Presence and levels of galactosyllactoses and other oligosaccharides in human milk and their variation during lactation and according to maternal phenotype

Among the human milk oligosaccharides (HMOS), the galactosyllactoses (GLs) are only limitedly studied. This study aims to describe the presence and relative levels of HMOS, including GLs, in human milk (HM) according to maternal Secretor and Lewis (SeLe) phenotype and lactation stage. Relative levels of 19 HMOS were measured in 715 HM samples collected in the first 4 months postpartum from 371 donors participating in the PreventCD study. From a subset of 24 Dutch women (171 HM samples), samples were collected monthly up to 12 months postpartum and were additionally analyzed for relative and absolute levels of beta 6 '-GL, beta 3 '-GL and alpha 3 '-GL. Maternal SeLe phenotype or HM group was assigned based on the presence of specific fucosylated HMOS. Most HMOS, including beta 6 '- and beta 3 '-GL, were present in the vast majority (>= 75%) of HM samples, whereas others (e.g., LNDFH II, 2 '-F-LNH and alpha 3 '-GL) only occurred in a low number (<25%) of samples. Clear differences were observed between the presence and relative levels of the HMOS according to the maternal phenotype and lactation stage. Absolute concentrations of beta 6 '-GL and beta 3 '-GL were higher in HM group IV samples compared to samples of the other three HM groups. beta 3 '-GL was also higher in HM group II samples compared to HM group I samples. beta 3 '-GL and beta 6 '-GL were stable over lactation stages. In conclusion, presence and levels of HMOS vary according to HM group and lactation stage. Not all HMOS behave similarly: some HMOS depend strongly on maternal phenotype and/or lactation stage, whereas others do not. beta 3 '-GL and beta 6 '-GL were present in low concentrations in over 75% of the analyzed HM samples and showed differences between HM groups, but not between the lactation stages.Transplantation and immunomodulatio

The food-pharma interface: consequences of combined use of functional foods and statins

It is increasingly being recognised that most chronic diseases are multifactorial in origin. The focus of this thesis was cardiovascular disease (CVD), a multifactorial disease in which a combination of genetic and environmental factors contributes to the aetiology and progression of the disease. To control multifactorial diseases, a treatment approach in which medicines and nutrition complement each other may prove to be the most successful. In the domain of nutrition, apart from (disease-related) dietetic regimes, an increasing number of functional foods and dietary supplements, each with their own health claim, are marketed. These food items are considered to be positioned between traditional foods and medicines at the so-called ‘Food-Pharma interface’. The attention of the European Union regarding functional foods and dietary supplements has been principally directed to food safety and (claims of) efficacy, and most of the research focuses on these two areas. Currently little is known about physiological or behavioural interactions between functional foods or dietary supplements and pharmaceuticals. This thesis aims to start filling the gaps in knowledge in this field and adds to our understanding of the beneficial and harmful effects of the combined use of functional foods/dietary supplements and medicines. The present thesis shows that the use of functional foods and dietary supplements may offer opportunities to reduce health risk factors when combined with prescription drugs. We have shown that functional foods enriched with phytosterols/-stanols lower total and LDL cholesterol by 4% and 5%, respectively, when used in combination with statins in a real-life setting. At the moment, however, it is not clear whether these reductions in cholesterol levels lead to a reduced CVD risk. For functional foods enriched with n-3 polyunsaturated fatty acids (n-3 PUFA) it was found that patients on statin therapy were at a relatively low risk of future cardiovascular events, such that supplementation with n-3 PUFA did not provide additional protection against cardiovascular events. There are also potential problems related to the use of functional foods and dietary supplements. First, their use may increase the risk for physiological food-drug interactions due to the elevated amounts of specific functional ingredients in the diet. In an experimental animal study, it was shown that the cholesterol-lowering effect of statins was reduced when oat beta-glucans were present in the diet of female LDL-receptor deficient mice. Second, we showed that the use of functional foods or dietary supplements may lead people to indulge in self-medication, resulting in lower adherence to drug therapy. Research towards this behavioural interaction is currently lacking and will become more important in the future as the world market for functional foods and dietary supplements is growing

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

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

Different elemental infant formulas show equivalent phosphorus and calcium bioavailability in healthy volunteers

Retrospective chart reviews have reported hypophosphatemia associated with elemental formula use in infants and children with systemic disease involving multiple diagnoses. The present study aims to evaluate the bioavailability of phosphorus from 2 commercial elemental formulas and to test our hypothesis of bioequivalence of the 2 products in healthy volunteers receiving gastric acid-suppressive medication. A single-center, double-blind, randomized, cross-over study was conducted in healthy volunteers with esomeprazole-induced hypochlorhydria. After a standardized low phosphorus meal followed by overnight fasting, subjects consumed 1 gram of phosphorus in a single oral dose of 1217 kcal of Product A (Neocate) or Product B (Elecare). The alternate product was given following a 1-week washout period. Blood and urine were collected at baseline and different time-points for up to 6 hours after product consumption. Area-under-the-curve (AUC) and peak values (C-peak) for serum phosphate and calcium and urinary creatinine-corrected phosphate and calcium were assessed for bioequivalence of Products A and B. Results show that the geometric mean ra tio (GMR) and 90% CI for serum phosphate were 1.041 (0.998-1.086) and 1.020 (0.963-1.080) for AUC(0-360) and C-peak, respectively, meeting the predetermined criteria for bioequivalence. Urinary creatinine-corrected phosphate followed a similar pattern after intake of Product A and B, but did not reach bioequivalence criteria (GMR: AUC(70-370) = 1.105 (0.918-1.330); C-peak = 1.182 (1.040-1.343)). Serum calcium concentrations (GMR: AUC(0-360) = 1.002 (0.9961.009); C-peak = 0.991 (0.983-0.999)) and urinary creatinine-corrected calcium excretion (GMR: AUC(70-370) = 1.117 (1.023-1.219); C-peak = 1.157 (1.073-1.247)) demonstrated bioequivalence of the products. In conclusion, both elemental infant formulas showed equivalent serum phosphorus and calcium bioavailability in healthy volunteers even if combined with treatment with acid-suppressive medication. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/

Iron and vitamin D defiency in healthy young children in Western-Europe despite current nutrional recommendations

BACKGROUND AND AIM: Iron deficiency (ID) and vitamin D deficiency (VDD) are the 2 most common micronutrient deficiencies in young children worldwide and may lead to impaired neurodevelopment and rickets, respectively. Risk factors for ID and VDD differ between populations. The objective of this study was to determine the prevalence of and risk factors for ID and VDD in 12- to 36-month-old children in Western Europe. METHODS: This study took place in Germany, the Netherlands, and the United Kingdom from 2012 to 2014. A venous blood sample was taken to establish iron and vitamin D status. ID was defined as serum ferritin <12 μg/L in the absence of infection (high sensitivity C-reactive protein <10 mg/L). VDD was defined as serum 25-hydroxyvitamin D <50 nmol/L (20 ng/mL). Furthermore, parents were asked to fill out a questionnaire regarding their child's demographic- and socioeconomic characteristics, food intake, sun exposure, and medical history. RESULTS: In 325 children (white race 95%, boys 56%, mean age 20.7 months) the overall prevalence of ID and VDD was 11.8% and 22.8%, respectively. The use of primarily cow's milk as major type of milk was associated with ID (odds ratio [OR] 3.20, 95% confidence interval [CI] 1.12-8.53) and VDD (OR 7.17, 95% CI 3.10-16.57). The use of vitamin D supplements (OR 0.20, 95% CI 0.07-0.56) was associated with a lower prevalence of VDD. CONCLUSION: Despite current nutritional recommendations, ID and VDD are common in healthy young white children. Health programs focusing on adequate iron and vitamin D intake at an early age should be implemented to prevent deficiencies

Supplementary Material for: Theoretical Impact of Replacing Whole Cow's Milk by Young-Child Formula on Nutrient Intakes of UK Young Children: Results of a Simulation Study

<b><i>Background:</i></b> Research into the role of young-child formulae (YCF) in a child's diet is limited and there is no consensual recommendation on its use. We evaluated the theoretical nutritional impact of replacing the existing practice of consuming cow's milk by YCF. <b><i>Methods:</i></b> From the UK Diet and Nutrition Survey of Infants and Young Children, whole cow's milk consumers, aged 12-18 months (n = 591) were selected for simulation scenarios. In Scenario 1, we tested the replacement of all whole cow's milk (434 ± 187 ml/day) by a matching volume of YCF, and in Scenario 2, all whole cow's milk was replaced by the on-pack recommended daily intake of 300 ml. Nutrient intakes before and after simulation scenarios were compared and evaluated against nutrient recommendations. <b><i>Results:</i></b> Intakes of protein and saturated fatty acids were significantly decreased, whereas essential fatty acid intakes were increased. The prevalence of nutrient inadequacy before simulation was 95.2% for vitamin D and 53.8% for iron. After simulation, inadequacy decreased to 4.9% (Scenario 1) and 0% (Scenario 2) for vitamin D and to 2.7% (Scenario 1) and 1.1% (Scenario 2) for iron. <b><i>Conclusions:</i></b> Replacement of habitual cow's milk intake by a matching volume or 300 ml of YCF may lead to nutritional intakes more in line with recommendations in young children

Costs and health effects of adding functional foods containing phytosterols/-stanols to statin therapy in the prevention of cardiovascular disease

The present modelling study aimed to evaluate if and by how much functional foods containing phytosterols/-stanols add to the benefits of statins in the prevention of cardiovascular disease in terms of cost-effectiveness. Long-term health effects, measured as quality-adjusted life-years gained, and costs for scenarios with additional phytosterol/-stanol use were compared to scenarios without extra use. Phytosterols/-stanols were given only to persons who were eligible for use according to their 10-year absolute risk of fatal cardiovascular disease (SCORE-risk). Intake levels and discontinuation rates as observed in daily practice were included in the model. Two situations were compared: 1) A real-life situation in which persons at high SCORE-risk were identified through clinical case-finding and, 2) A theoretical maximum situation where universal screening was implemented resulting in known SCORE-risks for the whole Dutch population aged 35-75 years (8.4 million people). Sensitivity analyses were performed for variations in the cholesterol-lowering effect and intake level of phytosterols/-stanols, indirect health care costs, time horizon and discount rates. At the model's start year, a total of 1.0 (real-life situation) to 3.3 (maximum situation) million persons qualified for phytosterol/-stanol use based on their SCORE-risk (both statin users and statin non-users). Over the model's time horizon, this resulted in a gain of 2700 to 16,300 quality-adjusted life-years, and yielded cost-effectiveness ratios that ranged between (sic)92,000 and (sic)203,000 per quality-adjusted life-year. This simulation study showed that the cost-effectiveness of phytosterols/-stanols as monotherapy and as add-on to statins is above thresholds for cost-effectiveness, generally ranging between (sic)20,000 and (sic)50,000, and is thus a non-cost-effective strategy to reduce cardiovascular disease. (C) 2011 Elsevier B.V. All rights reserved

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

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

Purpose 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. Methods We used data from the statin intervention research project, a randomized controlled trial aimed at improving adherence to statins. In the trial, new statin users were randomized to receive either usual care or extensive pharmaceutical care consisting of five individual counseling sessions. Customary use of phytosterol/-stanol-enriched products was identified by questionnaires filled out by all participants. Automated pharmacy-dispensing records were used to assess adherence in terms of discontinuation of therapy and the medication possession ratio. Analyses were performed for the overall population, as well as stratified for receiving pharmaceutical or usual care. Results The use of functional foods enriched with phytosterols/-stanols was not related to discontinuation of statin therapy, neither in the overall population (overall population adjusted hazard rate ratio (HR(adj)): 0.80 [95% CI: 0.59-1.08]), nor when stratified by randomization arm (pharmaceutical care HR(adj): 0.77 [95% CI: 0.49-1.23]); usual care HR(adj): 0.81 [95% CI: 0.54-1.21]). The median medication possession ratio was significantly lower in users of phytosterols/-stanols in the usual care group, but the difference was not clinically relevant. Conclusions Customary use of phytosterol/-stanol-enriched functional foods did not affect adherence to statins in new users that are well informed on the beneficial effects of statin therapy. In daily medical practice, general practitioners and pharmacists should urge subjects not to take phytosterol/-stanol-enriched functional foods as replacement for their prescribed medication. Copyright (C) 2011 John Wiley & Sons, Ltd