Effects of liraglutide on gallbladder emptying: A randomized, placebo-controlled trial in adults with overweight or obesity.

AIMS: Treatment with liraglutide 3.0 mg has been associated with gallbladder-related adverse events. To conduct a single-centre, double-blind, 12-week trial comparing the effect of 0.6 mg liraglutide and steady-state liraglutide 3.0 mg with placebo on gallbladder emptying in adults with body mass index (BMI) ≥27 kg/m2 and without diabetes. METHODS: Participants were randomized 1:1 to once-daily subcutaneous liraglutide (n = 26) or placebo (n = 26), starting at 0.6 mg with 0.6-mg weekly increments to 3.0 mg, with nutritional and physical activity counselling. A 600-kcal (23.7 g fat) liquid meal test was performed at baseline, after the first dose and after 12 weeks. The primary endpoint was the 12-week maximum postprandial gallbladder ejection fraction (GBEFmax ), measured over 240 minutes after starting the meal. RESULTS: Baseline characteristics were similar between groups (mean ± SD overall age 47.6 ± 10.0 years, BMI 32.6 ±3.4 kg/m2 , 50% women). Mean 12-week GBEFmax (treatment difference -3.7%, 95% confidence interval [CI] -13.1, 5.7) and area under the GBEF curve in the first 60 minutes (-390% × min, 95% CI -919, 140) did not differ for liraglutide 3.0 mg (n = 23) vs placebo (n = 24). The median (range) time to GBEFmax was 151 (11-240) minutes with liraglutide 3.0 mg and 77 (22-212) minutes with placebo. Similar findings were noted after the first 0.6-mg liraglutide dose. Gastrointestinal disorders, notably nausea and constipation, were the most frequently reported adverse events. CONCLUSIONS: Treatment with liraglutide did not affect the GBEFmax but appeared to prolong the time to GBEFmax .

Quinine sensitivity influences the acceptance of sea-buckthorn and grapefruit juices in 9- to 11-year-old children.

The acceptance of novel foods by children is related to a number of factors, and differences in taste sensitivity may form some specific challenges. High sensitivity might be a barrier to the acceptance of sour/bitter products by children. This study investigated the effect of sensitivity to bitter, sour, sweet, and salty tastes on the acceptance of Nordic juices in 9- to 11-year-old children. A total of 328 children were subjected to two taste sensitivity tests for quinine, citric acid, sucrose, and NaCl. Their acceptance of six juices (carrot, rosehip, sea-buckthorn, lingonberry, grapefruit, and aronia) was measured. Bitter sensitivity was found to be significantly correlated to the intake of the sweet sea-buckthorn and lingonberry juices; the most bitter-sensitive children exhibited the highest intake of these juices. The opposite relationship was found for bitter sensitivity and the intake of the bitter grapefruit juice. Sour, sweet, and salt sensitivities did not affect the intake of any of the juices. Liking scores were not affected by sensitivity. In conclusion, bitter sensitivity appears to influence food intake in children to a greater extent than sour, sweet, or salt sensitivity. Bitter-sensitive children exhibited a reduced intake of grapefruit juice and a higher intake of sucrose-sweetened juices. Thus, bitter sensitivity might be a challenge in the acceptance of certain bitter foods.

Eating a rainbow. Introducing vegetables in the first years of life in 3 European countries.

Low vegetable consumption in children is a concern in many EU countries, fewer than one fifth of children in Europe consume the WHO recommended amounts. Systematic studies demonstrate that experience with a variety of vegetables early in childhood can promote later consumption as early dietary habits often track into adulthood. This study examined pre-school children's experience with vegetables across three European countries in order to assess cultural differences, effects of age and culinary practices. Mothers of pre-school children (N=234) in the UK (N=71), Denmark (N=93) and France (N=70) completed a survey assessing parental and infant familiarity, frequency of offering and liking for 56 vegetables as well as preparation techniques for these vegetables. Analyses revealed that although children aged 25-36 months had been introduced to the greatest number of vegetables, children aged 6-12 months were offered vegetables more frequently and had a higher reported liking for these vegetables. UK children's liking was related to frequency of maternal intake and frequency of offering. Denmark had introduced the greatest number of vegetables and offered vegetables more frequently than both the UK and France. Choice of preparation methods differed between countries while choice of seasonings was similar. Results suggest increasing variety and frequency of vegetable offering between 6 and 12 months, when children are most receptive, may promote vegetable consumption in children.

Mere exposure and flavour-flavour learning increase 2-3 year-old children's acceptance of a novel vegetable.

Vegetable consumption is low among many children. This study compared the efficacy of the exposure learning strategies mere exposure, flavour-flavour and flavour-nutrient learning in changing children's intake of a novel vegetable. An unmodified artichoke purée was served at pre-testing. Hereafter children were exposed 10 times to unmodified purée (mere exposure, n=32), a sweetened purée (flavour-flavour learning, n=33) or an energy dense purée with added fat (flavour-nutrient learning, n=39). Unmodified and sweet purée contained approximately 200 kJ/100g; the energy dense purée 580 kJ/100g. The unmodified purée was served again at post-testing, 3 and 6 months after last exposure to monitor long-term effects of learning. Intake of purée increased in the mere exposure and flavour-flavour condition, and was unchanged in the flavour-nutrient condition. Mere exposure changed children's intake by the 5th exposure, flavour-flavour learning by the 10th. Mere exposure led to the largest increase in intake of unmodified purée at post-test and over 6 months. Children following flavour-flavour learning consumed more of the sweet purée than of unmodified purée. About 30-40% of the children were resistant to acceptance changes. The results of this study imply that mere exposure and flavour-flavour learning are powerful strategies for changing children's acceptance of a novel vegetable, even though a substantial number of children are resistant to these types of exposure learning.

Optimising Repeated Exposure: Determining Optimal Stimulus Shape for Introducing a Novel Vegetable among Children.

Although it is well evident that a healthy diet rich in fruit and vegetables could prevent a number of major chronic diseases, national and international guidelines concerning their intake are not being reached by a large percentage of the population, including children. Thus, it is of interest to investigate how the consumption of this food group by children could be increased. The aim of this study was to examine the impact of serving style on the consumption of a raw snack vegetable (daikon) and the influence of its exposure on liking and intake of the vegetable. A group of 185 children 3-5 years old participated in the study. Two kindergartens served as intervention groups, while the third was assigned to be the control group of the study (n = 50). The intervention groups were repeatedly exposed to one of three different serving styles of daikon: sticks (n = 42), triangles (n = 46) or grated (n = 47), and they were all visited 7 times during the exposure period, on the same frequency (twice per week). Familiarity and liking of the target vegetable, daikon, and six other vegetables (cucumber, celery, celeriac, broccoli, cauliflower and beetroot) were measured at baseline, post-intervention and two follow up sessions (3- and 6-month) to investigate the likelihood of generalisation effects. Intake of daikon was measured at all control sessions and exposures. Moreover, children were asked to rank their favourite serving style of daikon and beetroot, among triangle, stick and grated, towards understanding the influence of shape on the efficacy of the exposure. The results revealed significant changes between liking and intake of daikon for the groups of triangles and sticks and the control group (p < 0.05). The group that received grated daikon did not show significant differences in liking and at intake levels during the exposures but performed well in the long-term. Throughout the exposure period, intake levels followed an overall increasing pattern, with all the groups to demonstrate a decrease of their intake at the last session, which was not found significant for the triangle group. Mere exposure was efficient towards increasing liking and intake of the novel vegetable with all the shapes to deliver positive results, but based on this study no particular serving style can be recommended.

Optimising Repeated Exposure: Determining Optimal Exposure Frequency for Introducing a Novel Vegetable among Children.

Fruit and vegetables are important components of a healthy diet, but unfortunately many children are not consuming enough to meet the recommendations. Therefore, it is crucial to develop strategies towards increasing the acceptance of this food group. This study aims to investigate the effect of different repeated exposure frequencies on fruit and vegetable acceptance using a novel vegetable, daikon, among 3-6-year-old children. One hundred and fifty-nine children participated in this study. Eight kindergarten teams were assigned to one of the following groups: Three different intervention groups with varying exposure frequencies, but all receiving seven exposures: Twice a week (n = 47), once a week (n = 32) and once every second week (n = 30), and a control group (n = 50). Liking and familiarity of daikon and other vegetables (cucumber, celery, celeriac, broccoli, cauliflower and beetroot) were assessed at baseline, post-intervention and two follow up sessions (3 and 6 months) to test for potential generalisation effects and observe the longevity of the obtained effects. Intake of daikon was measured at all exposures and test sessions. Results showed significant increases (p ≤ 0.05) in liking and intake of daikon for all three frequencies and the control group. Over the exposures, intake of daikon increased until the 4th exposure for all the groups, where a plateau was reached. No systematic generalisation effects were found. Repeated exposure was a successful approach to increase liking and intake of a novel vegetable with all exposure frequencies to be effective, and no particular exposure frequency can be recommended. Even the few exposures the control group received were found to be sufficient to improve intake and liking over 6 months (p ≤ 0.05), indicating that exposures to low quantities of an unfamiliar vegetable may be sufficient.

Differential transfer of dietary flavour compounds into human breast milk.

Transfer of dietary flavour compounds into human milk is believed to constitute the infant's early flavour experiences. This study reports on the time-dependent transfer of flavour compounds from the mother's diet to her breast milk using a within-subject design. Eighteen lactating mothers completed three test days on which they provided a baseline milk sample prior to ingestion of capsules containing 100 mg d-carvone, l-menthol, 3-methylbutyl acetate and trans-anethole. Milk samples were collected 2, 4, 6 and 8 h post-ingestion and analysed by a dynamic headspace method and gas chromatography-mass spectroscopy. The recovery quantities were adjusted for variations in milk fat content. Concentration-time profiles for d-carvone and trans-anethole revealed a maximum around 2 h post-ingestion, whereas the profile for l-menthol showed a plateau pattern. The ester 3-methylbutyl acetate could not be detected in the milk, but a single determination showed traces (<0.4 ppb) in a 1 h milk collection. Flavour compounds appeared to be transmitted differentially from the mother's diet to her milk. The results imply that human milk provides a reservoir for time-dependent chemosensory experiences to the infant; however, volatiles from the diet are transferred selectively and in relatively low amounts.

Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects.

BACKGROUND AND OBJECTIVE: Semaglutide is a glucagon-like peptide-1 analogue in development for the once-weekly treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (metformin, warfarin, atorvastatin and digoxin) was evaluated in healthy subjects. METHODS: Subjects received metformin (500 mg twice daily for 3.5 days), warfarin (25 mg, single dose), atorvastatin (40 mg, single dose) or digoxin (0.5 mg, single dose) before and with subcutaneous semaglutide treatment at steady state (1.0 mg). Lack of drug-drug interaction was concluded if the 90% confidence intervals for the area under the plasma concentration-time curve ratio before and with semaglutide were within a pre-specified interval (0.80-1.25). RESULTS: Overall, metformin, warfarin, atorvastatin and digoxin pharmacokinetics were not affected to a clinically relevant degree with semaglutide co-administration. Estimated area under the plasma concentration-time curve ratios for all concomitant medications before and with semaglutide treatment were within the pre-specified interval. In addition, semaglutide did not affect maximum plasma concentration of concomitant medications to a relevant degree. Furthermore, no clinically relevant change in international normalised ratio response to warfarin was observed with semaglutide co-administration. Most adverse events with semaglutide treatment were mild or moderate. Adverse events with semaglutide and co-administered medication were comparable to those reported during treatment with semaglutide alone, and were mostly gastrointestinal related. CONCLUSIONS: No clinically significant pharmacokinetic or pharmacodynamic interactions were identified and no new safety issues observed with combined treatment with semaglutide. This suggests that no dose adjustments should be required when semaglutide is administered concomitantly with these medications.

Learning to eat vegetables in early life: the role of timing, age and individual eating traits.

Vegetable intake is generally low among children, who appear to be especially fussy during the pre-school years. Repeated exposure is known to enhance intake of a novel vegetable in early life but individual differences in response to familiarisation have emerged from recent studies. In order to understand the factors which predict different responses to repeated exposure, data from the same experiment conducted in three groups of children from three countries (n = 332) aged 4-38 m (18.9±9.9 m) were combined and modelled. During the intervention period each child was given between 5 and 10 exposures to a novel vegetable (artichoke puree) in one of three versions (basic, sweet or added energy). Intake of basic artichoke puree was measured both before and after the exposure period. Overall, younger children consumed more artichoke than older children. Four distinct patterns of eating behaviour during the exposure period were defined. Most children were "learners" (40%) who increased intake over time. 21% consumed more than 75% of what was offered each time and were labelled "plate-clearers". 16% were considered "non-eaters" eating less than 10 g by the 5th exposure and the remainder were classified as "others" (23%) since their pattern was highly variable. Age was a significant predictor of eating pattern, with older pre-school children more likely to be non-eaters. Plate-clearers had higher enjoyment of food and lower satiety responsiveness than non-eaters who scored highest on food fussiness. Children in the added energy condition showed the smallest change in intake over time, compared to those in the basic or sweetened artichoke condition. Clearly whilst repeated exposure familiarises children with a novel food, alternative strategies that focus on encouraging initial tastes of the target food might be needed for the fussier and older pre-school children.

Effects of repeated exposure on acceptance of initially disliked and liked Nordic snack bars in 9-11 year-old children.

BACKGROUND & AIMS: Children's food choices are guided by their preferences. It is established, however, that repeated exposure to a novel food increases children's acceptance. This study investigated how acceptance of an initially liked and disliked snack bar develops in 9-11 year-old children. METHODS: 315 children were randomised into three groups: A control group (n = 111) and two groups exposed to an initially liked kamut bar (n = 94) and an initially disliked sea buckthorn bar (n = 110). Acceptance of both bars was tested before and after the exposure period, and on the 9th exposure. RESULTS: Intake of both bars increased significantly in the exposure groups. There was no difference in the control groups' intake or liking of the bars between pre and post-testing. Liking rose significantly for children exposed to the disliked sea buckthorn bar, while this was not observed in children exposed to the liked kamut bar. In a post-test children exposed to kamut bars had higher intake of that bar than non-exposed children. This was also observed for the sea buckthorn bar that was also given significantly higher liking scores by the exposure group. CONCLUSIONS: The majority of children exposed to an initially disliked bar increase acceptance after nine exposures to the same level as an initially liked bar. Children repeatedly exposed to a liked bar show stable acceptance.

Acceptance of Nordic snack bars in children aged 8-11 years.

BACKGROUND: A health promoting diet is suggested to be tailored to regional circumstances to preserve the cultural diversity in eating habits, as well as contribute to more environmentally friendly eating. It may influence consumer acceptance, however, if the components of the diet differs considerably from their habitual food. OBJECTIVE: This study aimed to investigate whether snack bars composed of Nordic ingredients were accepted by 8-11 year-old Danish (n=134) and Swedish (n=109) children. DESIGN: A seven-point hedonic scale was used to measure the children's acceptance of five snack bars that varied in their composition of whole grains, berries and nuts. A preference rank ordering of the five bars was also performed. RESULTS: The results showed that samples that were rated highest in liking and were most preferred in both countries were a kamut/pumpkin bar and an oat/cranberry bar. The sample with the lowest rating that was also least preferred was a pumpernickel/sea buckthorn bar. Flavour was the most important determinant of overall liking followed by texture, odour and appearance. CONCLUSIONS: Children's acceptances and preferences were highly influenced by the sensory characteristics of the bars, mainly flavour. In agreement with earlier studies, the novel food ingredients seemed to influence children's preferences. The Nordic snack bars may have a potential to be a snack option for Danish and Swedish school children, but repeated exposures to the products are recommended to increase children's acceptance.

Breastfeeding facilitates acceptance of a novel dietary flavour compound.

BACKGROUND & AIMS: Infants may learn to accept flavours via exposure to flavour in mother's milk. This study examines whether acceptance of a flavour compound develops over 10 exposures through mother's milk (part 1), and how such acceptance evolves after 10 exposures, on alternate days, to the same flavour in solid food (part 2). METHODS: Three groups of 5-8 month-old infants participated. Breast-fed infants were randomised into two groups: a non-exposed group (n=20) and a group exposed to caraway flavour (d-carvone) via mother's milk (n=20). Mothers in the second group consumed a caraway-flavoured food. The third group was composed of formula-fed infants whose mothers consumed the caraway-flavoured food (n=8). Infants' acceptance of caraway-flavour was tested after both exposure periods by evaluating, on separate days, intake parameters and mother's judgement of liking of plain and caraway-flavoured purées. RESULTS: Part 1 showed that exposed and non-exposed breast-fed infants had higher initial acceptance of the caraway-flavoured purée than formula-fed infants. Part 2 results showed no evolution in acceptance of caraway-flavoured purée among breast-fed infants. In contrast formula-fed infants' acceptance of caraway-flavoured purée increased, corresponding to flavour-specific acceptance learning. CONCLUSIONS: This study suggests that breastfeeding facilitates acceptance of novel flavours. This effect is not necessarily due to exposure to specific flavour compounds.

A single measurement is inadequate to estimate enterolactone levels in danish postmenopausal women due to large intraindividual variation.

Single measurements of enterolactone (ENL) used in epidemiologic studies are influenced by intraindividual variation. The objective of this controlled study was to investigate short-term intraindividual variations in serum and urine ENL. Based on these variations, the number of samples required to describe the basal ENL level was estimated. Healthy Danish postmenopausal women (n = 6) aged 54-67 y completed 3 study periods of 24 h within 2 mo. Blood samples were collected at 0, 4, 6, 8, 12, and 24 h and 24-h urine samples were collected. A low-lignan, standardized diet of 3 meals was served. ENL was measured by time-resolved fluoroimmunoassay. Intraindividual and interindividual variations were estimated using a mixed model with repeated measurements. Significant and systematic intraindividual within-day variations (CV) of 31% were observed in serum. Intraindividual day-to-day variations were 56% and overall intraindividual variation of samples collected at random times and on different days was estimated to be 64%. Describing this overall variation required 7 blood samples when estimated with a precision of 50% and 95% confidence. Day-to-day variations in 24-h urine samples were 49%. Large within-day and day-to-day variations suggest that a single measurement of ENL is inadequate to estimate the basal ENL level.

Intake of whole grains and vegetables determines the plasma enterolactone concentration of Danish women.

The mammalian lignan enterolactone (ENL), which is produced from dietary plant-lignan precursors by the intestinal microflora, may protect against breast cancer and other hormone-dependent cancers. This cross-sectional study examined which variables related to diet and lifestyle were associated with high plasma concentrations of ENL in Danish postmenopausal women. Plasma ENL was measured by time-resolved fluoroimmunoassay in 857 Danish women aged 50-64 y who participated in a prospective cohort study. Diet was assessed using a semiquantitative FFQ, and background information on lifestyle was collected using a self-administered questionnaire. Multiple analyses of covariance were completed in two steps. The median plasma ENL concentration was 27 nmol/L (range 0-455 nmol/L). In covariance analyses, positive associations were found between consumption of cereals, vegetables, and beverages and plasma ENL concentration. When analyzing subgroups of these food groups, the associations were confined to whole-grain products, cabbage, leafy vegetables, and coffee. For fat and the nondietary variables, negative associations between BMI, smoking, and frequency of bowel movements and plasma ENL concentration were observed. These data show that foods high in ENL precursors are associated with high concentrations of ENL. Furthermore, smoking, frequent bowel movements, and consumption of fat seems to have a negative affect on the ENL concentration. In conclusion, whole grains and vegetables are the most important dietary providers of plant lignans for the concentration of ENL in Danish postmenopausal women, and if ENL is found to protect against cancer or heart disease, the intake of whole grains and vegetables should be increased.