Modelling approach to simulate reductions in LDL cholesterol levels after combined intake of statins and phytosterols/-stanols in humans

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods and Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

A Pharmaceutical Care Program to Improve Adherence to Statin Therapy:A Randomized Controlled Trial

BACKGROUND: Despite the well-known beneficial effects of statins, many patients do not adhere to chronic medication regimens. OBJECTIVE: To implement and assess the effectiveness of a community pharmacy based pharmaceutical care program developed to improve patients' adherence to statin therapy. METHODS: An open-label, prospective, randomized controlled trial was conducted at 26 community pharmacies in the Netherlands. New users of statins who were aged 18 years or older were randomly assigned to receive either usual care or a pharmacist intervention. The intervention consisted of 5 individual counseling sessions by a pharmacist during a 1-year period. During these sessions, patients received structured education about the importance of medication adherence, lipid levels were measured, and the association between adherence and lipid levels was discussed. Adherence to statin therapy was assessed as discontinuation rates 6 and 12 months after statin initiation, and as the medication possession ratio (MPR), and compared between the pharmaceutical care and usual care groups. RESULTS: A total of 899 subjects (439 in the pharmaceutical care group and 460 in the usual care group) were evaluable for effectiveness analysis. The pharmaceutical care program resulted in a significantly lower rate of discontinuation within 6 months after initiating therapy versus usual care (HR 0.66, 95% Cl 0.46 to 0.96). No significant difference between groups was found in discontinuation at 12 months (HR 0.84, 95% Cl 0.65 to 1.10). Median MPR was very high (>99%) in both groups and did not differ between groups. CONCLUSIONS: These results demonstrate the feasibility and effectiveness of a community pharmacy based pharmaceutical care program to improve medication adherence in new users of statins. Frequent counseling sessions (every 3 months) are necessary to maintain the positive effects on discontinuation. Although improvements are modest, the program can be applied easily to a larger population and have a large impact, as the interventions are relatively inexpensive and easy to, implement in clinical practice

Oral intake of added titanium dioxide and its nanofraction from food products, food supplements and toothpaste by the Dutch population

Titanium dioxide (TiO2) is commonly applied to enhance the white colour and brightness of food products. TiO2 is also used as white pigment in other products such as toothpaste. A small fraction of the pigment is known to be present as nanoparticles (NPs). Recent studies with TiO2 NPs indicate that these particles can have toxic effects. In this paper, we aimed to estimate the oral intake of TiO2 and its NPs from food, food supplements and toothpaste in the Dutch population aged 2 to over 70 years by combining data on food consumption and supplement intake with concentrations of Ti and TiO2 NPs in food products and supplements. For children aged 2–6 years, additional intake via ingestion of toothpaste was estimated. The mean long-term intake to TiO2 ranges from 0.06 mg/kg bw/day in elderly (70+), 0.17 mg/kg bw/day for 7–69-year-old people, to 0.67 mg/kg bw/day in children (2–6 year old). The estimated mean intake of TiO2 NPs ranges from 0.19 μg/kg bw/day in elderly, 0.55 μg/kg bw/day for 7–69-year-old people, to 2.16 μg/kg bw/day in young children. Ninety-fifth percentile (P95) values are 0.74, 1.61 and 4.16 μg/kg bw/day, respectively. The products contributing most to the TiO2 intake are toothpaste (in young children only), candy, coffee creamer, fine bakery wares and sauces. In a separate publication, the results are used to evaluate whether the presence of TiO2 NPs in these products can pose a human health risk

A randomized controlled trial of the effect of a pharmaceutical care program on improving adherence to statin therapy:The statin intervention research project (STIPT)

Background: Despite the well-known beneficial effects of statins, many patients do not adhere to chronic medication regimens. Objectives: To assess the efficacy of a pharmaceutical care (PC) program developed to improve patients' adherence. Methods: New users of statins were randomly assigned to receive usual care (UC) or a pharmacist intervention. The intervention consisted of five individual counseling sessions by a pharmacist during a 1-year period. During these sessions, patients received structured education about the importance of medication adherence, lipid levels were measured and the association between adherence and lipid levels was discussed. Adherence to statin therapy was assessed as Abstract of the 26th ICPE 2010 S35 time to discontinuation of treatment and drug-taking compliance (percentage of prescribed drugs actually dispensed). Results: A total of 899 subjects (439 in the PC and 460 in the UC group) were evaluable for efficacy by intention-totreat (ITT), and 853 (393 in the PC and 460 in the UC group) for per-protocol (PP) analysis. The PC program resulted in a significant lower rate of discontinuation within six months after initiating therapy (ITT: HR 0.66, 95% CI: 0.46-0.96; PP: HR 0.53, 95% CI: 0.36-0.80). Twelve months after initiating therapy, this difference in discontinuation rate was only significant in the PP analysis (ITT: HR 0.84, 95% CI: 0.65-1.10; PP: HR 0.73, 95% CI: 0.55-0.97). Drug-taking compliance was very high (>99%) in both the PC and UC group and did not differ between groups. Conclusions: We demonstrated the feasibility and efficacy of a community pharmacy-based PC program to improve medication adherence in new users of statins

Simultaneous intake of oat bran and atorvastatin reduces their efficacy to lower lipid levels and atherosclerosis in LDLr-/- mice

The present study aimed to investigate the effects of separate and simultaneous dietary intake of atorvastatin (ATO) and the soluble fiber oat bran on serum and hepatic lipid levels and the degree of atherosclerosis. Ninety female LDL-receptor-deficient (LDLr-/-) mice were fed a Western-type diet containing either low dose (0.0025%), high dose (0.01%) or no ATO, with or without oat bran (27%) (n = 15 per group) for 16 weeks. Both ATO and oat bran were effective in reducing serum total cholesterol levels (low ATO: -5.48, high ATO: -9.12, oat bran: -3.82 mmol/l, compared to control (no ATO/no oat bran), all p < 0.0001). When oat bran was added to a low dose ATO, the cholesterol-lowering effects of this combination were 50% smaller compared to the low dose ATO diet alone (between-group difference: 2.77 mmol/l, p = 0.002), whereas total cholesterol decreased to a similar extent in the groups fed a high dose ATO, with or without oat bran (between-group difference: 1.10 mmol/l, p = 0.21). Serum LDL- and HDL-cholesterol, triglycerides, hepatic lipid levels and atherosclerotic lesion development showed a similar pattern. In conclusion, the efficacy of oat bran and atorvastatin to lower lipid levels and atherosclerosis is reduced after simultaneous intake. We hypothesize that oat bran inhibits the intestinal absorption of atorvastatin, and consequently its cholesterol-lowering effects. The effects are likely dependent on the type of statin and dietary fiber, and on the relative timing of intake of the statin and the dietary fiber. Future studies should focus on these aspects to provide further insight into the exact mechanism of this food-drug interaction. (C) 2011 Elsevier Ltd. All rights reserved