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Biomedical subjects

Helena Gylling

Publications and source records attributed to Helena Gylling.

15 recordsLinked to original sources
PubMed2003

Squalene and noncholesterol sterols in serum and lipoproteins of children with and without familial hypercholesterolemia.

Squalene and noncholesterol sterols, e.g. lathosterol and plant sterols, the respective markers of cholesterol synthesis and absorption, are transported with cholesterol in serum lipoproteins. Their concentrations and ratios to cholesterol in serum and lipoproteins have not been carefully compared, especially in children and in marked hypercholesterolemia. Thus, we measured these variables with gas-liquid chromatography in 18 children with and 29 without familial hypercholesterolemia, all aged 5-17 y. Concentrations of most noncholesterol sterols were higher in serum, LDL, and intermediate density lipoprotein in the children with than those without familial hypercholesterolemia. Despite accumulation of noncholesterol sterols mainly in LDL (75% in familial hypercholesterolemia and 55% in non-familial hypercholesterolemia, p < 0.001), their ratios were mostly similar in serum and lipoproteins of the two groups. The ratios of squalene and lathosterol were higher in VLDL and intermediate density lipoprotein, whereas in LDL that of lathosterol was lower than the respective serum values in both groups. Absorption marker sterol ratios were highest in HDL in both groups. Thus, even though the ratios of noncholesterol sterols to cholesterol in serum reflect, in general, synthesis and absorption of cholesterol, their ratios in different lipoproteins could give additional information of cholesterol metabolism.

Adolescent↗
PubMed2003

Cholesterol synthesis and absorption in coronary patients with lipid triad and isolated high LDL cholesterol in a 4S subgroup.

We assumed that assaying serum cholesterol precursors (synthesis markers) and plant sterols and cholestanol (absorption markers of cholesterol) reveals differences in cholesterol synthesis and absorption in the Finnish 4S subgroup divided in high triglyceride-low HDL cholesterol (lipid triad=HTG) and isolated high LDL cholesterol (ILDL) groups. Serum squalene and non-cholesterol sterol ratios to cholesterol were measured with gas-liquid chromatography at baseline, 6 weeks, 1 year, and 5 years on simvastatin. Patients with HTG (n=135) exhibited features of metabolic syndrome and, in spite of similar serum total and LDL cholesterol levels, ratios of synthesis markers were higher and those of absorption markers lower than in ILDL (n=133). The latter patients accumulated to a subgroup shown earlier to be clinical non-responders to simvastatin in 4S. Serum cholesterol reduction by simvastatin only tended to be higher in HTG than ILDL. The synthesis marker ratios were markedly reduced, and more effectively in HTG than ILDL, while the absorption marker ratios were increased, and for plant sterols more in ILDL than HTG. In conclusion, HTG is associated with high synthesis and low absorption of cholesterol, these events being opposite in ILDL. Synthesis is more effectively reduced by simvastatin in HTG than ILDL in spite of similar reduction in serum cholesterol. Patients defined by highest baseline absorption marker ratios in ILDL group are poor coronary event-reducers on regular simvastatin treatment.

Absorption↗
PubMed2003

Non-nutritive bioactive constituents of plants: phytosterols.

Normal human diet contains small amounts of phytosterols, mainly sitosterol and campesterol. Intestinal absorption of these plant sterols is low, about one tenth of that of cholesterol, such that their serum concentrations are also low, about 0.1 to 1% of the cholesterol levels. Like cholesterol they are transported by lipoproteins, mainly by LDL, and secreted unchanged in bile. Addition of plant sterols, or especially of their delta-5 saturated derivatives plant stanols into diet as fat-soluble esters inhibit cholesterol absorption and lower serum cholesterol similarly in short-term studies. Long-term consumption of plant stanol esters lowers serum cholesterol to the extent expected to reduce clinical manifestation of coronary heart disease by over 20% without detectable side effects, cholesterol lowering being especially effective in combination with cholesterol synthesis inhibitors statins.

Anticholesteremic Agents↗
PubMed2003

Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins.

We studied changes in serum cholestanol and plant sterols (indexes of cholesterol absorption) and cholesterol precursors (indexes of cholesterol synthesis) in response to cholesterol reduction by way of 1 year's treatment with atorvastatin (n = 102) and simvastatin (n = 105) treatments in patients with coronary heart disease. Serum cholesterol levels and ratios of the precursor sterols to cholesterol after 1 year of treatment were reduced in proportion to the pretreatment values (33% +/- 1% by simvastatin and 36% +/- 1% by atorvastatin; P <.01 for difference between groups) for cholesterol; the respective reductions in the precursor sterol:cholesterol ratios were also higher with atorvastatin (50% +/- 2% for lathosterol) than with simvastatin (42% +/- 1%; P <.01 between groups), but the ratio of squalene to cholesterol was increased (17% +/- 5%, P <.001) by atorvastatin. Plant sterol concentrations were gradually increased by atorvastatin but decreased initially by simvastatin. However, their ratios with respect to cholesterol were increased by as much as 82% with atorvastatin and by as much as 39% with simvastatin. In conclusion, effective inhibition of cholesterol synthesis and subsequent reduction in serum cholesterol levels by statins lead to increases in serum plant-sterol levels, probably as a result of reduced biliary secretion and enhanced absorption of these sterols. Because serum plant sterols have been claimed to be involved in the early development of atherosclerosis, the question arises whether continuously increasing serum plant sterols during long-term statin treatment should be prevented by cholesterol malabsorption (eg, by plant stanol ester consumption), especially in subjects with high baseline plant sterol values and effective sterol absorption.

Anticholesteremic Agents↗
PubMed2003

Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia.

OBJECTIVE: To show whether the ratios of squalene and cholesterol precursor sterols to cholesterol and cholestanol and plant sterols to cholesterol change differently in plasma and especially in the red cells of hypercholesterolemic children during consumption of plant stanol and sterol ester spreads. STUDY DESIGN: In a randomized, double-blind, crossover study, hypercholesterolemic children (n = 23) consumed low-fat plant stanol and sterol ester spreads for 5-week periods separated by a 5-week washout period. Plasma and red cell lipids, squalene, and noncholesterol sterols were measured before and at the end of each period. RESULTS: The plant stanol and sterol ester spreads lowered plasma total (-9% and -6%, respectively) and low-density lipoprotein (-12% and -9%) cholesterol but had no effect on red cell cholesterol, high-density lipoprotein cholesterol, or plasma triglycerides. The ratios of plasma and red cell sitosterol and campesterol to cholesterol decreased by 32% to 36% (P <.001) with the plant stanol ester and increased by 40% to 52% (P <.001) with the sterol ester spread. CONCLUSIONS: Consumption of plant sterols increases and consumption of plant stanols decreases the ratios of plant sterols to cholesterol in red cells of hypercholesterolemic children proportionately to the respective changes in plasma.

Child↗
PubMed2003

Cholesterol precursors and plant sterols in children with food allergy.

BACKGROUND: The data on lipid metabolism in allergic children is limited. OBJECTIVE: We investigated lipid and sterol metabolism in young children whose diets were restricted because of food allergy. DESIGN: Children in group A [n = 21; mean (+/- SD) age: 1.78 +/- 0.73 y] were allergic to fish, eggs, and either cow milk or cereals; those in group B (n = 31, aged 1.45 +/- 0.58 y) were allergic to fish, eggs, and both cow milk and cereals. Cholesterol precursor and plant sterol to cholesterol ratios (10(2) x micro mol/mmol cholesterol) and apolipoprotein E phenotype distributions were analyzed in 36 subjects. The control group for cholesterol precursor and plant sterol measurements consisted of 18 healthy age-matched children. RESULTS: The mean serum cholesterol concentration was 3.6 +/- 0.6 mmol/L, and HDL cholesterol was 1.03 +/- 0.3 mmol/L in group A. Corresponding values in group B were 3.4 +/- 0.7 and 1.09 +/- 0.2 mmol/L. The daily cholesterol intake was low: 61.3 +/- 36.0 mg in group A and 50.7 +/- 48.5 mg in group B. Cholesterol precursor plant sterol concentrations were significantly higher in allergic subjects than in control subjects. CONCLUSIONS: Allergic children with restricted diets have a low intake of cholesterol and relatively low serum cholesterol concentrations. Dietary intake of plant sterols was obviously increased because of supplementation with rapeseed oil, which is rich in plant sterols, leading to elevated plant sterol concentrations. Plant sterols may have inhibited cholesterol absorption, which in turn stimulated cholesterol synthesis in compensation, also explaining the increased precursor sterol ratios in serum in our subjects.

Case-Control Studies↗
PubMed2002

Acute effects of weight reduction on cholesterol metabolism in obese type 2 diabetes.

BACKGROUND: Weight reduction in obese type 2 diabetes increases the absorption efficiency of cholesterol and serum plant sterol levels from baseline. However, there is no information on the effects of acute restriction of calories and lack of dietary cholesterol and plant sterols on serum cholesterol precursor and plant sterols and on cholesterol metabolism. Thus, 10 obese (BMI>30 kg/m(2)) type 2 diabetes subjects consumed very low energy diet virtually free of cholesterol, cholestanol and plant sterols for 3 months. METHODS: Serum sterols were measured with gas-liquid chromatography. RESULTS: Body weight was reduced by 15.5+/-1.7 kg (p<0.001), serum cholesterol by 21+/-3%, triglycerides 45+/-5%, glucose 23+/-3%, insulin 59+/-5% and HbAIc by 8+/-2%, whereas serum sex hormone binding globulin increased by 108+/-25% (p<0.05-0.001 for all). Serum desmosterol and lathosterol to cholesterol ratios (indicators of cholesterol synthesis) were significantly decreased by 20% suggesting that cholesterol synthesis was suppressed. Serum squalene ratio was unchanged. Despite lack of dietary plant sterols and cholestanol, serum campesterol and sitosterol ratios (indicators of cholesterol absorption efficiency) only tended to decrease, whereas serum cholestanol ratio, also an absorption indicator, was increased by 33+/-3% (p<0.001), and its ratios to campesterol and sitosterol were increased by 60% and 31%, suggesting that sterol absorption efficiency might have been increased and their turnover reduced. CONCLUSIONS: In obese type 2 diabetes, restriction of calories and dietary sterols improved markedly control of diabetes, decreased serum cholesterol precursor sterols suggesting that cholesterol synthesis was decreased, but only tended to decrease serum values of plant sterols probably due to their release from the adipose tissues associated with their impaired turnover.

Cholesterol↗
PubMed2002

Ineffective decrease of serum cholesterol by simvastatin in a subgroup of hypercholesterolemic coronary patients.

We measured serum cholesterol concentrations and synthesis markers (e.g. serum lathosterol to cholesterol ratio), and absorption markers (e.g. serum campesterol to cholesterol ratio) of cholesterol in 319 good responders (GR; dose 20 mg up to 1 year) and in 115 poor responders (PR; dose increased at 6 weeks to 40 mg) among Finnish participants in the Scandinavian Simvastatin Survival Study at baseline, 6 weeks and 1 year of the simvastatin treatment. The baseline cholesterol level and the ratios of the absorption markers were higher and those of the synthesis markers lower in PR than GR. The ratios of the precursor sterols were negatively related to the baseline cholesterol in GR only (P=0.003). The cholesterol levels, and the ratios of the precursor sterols were decreased and those of the absorption marker sterols increased less consistently in PR than GR by 20 mg, the group differences being only slightly lessened by the dose addition to 40 mg. One-year differences were still frequently significant. The baseline cholesterol concentrations were negatively related to the reduction of the precursor sterol ratios in GR, the change of cholesterol being positively related to those of the synthesis markers and negatively to those of the absorption markers only in PR. Thus, patients needing large statin dose for cholesterol normalization have high absorption and low synthesis of cholesterol, yet baseline synthesis is inversely related to cholesterol level only in GR. The synthesis rate is less markedly reduced by the large than by the small statin dose in the PR, and the reduction is related, in contrast to that in the GR, to lowering of cholesterol.

Cholestanol↗
PubMed2002

Body weight modulates cholesterol metabolism in non-insulin dependent type 2 diabetics.

OBJECTIVE: Cholesterol metabolism was studied in 64 subjects with type 2 diabetes who had body weight ranging from normal to obese, to find out whether weight interferes with cholesterol metabolism in diabetes. RESEARCH METHODS AND PROCEDURES: Cholesterol absorption was measured with peroral isotopes and by assaying serum plant sterol and cholestanol to cholesterol ratios, cholesterol synthesis with sterol balance, and measuring serum cholesterol precursor ratios. RESULTS: The study population was divided into normal-weight (body mass index, 24.1 +/- 0.4 kg/m2; mean +/- SEM; n = 20) and obese (31.0 +/- 0.5 kg/m2; n = 44) groups. Despite similar serum cholesterol and blood glucose values, fecal neutral sterol excretion, cholesterol and bile acid synthesis, cholesterol turnover (1649 +/- 78 vs. 1077 +/- 52 mg/d; p < 0.001), and serum cholesterol precursors were higher, and cholesterol absorption % (32 +/- 1 vs. 40 +/- 2%; p < 0.05), serum cholestanol, and plant sterols were lower in the obese vs. the non-obese groups. Serum sex hormone-binding globulin was positively associated with variables of cholesterol absorption, whereas blood glucose, serum insulin, and body mass index were associated with variables of cholesterol synthesis. In multiple stepwise regression analysis, cholesterol absorption percentage (R2 = 24%) and body mass index (R2 = 15%) were the only variables explaining the variability of cholesterol synthesis. DISCUSSION: Body weight, through its entire range, regulates cholesterol metabolism in type 2 diabetes such that with increasing insulin resistance, cholesterol absorption is lowered and cholesterol synthesis increased.

Absorption↗
PubMed2002

Cholesterol metabolism in normal and heterozygous familial hypercholesterolemic newborns.

In heterozygous familial hypercholesterolemia (FH), serum low-density lipoprotein (LDL) cholesterol levels are frequently increased in utero. A unique Finnish FH population, FH-North Karelia (FH-NK), has been identified, providing an excellent opportunity to study the diagnostic significance of cholesterol metabolism in FH. For that purpose, we investigated lipoprotein lipids, cholesterol precursors (squalene, methyl, and demethyl sterols), cholestanol, and plant sterols in FH-NK newborns (n = 5), non-FH siblings (n = 7), and controls (n = 20) at birth and after 1-year follow-up in 8 FH-NK and 5 non-FH children. The sum of concentrations (micrograms per deciliter) of methyl sterol (8-monomethylsterol, methostenol, 8-dimethylsterol, 8,24-dimethylsterol, and lanosterol) and squalene was higher in FH newborns than in non-FH siblings but overlapped with one control case. Cord-blood total or LDL cholesterol values could not be used for diagnostic purposes, whereas 1-year LDL cholesterol values were highly superior to those measured at birth. The methyl sterol ratio in cord blood was 29 to 193 10(2) mmol/mol cholesterol and was undetectable in serum at the age of 1 year; those of the demethyl precursor sterols were 1.5 to 8 times higher in cord blood than in serum at the age of 1 year, suggesting that cholesterol synthesis was markedly increased at birth. Plant sterols, not synthesized in human beings, were already present in serum of all the groups at birth, indicating their transfer, apparently with cholesterol, from mother to fetus. Babies born to FH mothers showed a greater tendency toward accelerated cholesterol synthesis than did those born to FH fathers. Despite signs of markedly high but similar synthesis of cholesterol at birth in FH and non-FH newborns, the diagnosis of FH was questionable by measurement of cholesterol precursors or LDL cholesterol in cord blood. The latter measurement, at the 1-year mark, is superior for diagnostic purposes.

Cholesterol↗
PubMed2002

Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion.

Properties of the intestinal digestion of the dietary phytosterols, cholesterol and cholestanol, and the mechanisms by which phytosterols inhibit the intestinal absorption of cholesterol in healthy human subjects are poorly known. We have studied the hydrolysis of dietary plant sterol and stanol esters and their subsequent micellar solubilization by determining their concentrations in micellar and oil phases of the jejunal contents. Two liquid formulas with low (formula 1) and high (formula 2) plant stanol concentrations were infused via a nasogastric tube to the descending duodenum of 8 healthy human subjects, and intestinal contents were sampled for gas-liquid chromatographic sterol analysis 60 cm more distally. During the duodenal transit, phytosterol esters were hydrolyzed. This was especially profound for sitostanol, as its esterified fraction per milligram of sitosterol decreased 80% (P < 0.001) in formula 1 and 61% (P < 0.001) in formula 2. Contrary to that, esterified fraction of cholesterol per milligram of sitosterol was increased fourfold (P < 0.001) in formula 1 and almost sixfold (P < 0.001) in formula 2, whereas that of cholestanol remained unchanged. Percentages of esterified sterols and stanols in total intestinal fluid samples were higher after the administration of formula 2 than of formula 1. Esterified cholesterol and stanols accumulated in the oil phase, and free stanols replaced cholesterol in the micellar phase. At high intestinal plant stanol concentrations, cholesterol looses its micellar solubility possibly by replacement of its free fraction in the micellar phase by hydrolyzed plant stanols, which leads to a decreased intestinal absorption of cholesterol.

Cholesterol↗
PubMed2002

Inheritance of cholesterol metabolism of probands with high or low cholesterol absorption.

Heredity of cholesterol absorption and synthesis was studied in siblings of hypercholesterolemic probands with low and high serum cholestanol to cholesterol ratio (assumed to indicate low and high absorption of cholesterol, respectively). Cholesterol synthesis was assayed with sterol balance technique and measuring serum cholesterol precursor to cholesterol ratios (synthesis markers of cholesterol), and cholesterol absorption with measuring dietary cholesterol absorption percentage and serum plant sterol and cholestanol to cholesterol ratios (absorption markers of cholesterol). In the siblings of the low absorption families, cholesterol absorption percentage and ratios of absorption markers were significantly lower, and cholesterol and bile acid synthesis, cholesterol turnover, fecal steroids and ratios of synthesis markers significantly higher than in the siblings of the high absorption families. The ratios of absorption and synthesis markers were inversely interrelated, and they were correlated with cholesterol absorption and synthesis in the siblings. In addition, low absorption was associated with high body mass index, low HDL cholesterol, and serum sex hormone binding globulin levels, suggesting that low absorption was associated with metabolic syndrome. Intrafamily correlations were significant for serum synthesis markers, cholestanol, triglycerides, and blood glucose level. In conclusion, cholesterol absorption efficiency and synthesis are partly inherited phenomena, and they can be predicted by the ratios of non-cholesterol sterols to cholesterol in serum.

Absorption↗
PubMed2002

Combination therapy with statins.

Statins effectively inhibit cholesterol synthesis and are currently the most commonly used drugs for the treatment of hypercholesterolemia. However, patients with familial hypercholesterolemia and those unwilling to take, or who cannot tolerate statins, and patients with combined hyperlipidemia require a combination treatment. Statins combined with cholesterol malabsorption, caused, e.g., by plant stanol esters or ezetimibe (Schering-Plough Corp/Merck & Co Inc), or with bile acid malabsorption, caused by bile acid binding resins or guar gum, inhibit compensatory increases in cholesterol synthesis and effectively lower LDL cholesterol levels. Combination therapy of statins with fibrates should be controlled by lipidology experts. Recent information on indications and advantages of combining statins with n-3 fatty acids, hormone replacement therapy, or niacin, will also be discussed.

Animals↗
PubMed2001

A review of clinical trials in dietary interventions to decrease the incidence of coronary artery disease.

Of the associations between dietary elements and coronary artery disease (CAD), the greatest body of evidence deals with the beneficial effect of reducing the dietary intake of saturated fatty acids and cholesterol. Furthermore, it is well established, on the basis of convincing evidence, that reduction in serum total cholesterol results in reduction in coronary morbidity and mortality, as well as in regression of other atherosclerotic manifestations.In fact, dietary intervention studies revealed that it is possible to reduce the incidence of coronary death and nonfatal myocardial infarction, as well as manifestations of atherosclerosis in cerebral and peripheral arteries, by reducing dietary intake of saturated fat and cholesterol. In two recently reported dietary interventions the incidence of coronary events, especially coronary mortality, and total mortality were reduced by increased intake of n-3 long-chain polyunsaturated fatty acids and by a modification of the diet toward a Mediterranean-type diet (rich in alpha-linolenic acid. In addition to those findings, the potential efficacy of the dietary newcomers phytostanol and phytosterol esters on reducing coronary incidence is discussed in the present review.

Journal Article↗