scholarly journals Validity of animal models for the cholesterol-raising effects of coffee diterpenes in human subjects

1999 ◽  
Vol 58 (3) ◽  
pp. 551-557 ◽  
Author(s):  
Baukje de Roos ◽  
Janet K. Sawyer ◽  
Martijn B. Katan ◽  
Lawrence L. Rudel

Cafestol and kahweol, coffee lipids present in unfiltered coffee brews, potently increase LDL-cholesterol concentration in human subjects. We searched for an animal species in which cafestol similarly increases LDL-cholesterol. Such an animal model could be used subsequently as a model to study the mechanism of action of cafestol and kahweol. Cafestol and kahweol increased serum lipids in African green monkeys (Cercopithecus aethiops), cebus (Cebus apella) and rhesus (Macaca mulatta) monkeys, hamsters, rats and gerbils differently from the increase in human subjects. In African green monkeys, the rise in total cholesterol was less pronounced than that in human subjects. In addition, the increase in total cholesterol was predominantly due to a rise in HDL-cholesterol rather than LDL-cholesterol. Thus, the rise in plasma lipids might illustrate the mechanism in these monkeys rather than the mechanism in human subjects. In other animal species, cafestol and kahweol did not raise cholesterol consistently. The variability in effects on serum lipids could not be explained by the mode of administration or dose of diterpenes, nor by the amount of cholesterol in the diet. In conclusion, we did not find an animal model in which cafestol and kahweol elevate plasma lipoproteins to the same extent as in human subjects. For the time being, therefore, studies on the mechanism of action should be done preferably in human subjects.

2001 ◽  
Vol 86 (2) ◽  
pp. 233-239 ◽  
Author(s):  
Robert Volpe ◽  
Leena Niittynen ◽  
Riitta Korpela ◽  
Cesare Sirtori ◽  
Antonello Bucci ◽  
...  

The objective of the present study was to assess the effect of consumption of a yoghurt-based drink enriched with 1–2 g plant sterols/d on serum lipids, transaminases, vitamins and hormone status in patients with primary moderate hypercholesterolaemia. Thirty patients were randomly assigned to one of two treatment groups: a low-fat low-lactose yoghurt-based drink enriched with 1 g plant sterol extracted from soyabean/dv.a low-fat low-lactose yoghurt, for a period of 4 weeks. After a 2-week wash-out period, patients were crossed over for an additional 4-week period. Second, after a 4-week wash-out period, eleven patients were treated with 2 g plant sterols/d in a second open part of the study for a period of 8 weeks. The yoghurt enriched with plant sterols significantly reduced, in a dose-dependent manner, serum total cholesterol and LDL-cholesterol levels and LDL-cholesterol:HDL-cholesterol (P<0·001), whereas no changes were observed in HDL-cholesterol and triacylglycerol levels, either in the first or the second part of the study. There were only slight, not statistically significant, differences in serum transaminase, vitamin and hormone levels. To conclude, a low-fat yoghurt-based drink moderately enriched with plant sterols may lower total cholesterol and LDL-cholesterol effectively in patients with primary moderate hypercholesterolaemia.


1972 ◽  
Vol 27 (2) ◽  
pp. 395-405 ◽  
Author(s):  
J. I. Mann ◽  
A. S. Truswell

1. Fasting serum cholesterol and triglyceride, and post prandial insulin secretion and lipaemia were measured in human subjects in a metabolic ward, who were given an ordinary diet (diet 1) in which the sucrose was isocalorically replaced by starch (diet 2) or vice versa. The subjects were nine healthy normolipaemic adult males. In eight of these subjects the effect of sucrose calorie reduction (diet 3) on fasting serum lipids was also studied.2. When starch replaced sucrose, there were no singnificant differences in fasting serum lipid concentrations or immunoreactive insulin or in the insulin response and alimentary lipaemia after a standard mixed breakfast.3. Serum triglyceride concentration fell and cholesterol concentration rose during the period of sucrose (and calorie) restriction.4. After lunch and supper on the first two diets (when different carbohydrates were given) the lipaemic response was larger and the insulin response smaller after meals containing sucrose.5. Thus, there was no difference between concentrations of fasting serum lipids when starch replaced sucrose at 23% total calories, but the concentrations of serum triglycerides were higher after individual mixed meals containing sucrose.6. There were no significant differences in the fatty acid patterns of serum lipids on the different diets.


PEDIATRICS ◽  
1994 ◽  
Vol 94 (4) ◽  
pp. 489-493 ◽  
Author(s):  
Terho Lehtimäki ◽  
Tapio Nikkari ◽  
Kimmo Porkka ◽  
Jorma Viikari ◽  
Christian Ehnholm ◽  
...  

Background. Apolipoprotein E (apoE) phenotype is a genetic determinant of plasma total cholesterol and low density lipoprotein (LDL) cholesterol concentrations, that are classical coronary heart disease risk factors. ApoE appears in three major isoforms E2, E3, and E4, coded by corresponding alleles ∈2, ∈3, and ∈4. These give rise to six different phenotypes. Objective. To study the associations of apoE phenotype with cord serum lipids (during minimal enteral nutrition), and with serum lipids of 3-year-old children. Subjects and methods. We determined serum lipid levels and apoE phenotypes in 206 newborns and 259 3-year-old children in connection with a larger follow-up study of atherosclerosis precursors in children and young adults. ApoE phenotyping was done directly from plasma by isoelectric focusing followed by immunoblotting. Results. The effect of apoE phenotype on serum total and LDL cholesterol was significantly different in newborns and 3-year-old children (two-way ANOVA, interaction between apoE phenotype and age group: P &lt; .001 for both). In 3-year-old children, the concentrations of serum total cholesterol and LDL cholesterol increased with apoE phenotype in the order of E3/2, E3/3, E4/3, and E4/4, in both males and females (P &lt; .0001). On the contrary, in neonates total cholesterol and LDL cholesterol concentrations were low and did not differ significantly between apoE phenotypes (P &gt; .05) either in males or in females. The mean serum levels of triglycerides and high density lipoprotein cholesterol did not differ between apoE phenotypes either in 3-year-old children or newborns. Conclusions. The results show that the differences in serum total and LDL cholesterol levels between apoE phenotypes are formed after birth by the influence of environmental factors and suggest that both genetic and external factors influence the levels of serum cholesterol concentrations during the first years of life.


1999 ◽  
Vol 45 (8) ◽  
pp. 1214-1223 ◽  
Author(s):  
Philip J Garry ◽  
Richard N Baumgartner ◽  
Steven G Brodie ◽  
George D Montoya ◽  
Hwa Chi Liang ◽  
...  

Abstract Background: Pharmacogenomics, the study of genetic loci that modulate drug responsiveness, may help to explain why estrogen replacement therapy (ERT) has differential effects on serum lipid and lipoprotein concentrations in postmenopausal women who inherit distinct alleles of the apolipoprotein E gene (APOE). Methods: We compared total-cholesterol, triglyceride, and lipoprotein (LDL and HDL) concentrations in 66 postmenopausal women receiving ERT ([+]ERT) with 174 postmenopausal women not receiving ERT ([−]ERT), controlling for three APOE genotypes divided into three groups: E2 (ε2/ε3, n = 31), E3 (ε3/ε3, n = 160), and E4 (ε3/ε4 + ε4/ε4, n = 49). Results: Mean total-cholesterol concentrations were lower in all three [+]ERT groups compared with their [−]ERT counterparts but were statistically significant only for women in group E4 (P = 0.014). The mean LDL-cholesterol concentrations were significantly lower in all three [+]ERT groups compared with their [−]ERT counterparts (P ≤0.005). Although all three groups of [+]ERT women tended to have higher mean HDL-cholesterol concentrations compared with their [−]ERT counterparts, the differences were not statistically significant. [+]ERT women in groups E2 and E3 had significantly higher (P &lt;0.05) triglyceride concentrations than their [−]ERT counterparts. In [+]ERT women, the ratios of total and LDL-cholesterol to HDL-cholesterol were significantly higher in group E3 and E4 women compared with E2 women (P &lt;0.006). Group E4 [+]ERT women had ratios of total and LDL-cholesterol to HDL-cholesterol that were comparable to group E2 [−]ERT women. Conclusions: Triglyceride concentrations in group E2 [+]ERT women may need to be monitored more closely than those in E3 or E4 [+]ERT women. Group E4 women should probably be targeted for ERT. Results suggest that APOE genotypes have a differential effect on serum lipids and lipoproteins in [+]ERT postmenopausal women.


2010 ◽  
Vol 103 (04) ◽  
pp. 780-787 ◽  
Author(s):  
Eduardo Esteve ◽  
Antoni Castro ◽  
Jose Maria Moreno ◽  
Joan Vendrell ◽  
Wifredo Ricart ◽  
...  

SummaryBactericidal/permeability-increasing protein (BPI), a major constituent of neutrophils that possesses anti-inflammatory properties, shows a structure similar to some proteins implicated in lipid metabolism. We evaluated circulating BPI as a biomarker of endothelial function and lipid metabolism. Circulating BPI concentrations (ELISA) and serum lipids were measured in 202 Caucasian non-smoking men. In a subgroup of 91 consecutive subjects brachial vascular reactivity (high resolution external ultrasound) was assessed. Plasma BPI concentrations were positively associated with total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) (r= 0.203, 0.204 and 0.18; all p<0.05, respectively). In a multiple linear regression analysis, BPI levels were independent contributors to the variance of HDL-C, total cholesterol and LDL-cholesterol after adjusting for age, body mass index and glucose tolerance status. Plasma BPI concentration correlated positively with endothelium-dependent vasodilatation (r=0.277; p<0.05) and HDL-C (r=0.36; p<0.05) in subjects with normal glucose tolerance. In conclusion, circulating BPI could constitute a biomarker of lipid metabolism in subjects with normal glucose tolerance and could help to identify those subjects with preserved endothelial function.


2003 ◽  
Vol 22 (3) ◽  
pp. 213-219
Author(s):  
Lidija Memon ◽  
Vesna Spasojevic-Kalimanovska ◽  
Pavle Jovic ◽  
Slavica Spasic ◽  
Natasa Bogavac-Stanojevic

Quantification of cholesterol in biological membranes is an important step toward understanding of metabolism of intracellular cholesterol, composition of cell membrane and plasma lipid profile. The aim of our study was to optimize the method for determination of cholesterol in erythrocyte membrane and then to use this method in the determination of cholesterol concentration in erythrocyte membrane in the studied group of blood samples. Cholesterol in erythrocyte membrane was determined in dry lipid extract of erythrocyte membrane by the enzymatic manual CHOD-PAP method. Cholesterol in erythrocyte membrane and plasma lipid parameters (total cholesterol HDL-cholesterol, LDL-cholesterol and triglycerides) were determined in blood samples of 58 females, obtained by routine health control. Lipid parameters were determined by standard biochemical methods. We examined the relationship between cholesterol in erythrocyte membrane and other plasma lipid parameters as well as other atherogenic risk factors (BMI, blood pressure). Optimization of the method for determination of cholesterol in erythrocyte membrane was based on the observation that primary cholesterol standards prepared by dissolving crystal cholesterol cannot be used due to the interference of the dissolved dry extract in organic solvents with the enzymatic reagent. Commercial standard solutions of cholesterol were used for calibration because they contain detergents for solubilisation of the dry extract in enzymatic reagent. The obtained mean value for cholesterol in erythrocyte membrane, as mmol/L erythrocyte is 4.44 ? 1.019; median 4.65 5-th percentile is 2.70, and 95-th percentile is 6.26. In the examined female group we tested cholesterol concentration in erythrocyte membrane according to age. Two groups were formed (females below and above 50 years) using nonparametric t-test no statistically significant difference was found between these two age groups (p>0.05), while plasma lipid parameters of total cholesterol, triglycerides and LDL-cholesterol were different in the examined groups (p<0.05). By Spearmen nonparametric correlation method we found no statistically significant correlation between cholesterol in erythrocyte membrane and other atherogenic risk factors.


2020 ◽  
Vol 14 (7) ◽  
pp. 2423-2433
Author(s):  
Rosalie Nikiema-Ndong ◽  
Aude Syntia Mbang Bengone ◽  
Alexandrine Nsi ◽  
Edwige Nnegue Edzo ◽  
Alvine Sibylle Batou ◽  
...  

L’objectif de cette étude était, de comparer six méthodes de dosage indirect du cholestérol LDL en vue de mettre en place une méthode plus pertinente dans le suivi des modifications cardiométaboliques chez les personnes vivant avec le VIH (PVVIH) sous traitements. Il s’agissait d’une étude prospective descriptive et analytique chez des PVVIH sous antirétroviraux à Libreville, allant du 13 août au 30 novembre 2018. Les patients de plus de 15 ans ont été inclus après avoir donné leurs consentements. Le dosage du cholestérol total, cholestérol HDL, cholestérol LDL et triglycérides a requis un automate multi analyseur (BS 200 de Mindray®) ainsi que des kits « BIOLABO ». La régression linéaire était utilisée pour rechercher les différentes corrélations. Les valeurs de triglycérides <150mg/dL étaient retrouvées chez 96% de la population et 52% avait une concentration de cholestérol HDL <40mg/dL. Les différentes formules de calcul de la concentration du cholestérol LDL par rapport aux  concentrations de LDL cholestérol direct ont montré que le carré du coefficient de corrélation linéaire r était plus élevé pour la formule  d’Anandaraja (r2 = 0,83), suivi de celle de Friedewald avec r2 = 0,72. Un palliatif au dosage direct pourrait être l’utilisation de la formule d’Anandaraja dans notre contexte d’étude.Mots clés : Cholestérol LDL, Cholestérol total, Méthode indirecte, VIH, Anandaraja, Friedewald. Comparison of six indirect LDL cholesterol methods among HIV patients in Libreville   The objective of this study was to compare six methods of indirect measurement of LDL cholesterol for setting a more relevant method of monitoring cardiometabolic changes in people living with HIV under treatment. This was a prospective descriptive and analytic study among people living with HIV and under antiretroviral therapy in Libreville, from 13 August to 30 November 2018. Patients over 15 years of age were included after giving their consent. The dosage total of cholesterol, HDL cholesterol, LDL cholesterol and triglycerides required a multi analyzer BS 200 of Mindray® and reagents kits from BIOLABO. Linear regression was used to found different correlations. Triglyceride values below 150 mg/dL were found among 96% of the population and 52% had HDL cholesterol concentration below 40 mg/dL. The different formulas for calculating the LDL cholesterol concentration relative to the direct LDL cholesterol concentrations show that the square of the linear correlation coefficient r is higher for the Anandaraja formula (r2 = 0.83) followed by that of Friedewald with r2 = 0.72. A palliative method to the direct assay could be the use of Anandaraja's formula in our context.Keywords: LDL cholesterol, Total cholesterol, Indirect method, HIV, Anandaraja, Friedewald.


2013 ◽  
Vol 111 (8) ◽  
pp. 1412-1420 ◽  
Author(s):  
Janne K. Lorenzen ◽  
Søren K. Jensen ◽  
Arne Astrup

Despite a high content of saturated fat, evidence from observational studies indicates that the consumption of dairy products may have a neutral effect or may be inversely associated with the risk of CVD. We aimed to examine whether milk minerals modify the effect of saturated fat on serum lipid profile. We present data from two studies. Study I had a randomised, blinded, parallel design (n 24 pigs) with a 10 d adaptation period during which a high-fat diet was fed to the pigs and a 14 d intervention period during which the same diet either enriched with milk minerals (MM group) or placebo (control group) was fed to the pigs. Study II had a randomised cross-over design (n 9 men) where the subjects were fed either a high-fat diet enriched with milk minerals (MM period) or a regular diet (control period). In both the studies, blood variables were measured before and after the intervention and faecal and urine samples were collected at the end of the dietary periods. The increase in plasma total cholesterol and LDL-cholesterol concentrations but not in HDL-cholesterol concentration was markedly lowered by milk minerals in both the studies. In the animal study, baseline adjusted total cholesterol and LDL-cholesterol concentrations in the MM group were 11 % (P= 0·004) and 13 % (P= 0·03) lower compared with those in the control group after the intervention. Similarly in the human study, baseline adjusted total cholesterol and LDL-cholesterol concentrations were 6 % (P= 0·002) and 9 % (P= 0·03) lower after the MM period compared with those in the control period. HDL-cholesterol concentration was not lowered by milk minerals. These short-term studies indicate that the addition of milk minerals to a high-fat diet to some extent attenuates the increase in total cholesterol and LDL-cholesterol concentrations, without affecting HDL-cholesterol concentration.


2012 ◽  
Vol 62 (1) ◽  
pp. 115-122 ◽  
Author(s):  
Vesna Vrca ◽  
Ljiljana Mayer ◽  
Franjo Škreb ◽  
Dario Rahelić ◽  
Srećko Marušić

Antioxidant supplementation and serum lipids in patients with Graves' disease: Effect on LDL-cholesterol The effect of supplementation with a fixed combination of antioxidants (beta-carotene, selenium, vitamins C and E) on serum lipids was monitored in patients with newly detected Graves' disease. Measurements were made prior to the commencement of therapy and after 30 and 60 days. Patients were randomized into two groups. Test group comprised patients who received antioxidant supplementation in addition to methimazole, while patients treated with methimazole only were in the control group. The concentration of total and HDL-cholesterol increased significantly in test and control groups (p < 0.05) but these groups did not differ significantly. Concentration of LDL-cholesterol increased significantly in the test group only (p < 0.005) and was significantly different from the control group 60 days after the commencement of therapy (p < 0.005). Significant increase in the LDL-cholesterol concentration in the test group requires further investigations.


1999 ◽  
pp. 174-179 ◽  
Author(s):  
GP Leese ◽  
M Wallymahmed ◽  
G Wieringa ◽  
C VanHeyningen ◽  
IA MacFarlane

OBJECTIVE: To determine whether apo E phenotype influences changes in lipid profiles induced by growth hormone replacement in growth hormone (GH)-deficient adults. DESIGNS: Patients were treated for 6 months with recombinant human GH (hGH), given in a dose of 0.125 U/kg per week for 4 weeks followed by 0.25 U/kg per week thereafter. The effects on serum lipids and the influence of apo E phenotype were examined. METHODS: Thirty patients (aged 35.1+/-11.8 years: mean +/- S.D.) with adult growth hormone deficiency with included in the study. Fasting serum samples were analysed for apo E phenotype total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, lipoprotein (a) (Lp(a)) and IGF-I. Low-density lipoprotein (LDL)-cholesterol was calculated using the Friedwald formula. RESULTS: Six months of replacement treatment with hGH resulted in a reduction in HDL-cholesterol from 0.90+/-0.10 to 0.68+/-0.08 mmol/l (P<0.01), and a small, non-significant reduction in total cholesterol from 6.14+/-0.40 to 5.99+/-0.35 mmol/l (P = 0.06). There was no significant change in the other lipid parameters. The decrease in HDL-cholesterol concentration was greater in patients carrying the apo E2 allele (0.40+/-0.07 mmol/l, P<0.05) than in patients homozygous for the apo E3 allele (0.23+/-0.04 mmol/l) and patients carrying the apo E4 allele (0.15+/-0.36 mmol/l). Patients with the apo E4 allele had lower baseline cholesterol concentrations than patients lacking the apo E4 allele, and this persisted after treatment with hGH (P<0.05). CONCLUSIONS: Apo E phenotype may be a determining factor in the response of HDL-cholesterol to hGH in GH-deficient adults.


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