Modelling approach to simulate reductions in LDL cholesterol levels after combined intake of statins and phytosterols/-stanols in humans.
BACKGROUND
To examine the effects on LDL cholesterol of the combined use of statins and phytosterols/-stanols, in vivo studies and clinical trials are necessary. However, for a better interpretation of the experimental data as well as to possibly predict cholesterol levels given a certain dosing regimen of statins and phytosterols/-stanols a more theoretically based approach is helpful. This study aims to construct a mathematical model to simulate reductions in low-density lipoprotein (LDL) cholesterol in persons who combine the use of statins with a high intake of phytosterols/-stanols, e.g. by the use of functional foods.


RESULTS
The proposed model includes the cholesterol pool size in the liver and serum levels of very low-density lipoprotein (VLDL) cholesterol. Both an additional and a multiplicative effect of phytosterol/-stanol intake on LDL cholesterol reduction were predicted from the model. The additional effect relates to the decrease of dietary cholesterol uptake reduction, the multiplicative effect relates to the decrease in enterohepatic recycling efficiency, causing increased cholesterol elimination through bile. From the model, it was demonstrated that a daily intake of 2 g phytosterols/-stanols reduces LDL cholesterol level by about 8% to 9% on top of the reduction resulting from statin use. The additional decrease in LDL cholesterol caused by phytosterol/-stanol use at the recommended level of 2 g/d appeared to be similar or even greater than the decrease achieved by doubling the statin dose.


CONCLUSIONS
We proposed a simplified mathematical model to simulate the reduction in LDL cholesterol after separate and combined intake of statins and functional foods acting on intestinal (re)absorption of cholesterol or bile acids in humans. In future work, this model can be extended to include more complex (regulatory) mechanisms.
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
Simone R B M
SR
Eussen
Cathy J M
CJ
Rompelberg
Olaf H
OH
Klungel
Jan C H
JC
van Eijkeren
D000465:Algorithms; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D050171:Dyslipidemias / Q000097:blood*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008954:Models, Biological; D010840:Phytosterols / Q000494:pharmacology*; D008517:Phytotherapy; D011758:Pyrroles / Q000494:pharmacology*
D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D010840:Phytosterols; D011758:Pyrroles; D000069059:Atorvastatin