Mogelijkheden voor reductie van medicijngebruik door gezonde voeding(sproducten) in zorginstellingen

De nadruk van dit rapport ligt op de volgende twee vragen: 1) In hoeverre kan voeding het gebruik van geneesmiddelen in het algemeen in verpleeghuizen beïnvloeden? Hierbij valt onderscheid te maken in: a) Wat is de rol van omgevingsinvloeden (sociale context)? b) Voedingsproducten: welke specifieke producten kunnen medicijngebruik verminderen? 2) Wat is de kostenefficiëntie van de vervanging van medicijnen door gezonde voedingsproducten? In hoeverre betekent investeren in voeding een besparing op medicijnen of verpleging

Foliumzuurverrijking: zowel preventie als bevordering van kanker

In many countries foods are fortified with folic acid to prevent neuraltube defects. Beneficial effects on cancer, cardiovascular diseases and dementia are also assumed. As well as beneficial effects, harmful effects may also occur. In addition to masking vitamin-B12 deficiency, there is some evidence that folic acid may promote progression of established tumours in laboratory animals and humans. In addition, it has been hypothesized that fortification with folic acid may have further negative effects on cancer through genetic selection. Given the high prevalence of cancer, these potentially harmful effects should also be taken into account in the Dutch debate on the advantages and disadvantages of folic acid fortificatio

Health benefits and costs of functional foods with phytosterols/-stanols in addition to statins in the prevention of cardiovascular disease

The Dutch guidelines for cardiovascular risk management recommend that all persons with a 10-year SCORE risk ≥5% should be given lifestyle recommendations, including encouragement of the use of phytosterols/-stanols as part of a healthy diet. Treatment with a statin is recommended for all persons with a 10-year SCORE risk of fatal cardiovascular disease (CVD) ≥10%. In the Netherlands the detection of high cholesterol values and other CVD risk factors occurs primarily through clinical case finding. The current study aimed to assess whether functional foods enriched with phytosterols/-stanols add to the benefits of statins in terms of effects and costs. Cost-effectiveness of bread spread with phytosterols/-stanols (PS) was evaluated both in a 'case-findingsituation' and in a hypothetical 'universal screening-situation' (assuming free population-based screening resulting in known SCORE risks). We compared two scenarios per situation: One with and one without additional PS use in all subjects that were known to qualify according to the guidelines. Since many people discontinue the use of PS and statins in the first two year we included discontinuation rates for new users based on empirical data. Long term health benefits were estimated using the RIVM Chronic Disease Model and measured in terms of Quality Adjusted Life Years (QALYs) gained. This simulation model also gave estimates for long term differences in health care costs between the scenarios. Intervention costs were estimated bottom-up from resource use and Dutch unit costs. Finally, health care and intervention costs per QALY were calculated and compared with standards for cost effectiveness. Uncertainty of these outcomes will be assessed using probabilistic sensitivity analysis. Preliminary results showed that addition of phytosterols/-stanols was not cost-effective, meaning that the costs of the addition were relatively high compared to the health gains

Effect of eugenol on the genotoxicity of established mutagens in the liver

The influence of in vivo treatment with eugenol on established mutagens was studied to determine whether eugenol has antigenotoxic potential. The effects of eugenol in rats was investigated in the unscheduled DNA synthesis (UDS) assay with established mutagens and the Salmonella typhimurium mutagenicity assay. In addition, the effect of in vitro treatment with eugenol on benzo[a]pyrene (B[a]P)-induced genotoxicity in human hepatoma cell line Hep G2 was investigated in the single-cell gel electrophoresis assay. The mutagenicity of B[a]P in the S. typhimurium mutagenicity assay was lower in liver S-9 fractions prepared from rats treated with eugenol orally (1000 mg/kg body weight) than in liver S-9 fractions from control rats. Incubation of liver S-9 fractions from eugenol-treated rats with dimethylbenzanthracene (DMBA) had no antimutagenic effect. Eugenol did not modify UDS activity in hepatocytes isolated from rats pretreated with eugenol orally after exposure of these cells in vitro to DMBA and aflatoxin B1. Four different treatment schemes of combinations of B[a]P and eugenol were examined in Hep G2 cells: pre-treatment with eugenol; simultaneous treatment with eugenol and B[a]P; a combination of these (pretreatment/simultaneous treatment); and post-treatment with eugenol. An increase in the genotoxicity of B[a]P was found in Hep G2 cells. No effect of eugenol on the genotoxicity of B[a]P was found with the pre- and post-treatments. It is concluded that the effect of eugenol on genotoxicity induced by established mutagens is not univocal: in vivo treatment of rats with eugenol resulted in a reduction of the mutagenicity of B[a]P in the S. typhimurium mutagenicity assay, while in the UDS assay no effect of eugenol was found. In vitro treatment of cultured cells with eugenol resulted in an increase in genotoxicity of B[a]P. These findings indicate that there is only limited support for the antigenotoxic potential of eugenol in vivo

Effects of n-3 fatty acids on major cardiovascular events in statin users and non-users with a history of myocardial infarction

Aims Recent secondary prevention trials have failed to demonstrate a beneficial effect of n-3 fatty acids on cardiovascular outcomes, which may be due to the growing use of statins since the mid-1990s. The aim of the present study was to assess whether statins modify the effects of n-3 fatty acids on major adverse cardiovascular events in patients with a history of myocardial infarction (MI). Methods and results Patients who participated in the Alpha Omega Trial were divided into consistent statin users (n = 3740) and consistent statin non-users (n = 413). In these two groups of patients, the effects of an additional daily amount of 400 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA), 2 g a-linolenic acid (ALA), or both on major cardiovascular events were evaluated. Multivariable Cox's proportional hazard models were used to calculate adjusted hazard rate ratios (HRadj). Among the statin users 495 (13%) and among the statin non-users 62 (15%) developed a major cardiovascular event. In statin users, an additional amount of n-3 fatty acids did not reduce cardiovascular events [HRadj 1.02; 95% confidence interval (CI): 0.80, 1.31; P = 0.88]. In statin non-users, however, only 9% of those who received EPA–DHA plus ALA experienced an event compared with 18% in the placebo group (HRadj 0.46; 95% CI: 0.21, 1.01; P= 0.051). Conclusion In patients with a history of MI who are not treated with statins, low-dose supplementation with n-3 fatty acids may reduce major cardiovascular events. This study suggests that statin treatment modifies the effects of n-3 fatty acids on the incidence of major cardiovascular events

Effect of eugenol on the mutagenicity of benzo[a]pyrene and the formation of benzo[a]pyrene-DNA adducts in the X-lacZ-transgenic mouse.

To study the possible reduction by eugenol of the mutagenicity and genotoxicity of benzoja]pyrene (B[a]P) in vivo, the X-lacZ-transgenic mouse strain 40.6 (Muta(TM)Mouse) was used. Male mice were fed a diet containing 0.4% (w/w) eugenol or a control diet for 58 days. On day 10, half of the mice received an i.p. dose of 100 mg/kg b.w. B[a]P. The lacZ mutants were recovered by packaging of DNA isolated from liver into lambda phage, and expressed in E. coli C lacZ- recA-galE- bacteria. In both control mice and mice fed the eugenol diet, B[a]P treatment resulted in a similar, significant increase in lacZ mutant frequency. Eugenol was not mutagenic by itself By 32P-postlabelling analysis of the liver DNA using an analysis method with chromatographic conditions for B[a]P-DNA adducts, no effect of eugenol on the formation of B[a]P-DNA adducts in the λ-lacZ-transgenic mouse was found. By 32P-postlabelling analysis using an alkenylbenzene solvent system the amount of B[a]P-DNA adducts was lower in mice fed the eugenol diet than in mice fed the control diet but the decrease was not statistically significant. However, one spot indicative of an eugenol-associated DNA adduct was detected. The present data provide no evidence for antimutagenic or antigenotoxic potential of eugenol in vivo Furthermore, they suggest genotoxicity in vivo of eugenol per se

Inhibition of rat, mouse, and human glutathione S-transferase by eugenol and its oxidation products

The irreversible and reversible inhibition of glutathione S-transferases (GSTs) by eugenol was studied in rat, mouse and man. Using liver cytosol of human, rat and mouse, species differences were found in the rate of irreversible inhibition of GSTs by eugenol in the presence of the enzyme tyrosinase. Tyrosinase was used to oxidize eugenol. No inhibition was observed in the absence of tyrosinase. The rate of irreversible inhibition of GSTs was highest in mouse cytosol, and lowest in rat cytosol. In addition, the irreversible inhibition of human and rat GSTs by eugenol was studied using purified isoenzymes of man and rat. The human GST isoenzymes A1-1, M1a-1a and P1-1 and the rat GST isoenzymes 1-1, 2-2, 3-3, 4-4 and 7-7 were irreversibly inhibited by eugenol in the presence of tyrosinase. In this respect human GST P1-1 and rat GST 7-7 were by far the most sensitive enzymes; human GST A2-2 was not inhibited. indications were found that human GST P1-1 may be inhibited via three mechanisms: in addition to the well documentated nucleophilic addition of quinones and oxidation of cysteine residues, a covalent subunit cross-linking was also observed. The reversible inhibition of human and rat GST by eugenol, eugenol methyl ether, isoeugenol methyl ether, 2-allylphenol and 4-propylphenol was also studied using purified isoenzymes. The reversible inhibition of human and rat GSTs, using 1-chloro-2,4-dinitrobenzene as substrate, was expressed as It, All compounds caused moderate reversible inhibition (I25 ranged from 0.2 to 5.4 mM for human GSTs and from 0.4 to 4.9 mM for rat GSTs). In rat, eugenol methyl ether was the strongest inhibitor. In human, the overall inhibiting capacities of eugenol, eugenol methyl ether, isoeugenol methyl ether and 4-propyl phenol were more or less similar; 2-allylphenol was the poorest inhibitor. Chemicals/CAS: 2-allylphenol, 1745-81-9; 4-propylphenol, 645-56-7; Allyl Compounds; Eugenol, 97-53-0; Glutathione Transferase, EC 2.5.1.18; Isoenzymes; isoeugenol, 97-54-1; methyleugenol, 93-15-2; Monophenol Monooxygenase, EC 1.14.18.1; Phenol

Mogelijkheden voor reductie van medicijngebruik door gezonde voeding(sproducten) in zorginstellingen

De nadruk van dit rapport ligt op de volgende twee vragen: 1) In hoeverre kan voeding het gebruik van geneesmiddelen in het algemeen in verpleeghuizen beïnvloeden? Hierbij valt onderscheid te maken in: a) Wat is de rol van omgevingsinvloeden (sociale context)? b) Voedingsproducten: welke specifieke producten kunnen medicijngebruik verminderen? 2) Wat is de kostenefficiëntie van de vervanging van medicijnen door gezonde voedingsproducten? In hoeverre betekent investeren in voeding een besparing op medicijnen of verpleging