Simone R.B.M. Eussen

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 α-linolenic acid (ALA), or both on major cardiovascular events were evaluated. Multivariable Coxs proportional hazard models were used to calculate adjusted hazard rate ratios (HR(adj)). 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 [HR(adj) 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 (HR(adj) 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.

Iron intake and status of children aged 6-36 months in Europe: a systematic review.

Background: Iron deficiency is the most common nutritional disorder in the world. Young children are particularly vulnerable to the consequences of iron deficiency because of their rapidly developing brain. This review evaluates the prevalence of inadequate iron intake and iron deficiency (anaemia) in European children aged 6-36 months. Summary: Computerized searches for relevant articles were performed in November 2013. A total of 7,297 citations were screened and 44 studies conducted in 19 European countries were included in this review. In both infants (6-12 months) and young children (12-36 months), the mean value of iron intakes in most countries was close to the RDA. Nevertheless, proportions of inadequate intakes were considerable, ranging from about 10% in the Netherlands up to 50% in Austria, Finland and the United Kingdom. The prevalence of iron deficiency varied between studies and was influenced by childrens characteristics. Two to 25% of infants aged 6-12 months were found to be iron deficient, with a higher prevalence in those who were socially vulnerable and those who were drinking cows milk as a main type of drink in their first year of life. In children aged 12-36 months, prevalence rates of iron deficiency varied between 3 and 48%. Prevalence of iron deficiency anaemia in both age groups was high in Eastern Europe, as high as 50%, whereas the prevalence in Western Europe was generally below 5%. Key Messages: In most European countries, mean iron intakes of infants and children aged 6 to 36 months were found to be close to the RDA. Nevertheless, high proportions of inadequate intakes and high prevalence rates of iron deficiency were observed. Health programs should (keep) focus(ing) on iron malnutrition by educating parents on food choices for their children with iron-rich and iron-fortified foods, and encourage iron supplementation programmes where iron intakes are the lowest.

Dose-dependent cholesterol-lowering effects of phytosterol/phytostanol-enriched margarine in statin users and statin non-users under free-living conditions

OBJECTIVE To assess the effectiveness (extent to which an intervention works in daily medical practice) of the use of phytosterol/phytostanol-enriched margarines to lower total and non-HDL cholesterol levels in users and non-users of statins. DESIGN Retrospective cohort study. SETTING Data were obtained from questionnaires on health and food intake from a population-based longitudinal cohort linked to pharmacy-dispensing records. SUBJECTS The analysis included 3829 men and women (aged 31-71 years) who were examined during 1998-2002 and re-examined at 5-year follow-up during 2003-2007. RESULTS Recommended doses of margarines were consumed by only 9 % of the subjects. Serum total cholesterol decreased by respectively -0·16 (95 % CI -0·26, -0·05) mmol/l, -1·40 (95 % CI -1·51, -1·30) mmol/l and -1·64 (95 % CI -1·91, -1·37) mmol/l in subjects who started to use phytosterols/phytostanols only, statins only or a combination of both compounds at some point in time between examination and re-examination, compared with subjects who did not start using phytosterols/phytostanols or statins. Cholesterol-lowering effects of the phytosterols/phytostanols were similar in statin users and statin non-users and increased with increasing intake of enriched margarine (no intake, 0; low intake, -0·017 (95 % CI -0·16, 0·13) mmol/l; medium intake, -0·089 (95 % CI -0·22, 0·038) mmol/l; high intake, -0·32 (95 % CI -0·50, -0·14) mmol/l). CONCLUSIONS Although recommended intake levels of the enriched margarines were not reached by all persons, these data show that under customary conditions of use phytosterols/phytostanols are effective in lowering cholesterol levels in both statin users and non-users.

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.

Influence of the use of functional foods enriched with phytosterols/-stanols on adherence to statin therapy

Subjects using functional foods with approved health claims may be more likely to be non‐adherent with prescribed drug therapy. This study aimed to assess the influence of the use of phytosterol/‐stanol‐enriched functional foods on adherence to statin therapy among patients initiating treatment.

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

BackgroundTo 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.Methods and ResultsThe 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.ConclusionWe 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.

Systematic Review on N-3 and N-6 Polyunsaturated Fatty Acid Intake in European Countries in Light of the Current Recommendations - Focus on Specific Population Groups

Background: Earlier reviews indicated that in many countries adults, children and adolescents consume on an average less polyunsaturated fatty acids (PUFAs) than recommended by the Food and Agriculture Organisation/World Health Organisation. Summary: The intake of total and individual n-3 and n-6 PUFAs in European infants, children, adolescents, elderly and pregnant/lactating women was evaluated systematically. Results: The evaluations were done against recommendations of the European Food Safety Authority. Key Messages: Fifty-three studies from 17 different European countries reported an intake of total n-3 and n-6 PUFAs and/or individual n-3 or n-6 PUFAs in at least one of the specific population groups: 10 in pregnant women, 4 in lactating women, 3 in infants 6-12 months, 6 in children 1-3 years, 11 in children 4-9 years, 8 in adolescents 10-18 years and 11 in elderly >65 years. Mean linoleic acid intake was within the recommendation (4 energy percentage [E%]) in 52% of the countries, with inadequate intakes more likely in lactating women, adolescents and elderly. Mean α-linolenic acid intake was within the recommendation (0.5 E%) in 77% of the countries. In 26% of the countries, mean eicosapentaenoic acid and/or docosahexaenoic acid intake was as recommended. These results indicate that intake of n-3 and n-6 PUFAs may be suboptimal in specific population groups in Europe.

Nutritional challenges and opportunities during the weaning period and in young childhood.

The early years of life are a period of very rapid growth and development. In this critical phase, food preferences are formed which carry over into childhood and beyond and foundations are laid for a healthy adult life. Excess energy, imbalances in macronutrient quality, and nutritional deficiencies may form inappropriate nutritional signals, leading to metabolic disturbances and affecting the obesity risk. For instance, the intake of protein and sugar-sweetened beverages in young children has been associated with an increased risk of overweight and obesity. In reality, scientific reports have shown that the dietary intakes of vegetables, α-linolenic acid, docosahexaenoic acid, iron, vitamin D, and iodine are low and the intakes of protein, saturated fatty acids, and added sugar are high in young children living in Europe. A focus on improving feeding habits and approaches to support more balanced nutritional intakes early in life may have significant public health benefits.

Effects of the use of phytosterol/‐stanol‐enriched margarines on adherence to statin therapy

The use of margarines enriched with phytosterols or phytostanols is recommended as an appropriate adjunctive therapy for patients with certain lipid profiles, but may result in a behavioral modification leading to a change in persons adherence to lipid‐lowering drug treatment. This study aimed to examine the influence of the use of margarines enriched with phytosterols/‐stanols on adherence to statin therapy.

A micronutrient-fortified young-child formula improves the iron and vitamin D status of healthy young European children: a randomized, double-blind controlled trial

BACKGROUND Iron deficiency (ID) and vitamin D deficiency (VDD) are common among young European children because of low dietary intakes and low compliance to vitamin D supplementation policies. Milk is a common drink for young European children. Studies evaluating the effect of milk fortification on iron and vitamin D status in these children are scarce. OBJECTIVE We aimed to investigate the effect of a micronutrient-fortified young-child formula (YCF) on the iron and vitamin D status of young European children. DESIGN In this randomized, double-blind controlled trial, healthy German, Dutch, and English children aged 1-3 y were allocated to receive either YCF (1.2 mg Fe/100 mL; 1.7 μg vitamin D/100 mL) or nonfortified cow milk (CM) (0.02 mg Fe/100 mL; no vitamin D) for 20 wk. Blood samples were taken before and after the intervention. The primary and secondary outcomes were change from baseline in serum ferritin (SF) and 25-hydroxyvitamin D [25(OH)D], respectively. ID was defined as SF <12 μg/L in the absence of infection (high-sensitivity C-reactive protein <10 mg/L) and VDD as 25(OH)D <50 nmol/L. Statistical adjustments were made in intention-to-treat analyses for sex, country, age, baseline micronutrient status, and micronutrient intake from food and supplements (and sun exposure in the case of vitamin D outcomes). RESULTS The study sample consisted of 318 predominantly Caucasian (∼95%) children. The difference in the SF and 25(OH)D change between the treatment groups was 6.6 μg/L (95% CI: 1.4, 11.7 μg/L; P = 0.013) and 16.4 nmol/L (95% CI: 9.5, 21.4 nmol/L; P < 0.001), respectively. The probability of ID (OR 0.42; 95% CI:0.18, 0.95; P = 0.036) and VDD (OR 0.22; 95% CI: 0.01, 0.51; P < 0.001) after the intervention was lower in the YCF group than in the CM group. CONCLUSION Micronutrient-fortified YCF use for 20 wk preserves iron status and improves vitamin D status in healthy young children in Western Europe. This trial was registered at www.trialregister.nl as NTR3609.