Micronutrient intakes in the Dutch diet: foods, fortified foods and supplements in a cross sectional study.

PURPOSE: This study investigates intakes of risk micronutrients from non-fortified foods, fortified foods and food supplements in different age and gender sub-groups of the Dutch population. METHODS: This is a secondary analysis of the Dutch National Food Consumption Survey (DNFCS 2012-2016, N = 4313, 1-79 years). The proportion of the population with Habitual Intakes below the Estimated Average Requirement (EAR) and above the Upper Level (UL) for calcium, iron, zinc, vitamin A, vitamin B6, folate, vitamin D and vitamin E from non-fortified foods, fortified foods and total intake including food supplements was calculated using Statistical Program to Assess Dietary Exposure (SPADE). RESULTS: More than 50% of the population had an intake below the EAR for calcium, iron, vitamin D and folate. Intakes were inadequate for certain sub-groups for the other vitamins and minerals. Adolescents and women were the population sub-groups most likely to have an intake below the EAR. For zinc, vitamin A and folic acid, more than 1% of toddlers exceeded the UL from the total intake. A negligible proportion exceeded the UL for the other vitamins and minerals. CONCLUSION: Inadequate intakes were found for several micronutrients in various population sub-groups despite an apparently well-nourished population. Intakes of zinc, folic acid and vitamin A from food supplements in toddlers and preschoolers should be investigated further to ensure they do not exceed recommended amounts. These results can be used to inform policy makers and to design nutritional interventions to improve micronutrient intakes in the Netherlands.

Energy and nutrient intake increased by 47-67% when amylase was added to fortified blended foods-a study among 12- to 35-month-old Burkinabe children.

Adding amylase to fortified blended foods can improve energy density, and increase child's energy and nutrient intake. The efficacy of this strategy is unknown for the World Food Programme's Super Cereal Plus (SC+) and Super Cereal (SC) blends. The primary goal of this study was to investigate the increased energy intake from amylase-containing SC+ and SC compared to control porridges in Burkinabe children. Secondly, energy intake from amylase-containing porridges compared to CERELAC® , Vitazom, and eeZeeBAR™ was studied. Thirdly, caregivers' (n = 100) porridge acceptability was investigated. The design was a randomized double-blind controlled cross-over trial studying the effect of amylase addition to SC+ and SC flours on porridge energy and nutrient intake in healthy Burkinabe children aged 12-23 (n = 80) and 24-35 months (n = 40). Amylase added to porridges increased energy density from 0.68 to 1.16 kcal/g for SC+ and from 0.66 to 1.03 kcal/g for SC porridges. Among children aged 12-23 months, mean energy intake from all porridges with amylase (135-164 kcal/meal) was significantly higher compared to control SC+ porridges (84-98 kcal/meal; model-based average). Among children aged 24-35 months, mean energy intakes were also significantly higher from all porridges with amylase added (245-288 kcal/meal) compared to control SC porridges (175-183 kcal/meal). Acceptability of the porridges among caregivers was rated neutral to good, both for amylase-added and non-amylase-containing porridges. These findings suggest that, among 12-35-month-old, adding amylase to fortified blended foods significantly increased energy and consequently nutrient intake per meal by 67% for SC+ and 47% for SC. Moreover, amylase-containing porridges were well accepted by the caregivers.

Maximizing the benefits and minimizing the risks of intervention programs to address micronutrient malnutrition: symposium report.

Interventions to address micronutrient deficiencies have large potential to reduce the related disease and economic burden. However, the potential risks of excessive micronutrient intakes are often not well determined. During the Global Summit on Food Fortification, 9-11 September 2015, in Arusha, a symposium was organized on micronutrient risk-benefit assessments. Using case studies on folic acid, iodine and vitamin A, the presenters discussed how to maximize the benefits and minimize the risks of intervention programs to address micronutrient malnutrition. Pre-implementation assessment of dietary intake, and/or biomarkers of micronutrient exposure, status and morbidity/mortality is critical in identifying the population segments at risk of inadequate and excessive intake. Dietary intake models allow to predict the effect of micronutrient interventions and their combinations, e.g. fortified food and supplements, on the proportion of the population with intakes below adequate and above safe thresholds. Continuous monitoring of micronutrient intake and biomarkers is critical to identify whether the target population is actually reached, whether subgroups receive excessive amounts, and inform program adjustments. However, the relation between regular high intake and adverse health consequences is neither well understood for many micronutrients, nor do biomarkers exist that can detect them. More accurate and reliable biomarkers predictive of micronutrient exposure, status and function are needed to ensure effective and safe intake ranges for vulnerable population groups such as young children and pregnant women. Modelling tools that integrate information on program coverage, dietary intake distribution and biomarkers will further enable program makers to design effective, efficient and safe programs.

Comparing Nutrient Profiles of Meat and Fish with Plant-Based Alternatives: Analysis of Nutrients, Ingredients, and Fortification Patterns.

Nutrient quality of plant-based meat and fish alternative (MFA) products has been reported as variable. The present objective was to compare the nutrient density of raw meat and fish with MFA products and to examine MFA ingredients and fortification patterns. Nutrient composition data for raw beef, pork, and chicken (n = 450) came from the USDA Standard Reference Legacy Reselase (SR28) nutrient composition database (n = 450). Data for plant-based meat alternatives (n = 118) came from the USDA Branded Food Products Database (BFPDB). Data for fish and seafood (n = 68) and alternatives (n = 12) came from the Danish Frida Database and Mintel (n = 503). Analyses compared macronutrient content and selected micronutrients per 100 g and percentage of US Daily Values. Nutrient density scores were based on the NRF5.3 algorithm. NRF5.3 scores were significantly lower for MFA products as compared to meat or fish. Saturated fat content was lower, but the mean MFA sodium content was 660 mg/100 g compared to 60 mg/100 g for beef. Mean protein content (17 g) was lower than for beef and pork (20 g). A search of ingredient lists found that fortification with most nutrients associated with animal source proteins (such as B vitamins, vitamin D, iodine, zinc, and omega-3 EPA and DHA) was minimal. Plant-based MFA products would benefit from nutrient standards and fortification guidelines to ensure that these products are not nutritionally inferior to the originals.

Plasma oxylipin profiling identifies polyunsaturated vicinal diols as responsive to arachidonic acid and docosahexaenoic acid intake in growing piglets.

The dose-responsiveness of plasma oxylipins to incremental dietary intake of arachidonic acid (20:4n-6; ARA) and docosahexaenoic acid (22:6n-3; DHA) was determined in piglets. Piglets randomly received one of six formulas (n = 8 per group) from days 3 to 27 postnatally. Diets contained incremental ARA or incremental DHA levels as follows (% fatty acid, ARA/DHA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D1) 0.66/0.33; and (D2) 0.67/0.62, resulting in incremental intake (g/kg BW/day) of ARA: 0.07 ± 0.01, 0.43 ± 0.03, 0.55 ± 0.03, and 0.82 ± 0.05 at constant DHA intake (0.82 ± 0.05), or incremental intake of DHA: 0.27 ± 0.02, 0.49 ± 0.03, and 0.81 ± 0.05 at constant ARA intake (0.54 ± 0.04). Plasma oxylipin concentrations and free plasma PUFA levels were determined at day 28 using LC-MS/MS. Incremental dietary ARA intake dose-dependently increased plasma ARA levels. In parallel, ARA intake dose-dependently increased ARA-derived diols 5,6- and 14,15-dihydroxyeicosatrienoic acid (DiHETrE) and linoleic acid-derived 12,13-dihydroxyoctadecenoic acid (DiHOME), downstream metabolites of cytochrome P450 expoxygenase (CYP). The ARA epoxide products from CYP are important in vascular homeostatic maintenance. Incremental DHA intake increased plasma DHA and most markedly raised the eicosapentaenoic acid (EPA) metabolite 17,18-dihydroxyeicosatetraenoic acid (DiHETE) and the DHA metabolite 19,20-dihydroxydocosapentaenoic acid (DiHDPE). In conclusion, increasing ARA and DHA intake dose-dependently influenced endogenous n-6 and n-3 oxylipin plasma concentrations in growing piglets, although the biological relevance of these findings remains to be determined.

The Potential of Food Fortification as an Enabler of More Environmentally Sustainable, Nutritionally Adequate Diets.

Policies encouraging shifts towards more plant-based diets can lead to shortfalls in micronutrients typically present in animal products (B-vitamins, vitamin D, calcium, iodine, iron, selenium, zinc, and long-chain omega-3 fatty acids). We modelled the effect of fortifying foods with these critical micronutrients, with the aim of achieving nutrition and sustainability goals, using food consumption data from Dutch adults (19-30 years). Three dietary scenarios were optimized for nutritional adequacy and 2030 greenhouse gas emissions (GHGE-2030) targets, respectively, with the fewest deviations from the baseline diet: (i) the current diet (mainly vitamin A- and D-fortified margarine, iodized bread, and some calcium- and vitamin D-fortified dairy alternatives and iron- and vitamin B12-fortified meat alternatives); (ii) all plant-based alternatives fortified with critical micronutrients; and (iii) fortified bread and oils. Optimizing the current diet for nutrition and GHGE-2030 targets reduced animal-to-plant protein ratios from ~65:35, to 33:67 (women) and 20:80 (men), but required major increases in legumes and plant-based alternatives. When fortifying all plant-based alternatives and, subsequently, bread and oil, smaller dietary changes were needed to achieve nutrition and GHGE-2030 targets. Fortifying food products with critical micronutrients, ideally with complementary education on plant-based foods, can facilitate the transition to healthier and more sustainable diets.

Implementing micronutrient fortification programs as a potential practical contribution to achieving sustainable diets.

Due to sustainability concerns related to current diets and environmental challenges, it is crucial to have sound policies to protect human and planetary health. It is proposed that sustainable diets will improve public health and food security and decrease the food system's effect on the environment. Micronutrient deficiencies are a well-known major public health concern. One-third to half of the world's population suffers from nutrient deficiencies, which have a negative impact on society in terms of unrealised potential and lost economic productivity. Large-scale fortification with different micronutrients has been found to be a useful strategy to improve public health. As a cost-effective strategy to improve micronutrient deficiency, this review explores the role of micronutrient fortification programmes in ensuring the nutritional quality (and affordability) of diets that are adjusted to help ensure environmental sustainability in the face of climate change, for example by replacing some animal-sourced foods with nutrient-dense, plant-sourced foods fortified with the micronutrients commonly supplied by animal-sourced foods. Additionally, micronutrient fortification considers food preferences based on the dimensions of a culturally sustainable diet. Thus, we conclude that investing in micronutrient fortification could play a significant role in preventing and controlling micronutrient deficiencies, improving diets and being environmentally, culturally and economically sustainable.

Modelling health and economic impact of nutrition interventions: a systematic review.

Diet related non-communicable diseases (NCDs), as well as micronutrient deficiencies, are of widespread and growing importance to public health. Authorities are developing programs to improve nutrient intakes via foods. To estimate the potential health and economic impact of these programs there is a wide variety of models. The aim of this review is to evaluate existing models to estimate the health and/or economic impact of nutrition interventions with a focus on reducing salt and sugar intake and increasing vitamin D, iron, and folate/folic acid intake. The protocol of this systematic review has been registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42016050873). The final search was conducted on PubMed and Scopus electronic databases and search strings were developed for salt/sodium, sugar, vitamin D, iron, and folic acid intake. Predefined criteria related to scientific quality, applicability, and funding/interest were used to evaluate the publications. In total 122 publications were included for a critical appraisal: 45 for salt/sodium, 61 for sugar, 4 for vitamin D, 9 for folic acid, and 3 for iron. The complexity of modelling the health and economic impact of nutrition interventions is dependent on the purpose and data availability. Although most of the models have the potential to provide projections of future impact, the methodological challenges are considerable. There is a substantial need for more guidance and standardization for future modelling, to compare results of different studies and draw conclusions about the health and economic impact of nutrition interventions.

Contribution of base diet, voluntary fortified foods and supplements to micronutrient intakes in the UK.

The objective of the present study was to evaluate the contribution of voluntary fortified foods and supplements to reducing micronutrient shortfalls in the UK population. A secondary analysis of the UK National Diet and Nutrition Survey was conducted (2012/13-2013/14, N 2546, 1·5-95 years). Micronutrient intakes were derived from food consumption intake data and food composition data and calculated as the proportion below or above the Dietary Reference Values for males and females of different age groups, for those on a base diet only, users of fortified foods but no supplements and users of fortified foods and supplements. Of the population consuming a base diet only, 21-45 % and 5-29 % fell below the Estimated Average Requirement (EAR) for minerals and vitamins, respectively. About 3-13 % fewer consumers of fortified foods fell below the EAR for vitamins and minerals. Supplements barely reduced the prevalence of intakes below the EAR. Among supplement non-users and users, 99 and 96 % failed to meet the reference intakes for vitamin D. More women than men were at risk of inadequacies of micronutrient intakes. The prevalence of inadequacies declined with increasing age. Voluntary fortified foods but not supplements made a meaningful contribution to intakes of vitamin and minerals, without risk of unacceptably high intakes. These insights may help the UK to define approaches to address micronutrients of concern in vulnerable groups.

Adequate Vitamin D Intake Cannot Be Achieved within Carbon Emission Limits Unless Food Is Fortified: A Simulation Study.

This study applied linear programming using a Dutch "model diet" to simulate the dietary shifts needed in order to optimize the intake of vitamin D and to minimize the carbon footprint, considering the popularity of the diet. Scenarios were modelled without and with additional fortified bread, milk, and oil as options in the diets. The baseline diet provided about one fifth of the adequate intake of vitamin D from natural food sources and voluntary vitamin D-fortified foods. Nevertheless, when optimizing this diet for vitamin D, these food sources together were insufficient to meet the adequate intake required, unless the carbon emission and calorie intake were increased almost 3-fold and 2-fold, respectively. When vitamin D-fortified bread, milk, and oil were added as options to the diet, along with increases in fish consumption, and decreases in sugar, snack, and cake consumption, adequate intakes for vitamin D and other nutrients could be met within the 2000 kcal limits, along with a relatively unchanged carbon footprint. Achieving vitamin D goals while reducing the carbon footprint by 10% was only possible when compromising on the popularity of the diet. Adding vitamin D to foods did not contribute to the total carbon emissions. The modelling study shows that it is impossible to obtain adequate vitamin D through realistic dietary shifts alone, unless more vitamin D-fortified foods are a necessary part of the diet.

Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study.

An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.

Prenatal arachidonic acid exposure and selected immune-related variables in childhood.

Arachidonic acid (AA) is considered essential in fetal development and some of its metabolites are thought to be important mediators of the immune responses. Therefore, we studied whether prenatal exposure to AA is associated with some immune-related clinical conditions and plasma markers in childhood. In 280 children aged 7 years, atopy, lung function and plasma inflammation markers were measured and their relationships with early AA exposure were studied by linear and logistic regression analyses. AA exposure was deduced from AA concentrations in plasma phospholipids of the mothers collected at several time points during pregnancy and at delivery, and in umbilical cord plasma and arterial and venous wall phospholipids. In unadjusted regression analyses, significant positive associations were observed between maternal AA concentrations at 16 and 32 weeks of pregnancy (proxies for fetal AA exposure) and peak expiratory flow decline after maximal physical exercise and plasma fibrinogen concentrations of their children, respectively. However, after correction for relevant covariables, only trends remained. A significant negative relationship was observed between AA concentrations in cord plasma (reflecting prenatal AA exposure) and the average daily amplitude of peak expiratory flow at rest, which lost significance after appropriate adjustment. Because of these few, weak and inconsistent relationships, a major impact of early-life exposure to AA on atopy, lung function and selected plasma inflammation markers of children at 7 years of age seems unlikely.

Lactose-Free Dairy Products: Market Developments, Production, Nutrition and Health Benefits.

Lactose-free dairy is able to provide the essential nutrients present in regular dairy products, like calcium and vitamins, to those that are not able to digest lactose. This product category currently has a wide and growing health appeal to consumers. In recent years, the quality and product variety in the lactose-free dairy segment has been increasing significantly, giving consumers more tempting products to decide from. As a result, lactose-free dairy is now the fastest growing market in the dairy industry. This review discusses the market developments and production possibilities and issues related to the wide variation of lactose-free dairy products that are currently available. Additionally, the health benefits that lactose-free dairy may offer compared to dairy avoidance are illustrated.

The Role of Nutrients in Reducing the Risk for Noncommunicable Diseases during Aging.

An increasing aging population worldwide accounts for a growing share of noncommunicable diseases (NCDs) of the overall social and economic burden. Dietary and nutritional approaches are of paramount importance in the management of NCDs. As a result, nutrition programs are increasingly integrated into public health policies. At present, programs aimed at reducing the burden of NCDs have focused mostly on the excess of unhealthy nutrient intakes whereas the importance of optimizing adequate essential and semi-essential nutrient intakes and nutrient-rich diets has received less attention. Surveys indicate that nutrient intakes of the aging population are insufficient to optimally support healthy aging. Vitamin and mineral deficiencies in older adults are related to increased risk of NCDs including fatigue, cardiovascular disease, and cognitive and neuromuscular function impairments. Reviewed literature demonstrates that improving intake for certain nutrients may be important in reducing progress of NCDs such as musculoskeletal disorders, dementia, loss of vision, and cardiometabolic diseases during aging. Current knowledge concerning improving individual nutrient intakes to reduce progression of chronic disease is still emerging with varying effect sizes and levels of evidence. Most pronounced benefits of nutrients were found in participants who had low nutrient intake or status at baseline or who had increased genetic and metabolic needs for that nutrient. Authorities should implement ways to optimize essential nutrient intake as an integral part of their strategies to address NCDs.

Effect of small-quantity lipid-based nutrient supplements on growth, psychomotor development, iron status, and morbidity among 6- to 12-mo-old infants in South Africa: a randomized controlled trial.

Background: Evidence on the effect of small-quantity lipid-based nutrient supplements (SQ-LNSs) on early child growth and development is mixed. Objective: This study assessed the effect of daily consumption of 2 different SQ-LNS formulations on linear growth (primary outcome), psychomotor development, iron status (secondary outcomes), and morbidity in infants from age 6 to 12 mo within the context of a maize-based complementary diet. Methods: Infants (n = 750) were randomly assigned to receive SQ-LNS, SQ-LNS-plus, or no supplement. Both SQ-LNS products contained micronutrients and essential fatty acids. SQ-LNS-plus contained, in addition, docosahexaenoic acid, arachidonic acid (important for brain and eye development), lysine (limiting amino acid in maize), phytase (enhances iron absorption), and other nutrients. Infants' weight and length were measured bimonthly. At age 6 and 12 mo, psychomotor development using the Kilifi Developmental Inventory and South African Parent Rating Scale and hemoglobin, plasma ferritin, C-reactive protein, and α1-acid glycoprotein were assessed. WHO Motor Milestone outcomes, adherence, and morbidity were monitored weekly through home visits. Primary analysis was by intention-to-treat, comparing each SQ-LNS group with the control. Results: SQ-LNS-plus had a positive effect on length-for-age zscore at age 8 mo (mean difference: 0.11; 95% CI: 0.01, 0.22; P = 0.032) and 10 mo (0.16; 95% CI: 0.04, 0.27; P = 0.008) but not at 12 mo (0.09; 95% CI: -0.02, 0.21; P = 0.115), locomotor development score (2.05; 95% CI: 0.72, 3.38; P = 0.003), and Parent Rating Score (1.10; 95% CI: 0.14, 2.07; P = 0.025), but no effect for weight-for-age zscore. Both SQ-LNS (P = 0.027) and SQ-LNS-plus (P = 0.005) improved hemoglobin concentration and reduced the risk of anemia, iron deficiency, and iron-deficiency anemia. Both SQ-LNS products reduced longitudinal prevalence of fever, coughing, and wheezing but increased incidence and longitudinal prevalence of diarrhea, vomiting, and rash/sores. Conclusions: Point-of-use fortification with SQ-LNS-plus showed an early transient effect on linear growth and improved locomotor development. Both SQ-LNS products had positive impacts on anemia and iron status. This trial was registered at clinicaltrials.gov as NCT01845610.

Dietary arachidonic acid dose-dependently increases the arachidonic acid concentration in human milk.

Lactation hampers normalization of the maternal arachidonic acid (AA) status, which is reduced after pregnancy and can further decline by the presently recommended increased consumption of (n-3) long-chain PUFA [(n-3) LCPUFA]. This may be unfavorable for breast-fed infants, because they also require an optimum supply of (n-6) LCPUFA. We therefore investigated the LCPUFA responses in nursing mothers upon increased consumption of AA and (n-3) LCPUFA. In a parallel, double-blind, controlled trial, lactating women received for 8 wk no extra LCPUFA (control group, n = 8), 200 (low AA group, n = 9), or 400 (high AA group, n = 8) mg/d AA in combination with (n-3) LCPUFA [320 mg/d docosahexaenoic acid (DHA), 80 mg/d eicosapentaenoic acid, and 80 mg/d other (n-3) fatty acids], or this dose of (n-3) LCPUFA alone [DHA + eicosapentaenoic acid group, n = 8]. Relative concentrations of AA, DHA, and sums of (n-6) and (n-3) LCPUFA were measured in milk total lipids (TL) and erythrocyte phospholipids (PL) after 2 and 8 wk and changes were compared by ANCOVA. The combined consumption of AA and (n-3) LCPUFA caused dose-dependent elevations of AA and total (n-6) LCPUFA concentrations in milk TL and did not significantly affect the DHA and total (n-3) LCPUFA increases caused by (n-3) LCPUFA supplementation only. This latter treatment did not significantly affect breast milk AA and total (n-6) LCPUFA concentrations. AA and DHA concentrations in milk TL and their changes were strongly and positively correlated with their corresponding values in erythrocyte PL (r(2) = 0.27-0.50; P

Considerations for Secondary Prevention of Nutritional Deficiencies in High-Risk Groups in High-Income Countries.

Surveys in high-income countries show that inadequacies and deficiencies can be common for some nutrients, particularly in vulnerable subgroups of the population. Inadequate intakes, high requirements for rapid growth and development, or age- or disease-related impairments in nutrient intake, digestion, absorption, or increased nutrient losses can lead to micronutrient deficiencies. The consequent subclinical conditions are difficult to recognize if not screened for and often go unnoticed. Nutrient deficiencies can be persistent despite primary nutrition interventions that are aimed at improving dietary intakes. Secondary prevention that targets groups at high risk of inadequacy or deficiency, such as in the primary care setting, can be a useful complementary approach to address persistent nutritional gaps. However, this strategy is often underestimated and overlooked as potentially cost-effective means to prevent future health care costs and to improve the health and quality of life of individuals. In this paper, the authors discuss key appraisal criteria to consider when evaluating the benefits and disadvantages of a secondary prevention of nutrient deficiencies through screening.

Effect of oral protein hydrolysate on glucose control in patients with gestational diabetes.

BACKGROUND & AIMS: In type 2 diabetic patients, a casein-based protein hydrolysate has been shown to increase plasma insulin and to lower plasma glucose. In the present study, we examined the acute and prolonged effects of protein hydrolysate on postprandial glucose, insulin and C-peptide responses after a standardised breakfast and the effect on daily glucose control in patients with gestational diabetes. METHODS: In a single-centre randomised double blind placebo controlled design, patients with mild gestational diabetes (no use of insulin or oral antidiabetic agents; n = 26/group) were allocated to receive a protein hydrolysate drink, 8.5 g before breakfast and 8.5 g before dinner or a placebo drink which was identical to the protein hydrolysate drink in appearance and taste, yet lacked carbohydrate, fat or protein, for 8 days. RESULTS: Baseline characteristics including fasting levels of glucose, insulin, C-peptide and insulin-glucose ratio were similar between the groups. Compared to the placebo drink, neither the first dose of the protein hydrolysate drink nor the final dose had effects on 4-h area under the curve for plasma levels of insulin and C-peptide, or the insulin-to-glucose ratio; however, plasma glucose was moderately lower between t = 45, 60 and 75 min. In addition, mean daily capillary glucose levels were lower in the protein hydrolysate group. Two patients in the PH drink group had to be withdrawn because of vomiting after the first dose. CONCLUSIONS: In patients with gestational diabetes, a twice-daily dose of 8.5 g of protein hydrolysate of casein had no insulinotropic effects, but did moderately reduce plasma glucose levels, suggesting an increase in insulin sensitivity.

Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting.

The Aspergillus niger-derived prolyl endoprotease (AN-PEP) has previously been shown to degrade gluten in healthy subjects when added to an intragastrically infused meal. The current study investigated the efficacy of AN-PEP in a physiological meal setting. In this randomized placebo-controlled crossover study, 18 gluten-sensitive subjects consumed a porridge containing 0.5 g gluten together with two tablets either containing a high or low dose of AN-PEP, or placebo. Gastric and duodenal content was sampled over 180 minutes, and areas under the curve of gluten concentrations were calculated. The primary outcome, i.e. success rate of high dose AN-PEP defined as at least 50% gluten degradation compared to placebo in the duodenum, was achieved in 10 of 13 comparisons. In the stomach, gluten levels were reduced from 176.9 (median, interquartile range 73.5-357.8) to 22.0 (10.6-50.8, p = 0.001) in the high dose and to 25.4 µg × min/ml (16.4-43.7, p = 0.001) in the low dose. In the duodenum, gluten levels were reduced from 14.1 (8.3-124.7) in the placebo to 6.3 (3.5-19.8, p = 0.019) in the high dose and to 7.4 µg × min/ml in the low dose (3.8-12.0, p = 0.015). Thus even in a physiological meal setting, AN-PEP significantly degraded most gluten in the stomach before it entered the duodenum.