterol-lowering efficacy and safety of plant stanol ester margarine in healthy 6-year-old children already consuming a low-saturated-fat, low-cholesterol diet. STUDY DESIGN: Eighty-one intervention children from the STRIP project, a randomized prospective trial aimed at reducing exposure of young children to the known environmental atherosclerosis risk factors, were recruited to this double-blind crossover study at 6 years of age. In randomized order the families were advised to replace daily 20 g of the child's dietary fat intake with plant stanol ester margarine or control margarine for 3 months. The washout period lasted 6 weeks. Statistical analysis was performed according to intention-to-treat principle with analysis of variance for crossover design. RESULTS: The mean daily plant stanol ester margarine consumption was 18.2 g (1.5 g plant stanol). The well-tolerated plant stanol ester margarine reduced serum total and low-density lipoprotein cholesterol concentrations by 5.4% and 7.5%, respectively (P =.0001 for both). The serum high-density lipoprotein cholesterol and triglyceride concentrations and alpha-tocopherol to low-density lipoprotein cholesterol ratio remained unchanged. The serum beta-carotene to low-density lipoprotein cholesterol ratio decreased by 19% (P =.003). CONCLUSION: Plant stanol ester margarine significantly diminishes serum total and low-density lipoprotein cholesterol concentration without adverse clinical effects in healthy children who already consume a low-saturated-fat, low-cholesterol diet but decreases the serum beta-carotene to low-density lipoprotein cholesterol ratio.

Effect of low-saturated fat, low-cholesterol dietary intervention on fatty acid compositions in serum lipid fractions in 5-year-old children. The STRIP project.

OBJECTIVE: To evaluate the effect of dietary low-saturated fat, low-cholesterol intervention on fat intake and fatty acid compositions in serum cholesterol ester (CE), phospholipid (PL) and triglyceride (TG) fractions in five-year-old children. DESIGN AND SUBJECTS: The STRIP project is a prospective, randomised intervention project in which 1062 seven-month-old infants were recruited from the well-baby clinics. 764 children participated in the 5-year follow-up; 202 of them were randomly selected for this study. Diet was assessed with 4-d dietary records. Serum CE, PL and TG fatty acid compositions were analysed with gas-liquid chromatography. RESULTS: Saturated fat intake of intervention children (mean (confidence interval)) (girls 11.9 (11.2-12.6) % of energy intake (E%); boys 12.5 (11.9-13.1)) was lower than that of the control children (girls 14.4 (13.7-15.2) E%; boys 15.0 (14.3-15. 8) E%) (P=0.0001 for the difference between intervention and control groups). The intake of unsaturated fat differed only slightly. Dietary ratios of polyunsaturated to saturated fatty acids (PS ratios) of the intervention and control diets were 0.44 and 0.33, respectively (P=0.0001). Furthermore, serum cholesterol concentrations of the intervention and control children differed (4. 28 (4.13-4.43) mmol/L vs 4.49 (4.35-4.63) mmol/L; P=0.04). Relative proportion of saturated fatty acids in serum TG was lower (34.9% vs 36.3%; P=0.04) and that of n-6 polyunsaturated fatty acids higher (13.9% vs 12.4%; P=0.0004) in the intervention than in the control children, whereas serum CE and PL fatty acid compositions of intervention and control groups were closely similar. However, intake of linoleic acid correlated better with serum linoleic acid relative content in the CE fraction (r=0.36; P=0.0001) than in the PL (r=0.27; P=0.0002) or in the TG (r=0.23; P=0.0016) fraction. CONCLUSIONS: Intervention resulted in decreased intake of saturated fatty acids and lowered serum total and LDL cholesterol concentrations. Of serum lipid fractions, TG fatty acid composition was the most sensitive and parallelled the findings in dietary food records.

Cardiovascular disease risk factors in young children in the STRIP baby project. Special Turku coronary Risk factor Intervention Project for children.

Introducing nutritional principles of preventive cardiology to the care of young children may improve permanently adherence to a low-saturated-fat, low-cholesterol diet later in life. This approach has not been readily adapted because of worries of the possible effects of such a diet on the growth and development of children. In the STRIP baby project, 1062 infants were randomized at 7 months of age into an intervention group (n = 540) or a control group (n = 522). The counselling of the intervention children aimed at a fat intake of 30% of energy after the age of 1 year and to a 1:1:1 ratio in saturated:monounsaturated:polyunsaturated fat intake. Dietary intake, growth and serum lipid concentrations were monitored in the children regularly through the first years of life. The intake of total fat, saturated fat and cholesterol were lower and the intake of polyunsaturated fat and the ratio of polyunsaturated to saturated fat (P/S) in the diet were higher in the intervention children than in the controls. During the first 3 years of the trial, the serum cholesterol concentration was 3-6% lower in the intervention children than in the controls (95% CI for the mean difference between groups from -0.27 to -0.12 mmol/L). No differences in the growth of the children were observed between the groups. We conclude that repeated individualized counselling aiming at reduced consumption of saturated fat combined with regular follow-up is effective and does not restrict the growth of children.