![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
2
*
The Research Centre of Applied and Preventive Cardiovascular Medicine and the Departments of
Pediatrics and
**
Medicine, University of Turku, Turku, Finland; the
Department of Medicine, University of Helsinki, Helsinki, Finland, the
National Public Health Institute, Helsinki, Finland; and the
Research and Development Centre of the Social Insurance Institution, Turku, Finland
2To whom correspondence should be addressed. E-mail: anne.tammi{at}utu.fi
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
-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.
KEY WORDS: • plant sterols • campesterol • sitosterol • cholesterol precursor sterols • children
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
200–300 mg of plant
sterols to adults, so that amounts consumed each day are similar to
those of cholesterol (1
,2)
. The main dietary sources of
plant sterols are vegetable oils, seeds, nuts and cereals
(3)
. Consequently, vegetarians consume more of these
sterols than do subjects who consume a conventional Western diet
(4
,5)
. In general, only 5–10% of the ingested major
plant sterols, sitosterol, campesterol and stigmasterol is absorbed
(6)
, while cholesterol absorption may exceed 50%. Because
no plant sterols are synthesized in humans, all plasma and tissue plant
sterols are entirely of dietary origin. Serum plant sterol
concentrations reflect cholesterol absorption (1
,7)
, but
are also affected by dietary plant sterol intake (8)
.
Serum plant sterol concentration is extremely high in patients with
sitosterolemia, a rare familial lipid storage disease with accelerated
atherosclerosis (9)
. Because hypercholesterolemic patients
with premature coronary heart disease may also have moderately high
serum plant sterol concentrations (10)
, high serum plant
sterol concentrations have been associated with risk of premature
atherosclerosis (10
,11)
.
Dietary recommendations (12
,13)
aiming at
atherosclerosis prevention in childhood suggest replacement of SFA in
the diet with MUFA- and PUFA. Such modification of the diet leads to
increased intake of vegetable oil and, consequently, to increased
intake of plant sterols. Surprisingly, high serum plant sterol
concentrations have previously been reported in infants and children
consuming vegetable oil-enriched diets (14)
, but not
in adults who consume such a fat-modified diet. Therefore, we
studied whether daily supplementation of 7–17 g vegetable oil or
margarine containing natural plant sterols elevates serum plant sterol
concentrations in healthy 13-mo-old children. We measured serum plant
sterols in 20 children, who for several months had consumed vegetable
fat-supplemented diets and had high intakes of plant sterols, and
in 20 children, who consumed conventional diets with low plant sterol
content. In addition, to determine whether increased intake of plant
sterols affects endogenous cholesterol synthesis, we assessed
cholesterol precursor sterol concentrations in the same children.
|
SUBJECTS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
The children were all 13-mo-old participants of the Special Turku
Coronary Risk Factor Intervention Project for children (STRIP project),
which is a randomized, prospective trial designed to decrease exposure
of the intervention children to known environmental atherosclerosis
risk factors. In the project, launched in 1990, 1062 infants were
randomly assigned to the intervention (n = 540) or
control (n = 522) group at the age of 7 mo as
described (15)
. The intervention families visited the
study pediatrician and dietitian at the child’s age of 7, 8, 10 and 13
mo. The intervention families were advised to supply the child with a
diet low in saturated fat and cholesterol; these diets included, e.g.,
changes from breast milk or formula to skim milk at 1 y of age and
supplementation of the child’s daily diet with 2–3 teaspoonfuls
(10–15 g) of vegetable oil or margarine, preferably low erucic acid
rapeseed oil. The goal for each child’s total fat intake was 30–35%
of daily total energy. The counseling dealt mainly with quality of fat,
replacement of SFA with PUFA and MUFA to approach a
polyunsaturated/monounsaturated/saturated fatty acid ratio of 1/1/1 and
daily cholesterol intake < 200 mg. Control families visited the
project pediatrician and dietitian at child’s ages of 7 and 13 mo.
They were counseled like families in the Finnish well-baby clinics
to change the child from breast milk or formula to cow’s milk with
1.9% or 2.9% fat at the age of one year and, thus, the child received
no supplementation with vegetable oil. The control families received no
individualized dietary advice. The intervention and control families
recorded each child’s food consumption using a food diary for 3
consecutive d/wk before each visit. The intake data were calculated
using Micro-Nutrica program (Research and Development Unit, Social
Insurance Institution, Turku, Finland) (16)
. Daily intake
of plant sterols was estimated using a database developed at the
National Public Health Institute in mid-1990s. Sterol values of foods
analyzed chemically ranged from 70% to 98% of the calculated sterol
values (17)
. The study was approved by the Joint
Commission on Ethics of the Turku University and the Turku University
Central Hospital. Informed consent was obtained from the parents of all
children.
To study the effect of dietary plant sterols on serum concentrations of
plant sterols, we compared serum sterol concentrations in 20
intervention children (diet rich in plant sterols) and 20 children from
the control group (diet low in plant sterols) from the STRIP project
(Table 1
). Because subjects with
apoE3
3/4 or E 4/4 phenotype absorb cholesterol more effectively
(18)
and have higher serum plant sterol concentration than
subjects with the most common apoE 3/3 (19)
, we only
included children with apoE 3/3 phenotype in this study.
|
Venous blood samples were drawn from nonfasting, 13-mo-old children.
Serum was stored at -70°C. Serum concentrations of cholesterol,
plant sterols and cholesterol precursor sterols [-8 cholestenol,
desmosterol and lathosterol, i.e., sterols immediately preceding
cholesterol in its endogenous synthesis pathway, known to reflect
cholesterol synthesis rate (1
,20)
] were measured by gas
liquid chromatography (21
,22)
using a 50-m capillary SE-30
column (Hewlett-Packard Ultra I, Palo Alto, CA). ApoE phenotypes were
determined using isoelectric focusing and immunoblotting of delipidated
serum (23)
.
Statistical analyses.
The results were expressed as means ± SD. For statistical analysis, the SAS, Version 6.12 program package was used (SAS Institute, Cary, NC). Differences between the intervention children and the control children were tested using two-sample t test, and Pearson correlation coefficients were calculated for correlations between variables. Two-sided P values < 0.05 were considered significant.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
. The high plant sterol diet
also contained more MUFA and PUFA and less SFA than did the control
diet, and, consequently, the PUFA to SFA ratio of the
intervention diet was higher than that of the control diet. However,
the intakes of total fat and energy did not differ between the groups
(Table 1)
.
Serum campesterol and sitosterol concentrations were 75% and 44%
higher in the intervention children than in the control children,
respectively (Table 2
). To eliminate the effect of differing cholesterol concentrations in
the intervention and control children, we also calculated the ratios of
serum concentrations of the noncholesterol sterols to cholesterol.
These cholesterol-adjusted serum campesterol and sitosterol
concentrations in the intervention children were 84% and 51% higher,
respectively, than those in the control children (Table 2)
. The
unadjusted and serum cholesterol-adjusted -8-cholestenol,
desmosterol and lathosterol did not differ between the two groups,
except that unadjusted serum desmosterol concentration was slightly
higher (16%) in the control children than in the intervention children
(Table 2)
.
|
). The dietary sitosterol and campesterol intakes correlated separately
with their own serum concentrations. Dietary intake of plant sterols
correlated inversely with serum concentration of desmosterol. Dietary
intake of PUFA correlated positively with serum campesterol and
sitosterol concentrations, but inversely with desmosterol
concentration. Conversely, daily dietary intake of SFA correlated
inversely with serum sitosterol and campesterol concentration, but
positively with serum desmosterol concentration.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Replacement of milk fat, which is rich in SFA, but contains no plant
sterols with low erucic acid rapeseed oil, which is rich in MUFA and
plant sterols, from the age of 12 mo onward led not only to greater
intake of PUFA and MUFA, but also to a 100% greater intake of plant
sterols compared with children consuming conventional Finnish baby
diet. The mean relative daily plant sterol intake of 139 mg/1000 kcal
(4.19 MJ) by the intervention children exceeds the daily intake values
of adults eating conventional Western diet [80–120 mg/1000 kcal (4.19
MJ)] (1
,2)
. The increase in plant sterol intake was
reflected in serum plant sterol concentrations. The simple replacement
of milk fat with rapeseed oil increased the serum concentrations of
sitosterol and campesterol and led to values that were higher than
those measured in the control children. The difference in serum
sitosterol concentration in the two groups of 13-mo-old children
consuming the two different diets was in accordance with adult data,
suggesting that a 1.5-fold increase in intake led to a 40%
increase in serum sitosterol concentration (8)
. In
contrast, a 8-fold increase in sitosterol intake led to only a 100%
increase in plasma sitosterol concentration (6)
. Enhanced
elimination of plant sterols may limit their rise in serum because the
biliary clearance rate of plant sterols is higher in vegetarians
consuming food rich in plant sterols than in subjects with low dietary
plant sterol intake (5)
. Our data strongly suggest that
during a low to moderate dietary intake, plant sterol absorption in
healthy 13-mo-old children occurs at a rate similar to that of adults.
Meanwhile, plant sterol concentrations increase substantially if
infants and children consume very high amounts of vegetable oil
[376–622 mg/1000 kcal (4.19 MJ) of plant sterols] (14)
because the concentrations may increase 3- to 5-fold to mean
concentrations of campesterol and sitosterol of 95.4 µmol/L and 111.0
µmol/L, respectively. However, in that study (14)
, some
study children had hypercholesterolemia, possibly at least partly due
to increased intestinal absorption of cholesterol and plant sterols
(1
,7)
. It is not known whether a very high intake of plant
sterols by healthy children (e.g., when children use plant
sterol-enriched vegetable margarine) markedly increases serum plant
sterol levels compared with those observed in our study.
High serum plant sterol concentrations are associated with increased
coronary heart disease risk in adults (10
,11)
. In
sitosterolemia, a rare familial lipid storage disease leading to
accelerated atherosclerosis, serum concentrations of sitosterol and
campesterol are extremely high, reaching values up to 1500 µmol/L and
640 µmol/L, respectively, due to enhanced absorption of the plant
sterols (9)
. In case studies, very high serum
concentrations of sitosterol (320 µmol/L) and campesterol (160
µmol/L) have been measured in occasional patients presenting with
xanthomatosis and arthritis (24)
. However, the Western
diet, even if enriched with vegetable oil, usually provides plant
sterols only in amounts not exceeding 400 mg/d (8)
. Even
exceptionally high intake of plant sterols (950 mg/d, containing added
sitosterol) by adults have led to only moderately high serum sitosterol
and campesterol concentrations (8.9 µmol/L and 10.2 µmol/L,
respectively) (8)
. However, when daily plant sterol intake
was up to 2–3 g due to use of plant sterol ester-enriched
vegetable margarine, serum plant sterol concentrations increased
substantially (25
,26)
, suggesting that the increase in
serum plant sterol concentration during consumption of plant sterols is
somewhat dependent on the dose ingested. In nonsitosterolemic subjects,
the high serum cholesterol concentration obviously is the key factor
that results in accelerated coronary heart disease, not the high serum
plant sterol concentration. High serum cholesterol concentration is
usually accompanied by high serum plant sterol concentration, which
reflects not only dietary intake of plant sterols, but also enhanced
cholesterol absorption (1
,7)
.
Because synthesis and absorption of cholesterol are inversely
correlated (27)
, serum concentrations of cholesterol
precursor sterols reflecting endogenous cholesterol synthesis
(1
,20)
and plant sterols reflecting intestinal cholesterol
absorption (1
,7)
correlate inversely with each other in
cross-sectional population studies (28)
. In
nonintervention studies of adults, dietary plant sterols decrease
intestinal cholesterol absorption and lead to a compensatory increase
in cholesterol synthesis (27)
. In our study, the
cholesterol-adjusted concentrations in the intervention children
and control children of all three measured precursor sterols,
-8-cholestenol, desmosterol and lathosterol were similar. This
suggests that the possible decrease in cholesterol absorption induced
by the high plant sterol intake was too small to induce compensatory
activation of endogenous cholesterol synthesis. In addition, children
with high plant sterol intake had much smaller intakes of saturated
fatty acids compared with the children with low plant sterol intake.
Saturated fatty acids suppress hepatic low density lipoprotein receptor
activity, resulting in increased cholesterol synthesis
(29)
. Consistent with this, daily dietary intake of
saturated fatty acids correlated positively with the markers of
cholesterol synthesis in the present study. Thus, low intake of
saturated fatty acids in the children with high plant sterol intake may
result in higher low density lipoprotein receptor activity and,
consequently, to low cholesterol synthesis in the liver and low
cholesterol precursor sterol concentrations in serum.
In summary, vegetable fat supplementation resulting in doubling of
dietary plant sterol intake leads to 60% greater serum plant sterol
concentrations in healthy 13-mo-old children, suggesting that
absorption of plant sterols by healthy young children occurs with
closely similar efficiency than in adults.
|
FOOTNOTES |
|---|
3 Abbreviations used: apoE, apolipoprotein E.
Manuscript received January 2, 2001. Revision accepted April 19, 2001.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
1.
Miettinen T. A., Tilvis R. S., Kesäniemi Y. A. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am. J. Epidemiol. 1990;131:20-31
2. Morton G. M., Lee S. M., Buss D. H., Lawrance P. Intakes and major dietary sources of cholesterol and phytosterols in the British diet. J. Hum. Nutr. Diet 1995;8:429-440
3. Weihrauch J., L & Gardner J. L. Sterol content of foods of plant origin. J. Am. Diet. Assoc. 1978;73:39-47[Medline]
4.
Cerqueira M. T., McMurry Fry M., Connor W. E. The food and nutrient intakes of the Tarahumara Indians of Mexico. Am. J. Clin. Nutr. 1979;32:905-915
5.
Vuoristo M., Miettinen T. A. Absorption, metabolism, and serum concentrations of cholesterol in vegetarians: effects of cholesterol feeding. Am. J. Clin. Nutr. 1994;59:1325-1331
6. Salen G., Ahrens E. H., Jr, Grundy S. M. Metabolism of ß-sitosterol in man. J. Clin. Invest. 1970;49:952-967
7.
Tilvis R. S., Miettinen T. A. Serum plant sterols and their relation to cholesterol absorption. Am. J. Clin. Nutr. 1986;43:92-97
8. Vanhanen H. T., Miettinen T. A. Effects of unsaturated and saturated dietary plant sterols on their serum contents. Clin. Chim. Acta 1992;205:97-107[Medline]
9. Salen G., Shefer S., Nguyen L., Ness G. C., Tint G. S., Shore V. Sitosterolemia. J. Lipid Res. 1992;33:945-955[Abstract]
10. Glueck C. J., Speirs J., Tracy T., Streicher P., Illig E., Vandegrift J. Relationships of serum plant sterols (phytosterols) and cholesterol in 594 hypercholesterolemic subjects and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives. Metabolism 1991;40:842-848[Medline]
11.
Nguyen T. T. The cholesterol-lowering action of plant stanol esters. J. Nutr. 1999;129:2109-2112
12.
National Cholesterol Education Program Expert Panel on Blood Cholesterol Levels in Children and Adolescents National Cholesterol Education Program (NCEP): highlights of the report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 1992;89:495-501
13. The European Society of Pediatric Gastroenterology and Nutrition. Committee on Nutrition Committee report: childhood diet and prevention of coronary heart disease. J. Pediatr. Gastroenter. Nutr. 1994;19:261-269[Medline]
14.
Mellies M. J., Glueck C. J., Sweeney C., Fallat R. W., Tsang R. C., Ishikawa T. T. Plasma and dietary phytosterols in children. Pediatrics 1976;57:60-67
15. Lapinleimu H., Viikari J., Jokinen E., Salo P., Routi T., Leino A., Rönnemaa T., Seppänen R., Välimäki I., Simell O. Prospective randomized trial in 1062 infants of diet low in saturated fat and cholesterol. Lancet 1995;345:471-476[Medline]
16. Hakala P., Marniemi J., Knuts L.-R., Kumpulainen J., Tahvonen R., Plaami S. Calculated vs analysed nutrient composition of weight reduction diets. Food Chem 1996;57:71-75
17. Heinonen M., Valsta L., Anttolainen M., Ovaskainen M.-L., Hyvönen L., Mutanen M. Comparisons between analyzed and calculated food composition data: carotenoids, retinoids, tocopherols, tocotrienols, fat, fatty acids and sterols. J. Food Comp. Anal. 1997;10:3-13
18. Kesäniemi Y. A., Ehnholm C., Miettinen T. A. Intestinal cholesterol absorption efficiency in man is related to apoprotein E phenotype. J. Clin. Invest. 1987;80:578-581
19. Uusitupa M. I., Miettinen T. A., Sarkkinen E. S., Ruuskanen E., Kervinen K., Kesäniemi Y. A. Lathosterol and other non-cholesterol sterols during treatment of hypercholesterolemia with beta-glucan rich oat bran. Eur. J. Clin. Nutr. 1997;51:607-611[Medline]
20. Kempen H.J.M., Glatz J.F.C., Gevers Leuven J. A., van der Voort H. A., Katan M. B. Serum lathosterol is an indicator of whole-body cholesterol synthesis in humans. J. Lipid Res. 1988;29:1149-1156[Abstract]
21. Miettinen T. A., Koivisto P. Non-cholesterol sterols and bile acid production in hypercholesterolaemic patients with ileal bypass. Paumgartner G. Stiehl A. Gerok W. eds. Bile Acids and Cholesterol in Health and Disease 1983:183-187 MTP Press Lancaster, England.
22. Miettinen T. A. Cholesterol metabolism during ketokonazole treatment in man. J. Lipid Res. 1988;29:43-51[Abstract]
23. Lehtimäki T., Moilanen T., Viikari J., Åkerblom H. K., Ehnholm C., Rönnemaa T., Marniemi J., Dahlen G., Nikkari T. Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study. J. Lipid Res. 1990;31:487-495[Abstract]
24. Shulman R. S., Bhattacharyya A. K., Connor W. E., Fredrickson D. S. ß-sitosterolemia and xanthomatosis. N. Engl. J. Med. 1976;294:482-483[Medline]
25. Westrate J. A., Meijer G. W. Plant sterol-enriched margarines and reduction of plasma total and LDL-cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur. J. Clin. Nutr. 1998;52:334-343[Medline]
26.
Jones P. J., Raeini-Sarjaz M., Ntanios F., Vanstone C. A., Feng J. Y., Parsons W. E. Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. J. Lipid Res. 2000;41:697-705
27. Grundy S. M., Ahrens E. H., Jr, Davignon J. The interaction of cholesterol absorption and cholesterol synthesis in man. J. Lipid Res. 1969;10:304-315[Abstract]
28. Sutherland W.H.F., Robertson M. C., Williamson S. A., Nye E. R. Plasma noncholesterol sterols in male distance runners and sedentary men. Eur. J. Appl. Physiol. 1991;63:119-123
29.
Dietschy J. M. Theoretical considerations of what regulates low-density-lipoprotein and high-density-lipoprotein cholesterol. Am. J. Clin. Nutr. 1997;65:S1581-S1589
This article has been cited by other articles:
|
|
 |
|
  P. O. Kwiterovich Jr., S. C. Chen, D. G. Virgil, A. Schweitzer, D. R. Arnold, and L. E. Kratz Response of obligate heterozygotes for phytosterolemia to a low-fat diet and to a plant sterol ester dietary challenge J. Lipid Res., June 1, 2003; 44(6): 1143 - 1155. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
