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Background: Chronic kidney disease (CKD) is associated with an increased incidence of cardiovascular disease (CVD). The Anti-oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study showed that a multistep treatment strategy improved carotid intima-media thickness, endothelial function, and microalbuminuria in patients with stages 2 to 4 CKD. Increased plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been linked to greater CVD risk in patients with CKD. The aim of this study is to assess effects of the multistep intervention on plasma ADMA concentrations in the ATIC Study.Study Design: Secondary analysis of a randomized double-blind placebo-controlled trial.Setting& Participants: 93 patients with creatinine clearance of 15 to 70 mL/min/1.73 m(2) (according to the Cockcroft-Gault equation) from 7 outpatient clinics in Amsterdam, The Netherlands.Intervention: The treatment group received sequential treatment consisting of pravastatin, 40 mg/d. After 6 months, vitamin E, 300 mg/d, was added, and after another 6 months, homocysteine-lowering therapy (folic acid, 5 mg/d; pyridoxine, 100 mg/d; and vitamin B(12), 1 mg/d, all in 1 tablet) were added and continued for another year. The control group received matching placebos.Outcome& Measures: Plasma ADMA levels.Results: 36 participants (77%) in the treatment group and 38 (83%) in the placebo group completed the study. Mean ADMA and symmetric dimethylarginine concentrations in the total study population were 0.53 +/- 0.07 (SD) and 1.14 +/- 0.46 mumol/L, respectively. After 24 months, there was no overall effect of the treatment strategy on ADMA concentrations (beta = -0.006; P = 0.27). Analysis of separate treatment effects suggested that vitamin E significantly decreased ADMA levels by 4% in the treatment group compared with the placebo group (multiple adjusted P = 0.02).Limitations: The study was a secondary analysis, power calculation was based on the primary end point of carotid intima-media thickness, mean plasma ADMA levels were relatively low.Conclusion: Overall, a multistep treatment strategy consisting of pravastatin, vitamin E, and B vitamins had no effect on plasma ADMA levels in a stage 2 to 4 CKD population. This suggests that the beneficial effects of the intervention were not mediated by changes in ADMA levels. Possible ADMA-lowering effects of vitamin E deserve further attention. [ABSTRACT FROM AUTHOR]

BACKGROUND: A high plasma concentration of total homocysteine (tHcy) is associated with increased risk of cardiovascular disease. A high protein intake and hence a high intake of methionine-the sole dietary precursor of homocysteine-may raise plasma tHcy concentrations. OBJECTIVES: We studied whether high intake of protein increases plasma concentrations of tHcy in the fasting state and throughout the day. DESIGN: We conducted a randomized, dietary controlled, crossover trial in 20 healthy men aged 18-44 y. For 8 d, men consumed a controlled low-protein diet enriched with either a protein supplement [high-protein diet (21% of energy as protein)] or an isocaloric amount of short-chain glucose polymers [low-protein diet (9% of energy as protein)]. After a 13-d washout period, treatments were reversed. On days 1 and 8 of each treatment period, blood was sampled before breakfast (fasting) and throughout the day. RESULTS: Fasting tHcy concentrations did not differ significantly after the 1-wk high-protein and the 1-wk low-protein diets. The high-protein diet resulted in a significantly higher area under the 24-h homocysteine-by-time curves compared with the low-protein diet, both on day 1 (difference: 45.1 h x mumol/L; 95% CI: 35.3, 54.8 h x mumol/L; P < 0.0001) and on day 8 (difference: 24.7 h x mumol/L; 95% CI: 15.0, 34.5 h x mumol/L; P < 0.0001). CONCLUSIONS: A high-protein diet increases tHcy concentrations throughout the day but does not increase fasting tHcy concentrations. As previously shown, the extent of the tHcy increase is modified by the amino acid composition of the protein diet. The clinical relevance of this finding depends on whether high concentrations of tHcy-particularly postprandially-cause cardiovascular disease. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: A high homocysteine concentration is a potential risk factor for cardiovascular disease that can be reduced through betaine supplementation. Choline is the precursor for betaine, but the effects of choline supplementation on plasma total homocysteine (tHcy) concentrations in healthy humans are unknown. OBJECTIVE: The objective was to investigate whether supplementation with phosphatidylcholine, the form in which choline occurs in foods, reduces fasting and postmethionine-loading concentrations of plasma tHcy in healthy men with mildly elevated plasma tHcy concentrations. DESIGN: In a crossover study, 26 men ingested approximately 2.6 g choline/d (as phosphatidylcholine) or a placebo oil mixture for 2 wk in random order. Fatty acid composition and fat content were similar for both treatments. A methionine-loading test was performed on the first and last days of each supplementation period. RESULTS: Phosphatidylcholine supplementation for 2 wk decreased mean fasting plasma tHcy by 18% (-3.0 micromol/L; 95% CI: -3.9, -2.1 micromol/L). On the first day of supplementation, a single dose of phosphatidylcholine containing 1.5 g choline reduced the postmethionine-loading increase in tHcy by 15% (-4.8 micromol/L; 95% CI: -6.8, -2.8 micromol/L). Phosphatidylcholine supplementation for 2 wk reduced the postmethionine-loading increase in tHcy by 29% (-9.2 micromol/L; 95% CI: -11.3, -7.2 micromol/L). All changes were relative to placebo. CONCLUSIONS: A high daily dose of choline, supplemented as phosphatidylcholine, lowers fasting as well as postmethionine-loading plasma tHcy concentrations in healthy men with mildly elevated tHcy concentrations. If high homocysteine concentrations indeed cause cardiovascular disease, choline intake may reduce cardiovascular disease risk in humans. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Dietary biodiversity, defined as the variety of consumed plants, animals and other organisms, can be measured by dietary species richness (DSR). This study investigated associations between DSR and diet quality in Dutch adults. Dietary intake data of 2078 Dutch participants, aged 19 to 79 years, were collected by the Dutch National Food Consumption Survey between 2012 and 2016 via two non-consecutive 24-h dietary recalls. DSR scores were calculated based on the total count of unique species consumed per individual over the two measurement days. An overall DSR score and separate scores for fruit and vegetable species consumption were calculated. The Dutch Healthy Diet index 2015 (DHD15-index) was used to measure diet quality. Linear regression analyses were performed to investigate associations between DSR scores and DHD15-index. Analyses were stratified by age and adjusted for relevant confounders. In total, 157 unique species were identified within the investigated food groups. On average, individuals consumed 13 unique species over two days (SD 4.55). For every additional species consumed, the DHD15-index increased by 1.40 points (95%CI 1.25-1.55). Associations between DSR and DHD15-index were higher in younger adults. DSR fruit showed the strongest associations with DHD15-index (β 4.01 [95%CI 3.65-4.38]). Higher DSR scores are associated with higher diet quality in Dutch adults. These newly developed DSR scores create opportunities for further research to explore the implications of dietary biodiversity in Western diets on health and related outcomes.

Objective: To investigate whether financial constraint and perceived stress modify the effects of food-related taxes on the healthiness of food purchases., Design: Moderation analyses were conducted with data from a trial where participants were randomly exposed to: a control condition with regular food prices, an sugar-sweetened beverage (SSB) tax condition with a two-tiered levy on the sugar content in SSB (5-8 g/100 ml: €0·21 per l and ≥ 8 g/100 ml: €0·28 per l) or a nutrient profiling tax condition where products with Nutri-Score D or E were taxed at a 20 percent level. Outcome measures were overall healthiness of food purchases (%), energy content (kcal) and SSB purchases (litres). Effect modification was analysed by adding interaction terms between conditions and self-reported financial constraint or perceived stress in regression models. Outcomes for each combination of condition and level of effect modifier were visualised., Setting: Virtual supermarket., Participants: Dutch adults ( n 386)., Results: Financial constraint or perceived stress did not significantly modify the effects of food-related taxes on the outcomes. Descriptive analyses suggest that in the control condition, the overall healthiness of food purchases was lowest, and SSB purchases were highest among those with moderate/high levels of financial constraint. Compared with the control condition, in a nutrient profiling tax condition, the overall healthiness of food purchases was higher and SSB purchases were lower, especially among those with moderate/high levels of financial constraint. Such patterns were not observed for perceived stress., Conclusion: Further studies with larger samples are recommended to assess whether food-related taxes differentially affect food purchases of subgroups.

Objective: To measure the effects of health-related food taxes on the environmental impact of consumer food purchases in a virtual supermarket., Design: This is a secondary analysis of data from a randomised controlled trial in which participants were randomly assigned to a control condition with regular food prices ( n 152), an experimental condition with a sugar-sweetened beverage (SSB) tax ( n 131) or an experimental condition with a nutrient profiling tax based on Nutri-Score ( n 112). Participants were instructed to undertake their typical weekly grocery shopping for their households. Primary outcome measures were three environmental impact indicators: greenhouse gas (GHG) emissions, land use and blue water use per household per week. Data were analysed using linear regression analyses., Setting: Three-dimensional virtual supermarket., Participants: Dutch adults (≥ 18 years) who were responsible for grocery shopping in their household ( n 395)., Results: GHG emissions (-7·6 kg CO 2 -eq; 95 % CI -12·7, -2·5) and land use (-3·9 m 2 /year; 95 % CI -7·7, -0·2) were lower for the food purchases of participants in the nutrient profiling tax condition than for those in the control condition. Blue water use was not affected by the nutrient profiling tax. Moreover, the SSB tax had no significant effect on any of the environmental impact indicators., Conclusions: A nutrient profiling tax based on Nutri-Score reduced the environmental impact of consumer food purchases. An SSB tax did not affect the environmental impact in this study.

Poor sleep health is common in older adults and is associated with negative health outcomes. However, the relationship between caffeine consumption and sleep health at an older age is poorly understood. This study investigated the association between caffeine consumption and sleep health in community-dwelling older males and females in The Netherlands. Cross-sectional analyses were performed using data from 1256 participants aged 61-101 years from the Longitudinal Ageing Study Amsterdam. Self-reported questions assessed sleep disturbances (including sleep latency, continuity, and early awakening), sleep duration, and perceived sleep quality. Caffeine consumption was determined with questions about frequency, quantity, and type of coffee and tea consumption. Logistic and linear regression models were used, controlling for potential confounders, and interaction by sex and age was tested. Caffeine consumption showed significant interactions with sex ( p < 0.005) in association with sleep health outcomes. Older females who abstained from caffeine consumption reported more sleep disturbances (β = 0.64 [95%CI 0.13; 1.15]) and had greater odds of short sleep duration (<7 h/day) (OR = 2.26 [95% CI 1.22; 4.20]) compared to those who consumed caffeine. No associations were observed for long sleep duration (>8 h/day) and perceived sleep quality. No associations were observed in older males. Caffeine abstinence was associated with more sleep disturbances and short sleep duration in older females, but not in males. The observed association in older females may reflect reverse causation, suggesting that females may have different motivations for discontinuing caffeine consumption than males.

Food production is responsible for 25% of greenhouse gas emissions and contributes to the overexploitation and pollution of our planet, thereby threatening human health. In order to feed the increasing world population in a healthy and sustainable way, drastic changes are required in both food production and consumption. Not everyone needs to become vegetarian or vegan, but consumption of plant-based foods needs to increase and that of meat and dairy to decrease. These changes are more environmentally sustainable and healthy. Organically grown foods are not always more sustainable, but do contain less synthetic pesticide and antibiotics residues and sometimes more nutrients. Long-term studies are lacking to conclude whether their consumption is healthier. General advices to eat more sustainably and healthy include: prevent overconsumption, avoid food waste, take a few portions of dairy daily, eat less meats and replace meat by plant-based protein sources such as legumes, nuts, soy and cereals.

Purpose: Diet modelling studies suggest that increasing protein intake with no consideration for sustainability results in a higher environmental impact on the diet. To better understand the impact in real life, the aim of this study was to assess the effect of dietary advice to increase protein intake on food consumption and the environmental impact of the diet in community-dwelling older adults., Methods: Food consumption and environmental impact were analyzed among 124 Dutch older adults with lower habitual protein intake (< 1.0 g/kg adjusted body weight/day) participating in the six-month PROMISS trial. Dietary intake data from three 24-h dietary recalls, aided by food diaries, and results from life cycle assessments were used to examine the differences in changes in food consumption and environmental impact between those who received dietary advice to isocalorically increase protein intake to ≥ 1.2 g/kg aBW/d (Protein + ; n = 84) and those who did not receive dietary advice (Control; n = 40)., Results: Compared to the Control, Protein + increased protein intake from animal-based food products (11.0 g protein/d, 95% CI 6.6-15.4, p < 0.001), plant-based food products (2.1 g protein/d, 95% CI 0.2-4.0, p = 0.031) and protein-enriched food products provided during the trial (18 g protein/d, 95% CI 14.5-21.6, p < 0.001) at the 6-month follow-up. Diet-associated greenhouse gas emissions increased by 16% (p < 0.001), land use by 19% (p < 0.001), terrestrial acidification by 20% (p = 0.01), and marine eutrophication by 16% (p = 0.035) in Protein + compared to the Control., Conclusion: This study found that dietary advice increased protein intake, favoring animal-based protein, and increased the environmental impact of the diet in older adults., Trial Registration: ClinicalTrials.gov. NCT03712306. October 2018., (© 2022. The Author(s).)

Background: Reduced meat consumption benefits human and planetary health. Modelling studies have demonstrated the significant health and environmental gains that could be achieved through fiscal measures targeting meat. Adding other interventions may enhance the effect of a fiscal measure. The current study aimed to examine the effect of higher meat prices, an information nudge and a combination of both measures on meat purchases in a three-dimensional virtual supermarket., Methods: A parallel designed randomised controlled trial with four conditions was performed. Participants (≥ 18 years) were randomly assigned to the control condition or one of the experimental conditions: a 30% price increase for meat ('Price condition'), an information nudge about the environmental impact of meat production and consumers' role in that regard ('Information nudge condition') or a combination of both ('Combination condition'). Participants were asked to shop for their household for one week. The primary outcome was the difference in the total amount of meat purchased in grams per household per week., Results: Between 22 June 2020 and 28 August 2020, participants were recruited and randomly assigned to the control and experimental conditions. The final sample included 533 participants. In the 'Combination condition', - 386 g (95% CI: - 579, - 193) meat was purchased compared with the 'Control condition'. Compared to the 'Control condition' less meat was purchased in the 'Price condition' (- 144 g (95%CI: - 331, 43)), although not statistically significant, whereas a similar amount of meat was purchased in the 'Information nudge condition' (1 g (95%CI: - 188, 189))., Conclusion: Achieving the most pronounced effects on reduced meat purchases will require a policy mixture of pricing and informational nudging. Less meat is purchased in a virtual supermarket after raising the meat price by 30% combined with an information nudge. The results could be used to design evidence-based policy measures to reduce meat purchases., Trial Registration: The trial was registered in the Netherlands Trial Register identifier NL8628 . Registered on 18/05/2020. ICTRP Search Portal (who.int) NTR (trialregister.nl)., (© 2022. The Author(s).)

An increasing number of governments worldwide have introduced a tax on sugar-sweetened beverages (SSB) for public health. However, the adoption of such a policy is still debated in many other countries, such as in the Netherlands. We investigated Dutch stakeholder views on taxation of SSB and perceived barriers and facilitators to its adoption in the Netherlands. Semi-structured interviews were conducted in 2019 with 27 stakeholders from health and consumer organizations, health professional associations, trade associations, academia, advisory bodies, ministries and parliamentary parties. Data were analysed using a thematic content approach. The findings reveal that, between and within sectors, stakeholders expressed contradictory views on the effectiveness, appropriateness and (socio)economic effects of an SSB tax. Perceived barriers to the adoption of an SSB tax in the Netherlands included an unfavourable political context, limited advocacy for an SSB tax, a strong lobby against an SSB tax, perceived public opposition, administrative load and difficulties in defining SSB. Perceived facilitators to its adoption included an increasing prevalence of overweight, disappointing results from voluntary industry actions, a change of government, state budget deficits, a shift in public opinion, international recommendations and a solid legal basis. In conclusion, this study shows that several challenges remain to be overcome for the adoption of an SSB tax in the Netherlands. Similar research on stakeholder views in other countries may further inform SSB tax policy processes., (© The Author(s) 2021. Published by Oxford University Press.)

Objective: To investigate the effects of a sugar-sweetened beverage (SSB) tax and a nutrient profiling tax on consumer food purchases in a virtual supermarket., Design: A randomised controlled trial was conducted with a control condition with regular food prices (n 152), an SSB tax condition (n 130) and a nutrient profiling tax condition based on Nutri-Score (n 112). Participants completed a weekly grocery shop for their household. Primary outcome measures were SSB purchases (ordinal variable) and the overall healthiness of the total shopping basket (proportion of total unit food items classified as healthy). The secondary outcome measure was the energy (kcal) content of the total shopping basket. Data were analysed using regression analyses., Setting: Three-dimensional virtual supermarket., Participants: Dutch adults aged ≥18 years are being responsible for grocery shopping in their household (n 394)., Results: The SSB tax (OR = 1·62, (95 % CI 1·03, 2·54)) and the nutrient profiling tax (OR = 1·88, (95 %CI 1·17, 3·02)) increased the likelihood of being in a lower-level category of SSB purchases. The overall healthiness of the total shopping basket was higher (+2·7 percent point, (95 % CI 0·1, 5·3)), and the energy content was lower (-3301 kcal, (95 % CI -6425, -177)) for participants in the nutrient profiling tax condition than for those in the control condition. The SSB tax did not affect the overall healthiness and energy content of the total shopping basket (P > 0·05)., Conclusions: A nutrient profiling tax targeting a wide range of foods and beverages with a low nutritional quality seems to have larger beneficial effects on consumer food purchases than taxation of SSB alone.

Purpose: To examine the cost effectiveness of dietary advice to increase protein intake on 6-month change in physical functioning among older adults., Methods: In this multicenter randomized controlled trial, 276 community-dwelling older adults with a habitual protein intake < 1.0 g/kg adjusted body weight (aBW)/d were randomly assigned to either Intervention 1; advice to increase protein intake to ≥ 1.2 g/kg aBW/d (PROT, n = 96), Intervention 2; similar advice and in addition advice to consume protein (en)rich(ed) foods within half an hour after usual physical activity (PROT + TIMING, n = 89), or continue the habitual diet with no advice (CON, n = 91). Primary outcome was 6-month change in 400-m walk time. Secondary outcomes were 6-month change in physical performance, leg extension strength, grip strength, body composition, self-reported mobility limitations and quality of life. We evaluated cost effectiveness from a societal perspective., Results: Compared to CON, a positive effect on walk time was observed for PROT;  - 12.4 s (95%CI,  - 21.8 to  - 2.9), and for PROT + TIMING;  - 4.9 s (95%CI,  - 14.5 to 4.7). Leg extension strength significantly increased in PROT (+ 32.6 N (95%CI, 10.6-54.5)) and PROT + TIMING (+ 24.3 N (95%CI, 0.2-48.5)) compared to CON. No significant intervention effects were observed for the other secondary outcomes. From a societal perspective, PROT was cost effective compared to CON., Conclusion: Dietary advice to increase protein intake to ≥ 1.2 g/kg aBW/d improved 400-m walk time and leg strength among older adults with a lower habitual protein intake. From a societal perspective, PROT was considered cost-effective compared to CON. These findings support the need for re-evaluating the protein RDA of 0.8 g/kg BW/d for older adults., Trial Registration: The trial has been registered at ClinicalTrials.gov (NCT03712306). Date of registration: October 2018. Registry name: The (Cost) Effectiveness of Increasing Protein Intake on Physical Functioning in Older Adults. Trial Identifier: NCT03712306., (© 2021. The Author(s).)

This study investigated ethnic differences in childhood body mass index (BMI) in children from Dutch and Turkish descent and the role of infant feeding factors (breastfeeding duration, milk feeding frequency, as well as the timing, frequency and variety of complementary feeding (CF)). We used data from 244 children (116 Dutch and 128 Turkish) participating in a prospective study in the Netherlands. BMI was measured at 2, 3 and 5 years and standard deviation scores (sds) were derived using WHO references. Using linear mixed regression analyses, we examined ethnic differences in BMI-sds between 2 and 5 years, and the role of infant feeding in separate models including milk or CF factors, or both (full model). Relative to Dutch children, Turkish children had higher BMI-sds at age 3 (mean difference: 0.26; 95%CI: 0.04, 0.48) and 5 (0.63; 0.39, 0.88), but not at 2 years (0.08; -0.16, 0.31). Ethnic differences in BMI-sds were somewhat attenuated by CF factors at age 3 (0.16; -0.07, 0.40) and 5 years (0.50; 0.24, 0.77), whereas milk feeding had a minor impact. Of all factors, only CF variety was associated with BMI-sds in the full model. CF factors, particularly CF variety, explain a small fraction of the BMI-sds differences between Dutch and Turkish children. The role of CF variety on childhood BMI requires further investigation.

Limited and inconsistent evidence exists on the associations between dietary patterns and overweight during childhood. The present study describes dietary patterns of three-year-old Dutch children and associations between childhood overweight and body mass index (BMI) development between 3 and 10 years. In the GECKO Drenthe birth cohort (N = 1306), body height and weight were measured around the age of 3, 4, 5, and 10 years, and overweight was defined according to Cole and Lobstein. A validated food frequency questionnaire (FFQ) was used to measure diet at 3 years. Dietary patterns were derived using principal components analysis (PCA). Using logistic regression analyses, pattern scores were related to overweight at 3 and 10 years. A linear mixed-effect model was used to estimate BMI-SDS development between 3 to 10 years according to quartiles of adherence to the pattern scores. Two dietary patterns were identified: (1) 'minimally processed foods', indicating high intakes of vegetables/sauces/savory dishes, and (2) 'ultra-processed foods', indicating high intakes of white bread/crisps/sugary drinks. A 1 SD increase in the 'ultra-processed foods' pattern score increased the odds of overweight at 10 years (adjusted OR: 1.30; 95%CI: 1.08, 1.57; p = 0.006). The 'minimally processed foods' pattern was not associated with overweight. Although a high adherence to both dietary patterns was associated with a higher BMI-SDS up to 10 years of age, a stronger association for the 'ultra-processed foods' pattern was observed ( p < 0.001). A dietary pattern high in energy-dense and low-fiber ultra-processed foods at 3 years is associated with overweight and a high BMI-SDS later in childhood.

Objective: To investigate the level of public acceptability of a sugar-sweetened beverage (SSB) tax and its associated factors., Design: Participants completed an online self-administered questionnaire. Acceptability of an SSB tax was measured on a seven-point Likert scale (strongly disagree to strongly agree). Associations between acceptability and sociodemographic factors, weight status, SSB consumption and beliefs about effectiveness (e.g., 'An SSB tax would reduce people's SSB consumption'), appropriateness, socioeconomic and economic benefit, implementation and trust were assessed using multivariable linear regression analyses., Setting: The Netherlands., Participants: Dutch adults aged ≥18 years representative of the Dutch population for age, sex, education level and location (n 500)., Results: Of the participants, 40 % supported and 43 % opposed an SSB tax in general. Moreover, 42 % supported (43 % opposed) an SSB tax as a strategy to reduce overweight, and 55 % supported (32 % opposed) an SSB tax if revenue is used for health initiatives. Participants with a low education level (B = -0·82, 95 % CI -1·31, -0·32), overweight (B = -0·49, 95 % CI -0·89, -0·09), moderate or high SSB consumption (B = -0·86, 95 % CI -1·30, -0·43 and B = -1·01, 95 % CI -1·47, -0·56, respectively) and households with adolescents (B = -0·57, 95 % CI -1·09, -0·05) reported a lower acceptability of an SSB tax than their counterparts. Beliefs about effectiveness, appropriateness, socioeconomic and economic benefit, implementation and trust were associated with acceptability (P < 0·001)., Conclusions: Public acceptability of an SSB tax tends to be higher if revenue is used for health initiatives. The factors associated with acceptability should be taken into consideration.

Background: Milk feeding type (exclusive breastfeeding [EBF], formula feeding or mixed feeding) and timing of complementary feeding (CF) have been associated with infant growth. However, studies evaluating their combined role, and the role of ethnicity, are scarce. We examined associations of feeding patterns (milk feeding type combined with timing of CF) with infant body mass index (BMI) trajectories and potential ethnic-specific associations., Methods: Infant feeding and BMI data during the 1st year of life from 3524 children (Dutch n = 2880, Moroccan n = 404 and Turkish n = 240) from the Amsterdam Born Children and their Development (ABCD) cohort were used. Six feeding patterns were defined: EBF/earlyCF, EBF/lateCF (reference), formula/earlyCF, formula/lateCF, mixed/earlyCF and mixed/lateCF. A covariate adjusted latent class mixed model was applied to simultaneously model BMI trajectories and associations with feeding patterns. Potential ethnic differences in the associations were studied in a separate model where interactions between ethnicity and feeding patterns were included., Results: Four distinct BMI trajectories (low, mid-low, mid-high and high) were identified. Feeding pattern of formula/earlyCF was associated with lower odds for low (OR: 0.43; 95% CI: 0.25, 0.76) or mid-high (0.28; 0.16, 0.51) (ref: high) trajectory compared with EBF/lateCF pattern (ref). An ethnic-specific model revealed that among Dutch infants, formula/earlyCF pattern was associated with lower odds for low trajectory (0.46; 0.24, 0.87), whereas among Turkish/Moroccan infants almost all feeding patterns were associated with lower odds for the low trajectory (ref: high)., Conclusion: Infant feeding patterns are associated with early BMI trajectories with specific ethnic differences. Future studies should take the role of ethnicity into account in the associations between infant feeding and growth.

Background: Protein intake greater than the currently recommended amount is suggested to improve physical functioning and well-being in older adults, yet it is likely to increase diet-associated greenhouse gas emissions (GHGEs) if environmental sustainability is not considered., Objectives: We aimed to identify dietary changes needed to increase protein intake while improving diet environmental sustainability in older adults., Methods: Starting from the habitual diet of 1,354 Dutch older adults (aged 56-101 y) from the Longitudinal Aging Study Amsterdam cohort, mathematical diet optimization was used to model high-protein diets with minimized departure from habitual intake in cumulative steps. First, a high-protein diet defined as that providing ≥1.2 g protein · kg body weight-1 · d-1 was developed isocalorically while maintaining or improving nutritional adequacy of the diet. Second, adherence to the Dutch food-based dietary guidelines (FBDG) was imposed. Third, a stepwise 10% GHGE reduction was applied., Results: Achieving a high-protein diet aligned with the FBDG without considering GHGEs required an increase in vegetables, legumes, nuts, whole grains, meat/dairy alternatives, dairy, and eggs and a reduction in total meat (for men only) and discretionary products, but it resulted in a 5% increase in GHGEs in men and 9% increase in women. When a stepwise GHGE reduction was additionally applied, increases in poultry and pork (mainly for women) and decreases in beef/lamb and processed meat were accrued, with total meat staying constant until a 50-60% GHGE reduction. Increases in whole grains, nuts, and meat/dairy alternatives and decreases in discretionary products were needed to lower GHGEs., Conclusions: A high-protein diet aligned with FBDG can be achieved in concert with reductions in GHGEs in Dutch older adults by consuming no more than the recommended 500 g meat per week while replacing beef and lamb and processed meat with poultry and pork and increasing intake of diverse plant-protein sources., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Socioeconomic inequalities in overweight and obesity exist in many European countries. A sugar-sweetened beverages (SSB) tax may contribute to a reduction of these inequalities. However, in the Netherlands, the government decided to not (yet) introduce an SSB tax, although the government has acknowledged its potential to be pro-equity. Understanding how various stakeholder groups perceive the potential effects of an SSB tax on different socioeconomic groups may provide useful insights into equity-related considerations in the debate whether or not to implement an SSB tax. This study aims to gain insight into the perceptions of stakeholder groups in the Netherlands on (1) the effects of an SSB tax on the budgets of lower and higher socioeconomic groups and (2) the impact of an SSB tax on socioeconomic inequalities in dietary intake and health., Methods: Semi-structured interviews were conducted in 2019 with 27 participants from various stakeholder groups in the Netherlands (i.e. health and consumer organizations, health professional associations, trade associations, academia, advisory bodies, ministries and parliamentary parties). Data were analyzed using a thematic content approach., Results: Participants from all stakeholder groups indicated that an SSB tax would have a larger impact on the budgets of lower socioeconomic groups. Participants from nearly all stakeholder groups (except trade associations) mentioned that an SSB tax could have greater health benefits among lower socioeconomic groups as these often have a higher SSB consumption and are more likely to be overweight or obese. Some participants mentioned that an SSB tax may have no or adverse health effects among lower socioeconomic groups (e.g. compensation of lower SSB consumption with other unhealthy behaviours). Some participants emphasised that an SSB tax should only be introduced when accompanied by other interventions (e.g. offering healthy alternatives), to make it easier for lower socioeconomic groups to lower their SSB consumption in response to an SSB tax, and to prevent adverse health effects., Conclusions: Participants believed an SSB tax could contribute to a reduction in socioeconomic inequalities in dietary intake and health. However, additional interventions facilitating the reduction of SSB consumption in lower socioeconomic groups were recommended.

Introduction: Short-term metabolic and observational studies suggest that protein intake above the recommended dietary allowance of 0.83 g/kg body weight (BW)/day may support preservation of lean body mass and physical function in old age, but evidence from randomised controlled trials is inconclusive., Methods and Analysis: The PRevention Of Malnutrition In Senior Subjects in the EU (PROMISS) trial examines the effect of personalised dietary advice aiming at increasing protein intake with or without advice regarding timing of protein intake to close proximity of usual physical activity, on change in physical functioning after 6 months among community-dwelling older adults (≥65 years) with a habitual protein intake of <1.0 g/kg adjusted (a)BW/day. Participants (n=264) will be recruited in Finland and the Netherlands, and will be randomised into three groups; two intervention groups and one control group. Intervention group 1 (n=88) receives personalised dietary advice and protein-enriched food products in order to increase their protein intake to at least 1.2 g/kg aBW/day. Intervention group 2 (n=88) receives the same advice as described for intervention group 1, and in addition advice to consume 7.5-10 g protein through protein-(en)rich(ed) foods within half an hour after performing usual physical activity. The control group (n=88) receives no intervention. All participants will be invited to attend lectures not related to health. The primary outcome is a 6-month change in physical functioning measured by change in walk time using a 400 m walk test. Secondary outcomes are: 6-month change in the Short Physical Performance Battery score, muscle strength, body composition, self-reported mobility limitations, quality of life, incidence of frailty, incidence of sarcopenia risk and incidence of malnutrition. We also investigate cost-effectiveness by change in healthcare costs., Discussion: The PROMISS trial will provide evidence whether increasing protein intake, and additionally optimising the timing of protein intake, has a positive effect on the course of physical functioning after 6 months among community-dwelling older adults with a habitual protein intake of <1.0 g/kg aBW/day., Ethics and Dissemination: The study has been approved by the Ethics Committee of the Helsinki University Central Hospital, Finland (ID of the approval: HUS/1530/2018) and The Medical Ethical Committee of the Amsterdam UMC, location VUmc, Amsterdam, the Netherlands (ID of the approval: 2018.399). All participants provided written informed consent prior to being enrolled onto the study. Results will be submitted for publication in peer-reviewed journals and will be made available to stakeholders (ie, older adults, healthcare professionals and industry)., Trial Registration Number: ClinicalTrials.gov Registry (NCT03712306)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Food-based dietary guidelines are proposed to not only improve diet quality, but to also reduce the environmental impact of diets. The aim of our study was to investigate whether food-related behavioral activation therapy (F-BA) applying Mediterranean-style dietary guidelines altered food intake and the environmental impact of the diet in overweight adults with subsyndromal symptoms of depression., Methods: In total 744 adults who either received the F-BA intervention (F-BA group) or no intervention (control group) for 12 months were included in this analysis. Food intake data were collected through a food frequency questionnaire at baseline and after 6 and 12 months. Greenhouse gas emissions (GHGE), land use (LU), and fossil energy use (FEU) estimates from life-cycle assessments and a weighted score of the three (pReCiPe score) were used to estimate the environmental impact of each individual diet at each timepoint., Results: The F-BA group reported increased intakes of vegetables (19.7 g/day; 95% CI 7.8-31.6), fruit (23.0 g/day; 9.4-36.6), fish (7.6 g/day; 4.6-10.6), pulses/legumes (4.0 g/day; 1.6-6.5) and whole grains (12.7 g/day; 8.0-17.5), and decreased intake of sweets/extras (- 6.8 g/day; - 10.9 to - 2.8) relative to control group. This effect on food intake resulted in no change in GHGE, LU, and pReCiPe score, but a relative increase in FEU by 1.6 MJ/day (0.8, 2.4)., Conclusions: A shift towards a healthier Mediterranean-style diet does not necessarily result in a diet with reduced environmental impact in a real-life setting., Trial Registration: ClinicalTrials.gov. Number of identification: NCT02529423. August 2015.

Background: Taxation of sugar-sweetened beverages (SSBs), as a component of a comprehensive strategy, has emerged as an apparent effective intervention to counteract the rising prevalence of overweight and obesity. Insight into the political and public acceptability may help adoption and implementation in countries with governments that are considering an SSBs tax. Hence, we aimed to conduct a systematic review and meta-analysis to synthesize the existing qualitative and quantitative literature on political and public acceptability of an SSBs tax., Methods: Four electronic databases (PubMed, Embase, Scopus, Web of Science) were searched until November 2018. The methodological quality of the included studies was assessed using the Mixed Methods Appraisal Tool. Qualitative studies were analyzed using a thematic synthesis. Quantitative studies were analyzed using a random-effects meta-analysis for the pooling of proportions., Results: Thirty-seven articles reporting on forty studies were eligible for inclusion. Five themes derived from the thematic synthesis: (i) beliefs about effectiveness and cost-effectiveness, (ii) appropriateness, (iii) economic and socioeconomic benefit, (iv) policy adoption and implementation, and (v) public mistrust of the industry, government and public health experts. Results of the meta-analysis indicated that of the public 42% (95% CI = 0.38-0.47) supports an SSBs tax, 39% (0.29-0.50) supports an SSBs tax as a strategy to reduce obesity, and 66% (0.60-0.72) supports an SSBs tax if revenue is used for health initiatives., Conclusions: Beliefs about effectiveness and cost-effectiveness, appropriateness, economic and socioeconomic benefit, policy adoption and implementation, and public mistrust of the industry, government and public health experts have important implications for the political and public acceptability of an SSBs tax. We provide recommendations to increase acceptability and enhance successful adoption and implementation of an SSBs tax: (i) address inconsistencies between identified beliefs and scientific literature, (ii) use raised revenue for health initiatives, (iii) communicate transparently about the true purpose of the tax, and (iv) generate political priority for solutions to the challenges to implementation.

Objective: To examine associations of diet quality indicators with 4-year incidence of frailty in community-dwelling older adults., Design: Prospective cohort study., Setting: Health, Aging, and Body Composition Study, United States., Participants: Community-dwelling men and women, aged 70 to 81 years in 1998 to 1999 (first follow-up, present study's baseline; n = 2154)., Measurements: At first follow-up, dietary intake over the preceding year was assessed with a food frequency questionnaire. Indicators of diet quality include the Healthy Eating Index (categorized as poor, medium, and good), energy intake, and protein intake (a priori adjusted for energy intake using the nutrient residual model). Frailty status was determined using Fried's five-component frailty phenotype and categorized into "robust" (0 components present), "pre-frailty" (1 - 2 components present), or "frail" (3-5 components present). Cox proportional hazards analysis was used to examine associations of the diet quality indicators with 4-year incidence of (1) frailty and (2) pre-frailty or frailty. Competing risk analysis was used to examine associations with frailty by accounting for competing risks of death., Results: During the 4-year follow-up, 277 of the 2154 participants, robust or pre-frail at baseline, developed frailty, and 629 of the 1020 participants, robust at baseline, developed pre-frailty or frailty. Among the robust and pre-frail, after adjustment for confounders including energy intake, those consuming poor- and medium-quality diets had a higher frailty incidence than those consuming good-quality diets (hazard ratio [HR] = 1.92 [95% confidence interval {CI} = 1.17-3.17] and HR = 1.40 [95% CI = 0.99-1.98], respectively). No associations for energy or protein intake were observed. Competing risk analyses yielded similar results. Among the robust, those with lower vegetable protein intake had a higher "pre-frailty or frailty" incidence (per -10 g/d: HR = 1.20; 95% CI = 1.04-1.39). No other associations were observed., Conclusion: Poorer overall diet quality and lower vegetable protein intake may increase the risk of becoming frail in old age. We found no association for intakes of energy, total protein, or animal protein. J Am Geriatr Soc 67:1835-1842, 2019., (© 2019 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.)

Protein-energy malnutrition (PEM) is a growing concern on account of an aging population and its negative health consequences. While dietary protein plays a key role in the prevention of PEM, it also plays a pivotal role in the environmental impact of the human diet. In search for sustainable dietary strategies to increase protein intake in older adults, this study investigated the readiness of older adults to accept the consumption of the following alternative, more sustainable protein sources: plant-based protein, insects, single-cell protein, and in vitro meat. Using ordinal logistic regression modeling, the associations of different food-related attitudes and behavior and sociodemographics with older adults' acceptance to consume such protein sources were assessed. Results were obtained through a consumer survey among 1825 community-dwelling older adults aged 65 years or above in five EU countries (United Kingdom, the Netherlands, Poland, Spain, and Finland). Dairy-based protein was generally the most accepted protein source in food products (75% of the respondents found its consumption acceptable or very acceptable). Plant-based protein was the most accepted alternative, more sustainable protein source (58%) followed by single-cell protein (20%), insect-based protein (9%), and in vitro meat-based protein (6%). We found that food fussiness is a barrier to acceptance, whereas green eating behavior and higher educational attainment are facilitators to older adults' acceptance to eat protein from alternative, more sustainable sources. Health, sensory appeal, and price as food choice motives, as well as gender and country of residence were found to influence acceptance, although not consistently across all the protein sources. Findings suggest that there is a window of opportunity to increase older adults' acceptance of alternative, more sustainable protein sources and in turn increase protein intake in an environmentally sustainable way in EU older adults.

Introduction: Research in adults shows high intakes of sugar-sweetened beverages (SSBs) increases blood pressure (BP), however evidence in children is scarce and inconclusive. No studies have investigated autonomic nervous system (ANS) activation due to SSBs in children. Our aim was to investigate the associations between SSBs intake, BP and ANS activation in children., Methods: Cross-sectional data collected in 2008-2010 at age 5/6 (n = 2519) and in 2015-2016 at age 11/12 (n = 769) years in the Amsterdam Born Children and their Development-study were analyzed in 2017. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as pre-ejection period (PEP; sympathetic activation) and respiratory sinus arrhythmia (RSA; parasympathetic activation) were measured during supine position. SSBs intake was self-reported., Results: After adjustments for covariates, including weight status, no associations between SSBs intake, BP and ANS measures were found at age 5/6. At age 11/12, one serving/day increase in SSBs was associated with 0.8 mmHg increase in SBP (95%CI:0.4; 1.2), 0.3 mmHg increase in DBP (0.0; 0.5) and 0.9 msec decrease in PEP (-1.5;-0.2). Children in the highest SSBs tertile had an increase of 2.3 mmHg in SBP (0.7; 4.0) and a decrease of 3.6 msec in PEP (-6.7;-0.6) compared to children in the lowest tertile., Conclusion: In children aged 11/12, high intake of SSBs was associated with increased BP, which might be due to increased sympathetic nervous system activation. Importantly, these associations were independent of weight status., (Copyright © 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Objective: Inadequate maternal micronutrient status during pregnancy can lead to short- and long-term health risks for mother and offspring. The present study investigated the association between pre-pregnancy weight status and micronutrient status during pregnancy., Design: Maternal blood samples were collected during early pregnancy (median 13, interquartile range 12-15 weeks) and were assayed for serum folate, ferritin, Fe and vitamin B12. Regression modelling was used to assess the association between pre-pregnancy underweight, normal weight, overweight and obesity, and micronutrient levels, as well as the odds for deficiencies., Setting: The Amsterdam Born Children and their Development (ABCD) study, the Netherlands., Subjects: Women with singleton pregnancies without diabetes (n 4243)., Results: After adjustment for covariates, overweight women and obese women had lower (β; 95 % CI) folate (-1·2; -2·2, -0·2 and -2·3; -4·0, -0·7 nmol/l, respectively) and Fe (-1·7; -2·3, -1·1 and -3·6; -4·7, -2·6 μmol/l, respectively) levels than women with normal weight. Furthermore, overweight women had 6 % (95 % CI -9, -3 %) and obese women had 15 % (-19, -10 %), lower vitamin B12 levels, and obese women had 19 % (6, 32 %) higher ferritin levels, than normal-weight women. Obese women had higher odds (OR; 95 % CI) for folate deficiency (2·03; 1·35, 3·06), Fe deficiency (3·26; 2·09, 5·08) and vitamin B12 deficiency (2·05; 1·41, 2·99) than women with normal weight. Underweight was not associated with micronutrient status., Conclusions: During early pregnancy, women with pre-pregnancy overweight and obesity had lower serum folate, Fe and vitamin B12 status. This resulted in increased risk of serum folate, Fe and vitamin B12 deficiencies in women with obesity.

Background: Protein-energy malnutrition (PEM) is a major problem in older adults. Whether poor diet quality is an indicator for the long-term development of PEM is unknown., Objective: The aim was to determine whether poor diet quality is associated with the incidence of PEM in community-dwelling older adults., Design: We used data on 2234 US community-dwelling older adults aged 70-79 y of the Health, Aging, and Body Composition (Health ABC) Study. In 1998-1999, dietary intake over the preceding year was measured by using a Block food-frequency questionnaire. Indicators of diet quality include the Healthy Eating Index (HEI), energy intake, and protein intake. Outcomes were determined annually by using measured weight and height and included the following: 1) incident PEM [body mass index (in kg/m2) <20, involuntary weight loss of ≥5% in the preceding year at any follow-up examination, or both] and 2) incident persistent PEM (having PEM at 2 consecutive follow-up examinations). Associations of indicators of diet quality with 4-y and 3-y incidence of PEM and persistent PEM, respectively, were examined by multivariable Cox regression analyses., Results: The quality of the diet, as assessed with the HEI, was rated as "poor" for 6.4% and as "needs improvement" for 73.0% of the participants. During follow-up, 24.9% of the participants developed PEM and 8.5% developed persistent PEM. A poor HEI score was not associated with incident PEM or persistent PEM. Lower baseline energy intake was associated with a lower incidence of PEM (HR per 100-kcal/d lower intake: 0.98; 95% CI: 0.97, 0.99) and persistent PEM (HR: 0.97; 95% CI: 0.95, 0.99), although lower baseline protein intake was observed to be associated with a higher incidence of persistent PEM (HR per 10-g/d lower intake: 1.15; 95% CI: 1.03, 1.29)., Conclusions: These findings do not indicate that a poor diet quality is a risk factor for the long-term development of PEM in community-dwelling older adults, although there is an indication that lower protein intake is associated with higher PEM risk.

Aims/hypothesis: Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA 1c , fasting insulin and HOMA-IR with incident type 2 diabetes mellitus., Methods: The study population included 1349 participants aged 50-75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations., Results: After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA 1c , 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA 1c with incident diabetes were non-linear, rising more steeply at higher values., Conclusions/interpretation: FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA 1c , HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers.

Background: Substituting sugar-free for sugar-sweetened beverages reduces weight gain. This effect may be more pronounced in children with a high body mass index (BMI) because their sensing of kilocalories might be compromised. We investigated the impact of sugar-free versus sugary drinks separately in children with a higher and a lower initial BMI z score, and predicted caloric intakes and degree of compensation in the two groups., Methods and Findings: This is a secondary, explorative analysis of our double-blind randomized controlled trial (RCT) which showed that replacement of one 250-mL sugary drink per day by a sugar-free drink for 18 months significantly reduced weight gain. In the 477 children who completed the trial, mean initial weights were close to the Dutch average. Only 16% were overweight and 3% obese. Weight changes were expressed as BMI z-score, i.e. as standard deviations of the BMI distribution per age and sex group. We designated the 239 children with an initial BMI z-score below the median as 'lower BMI' and the 238 children above the median as 'higher BMI'. The difference in caloric intake from experimental beverages between treatments was 86 kcal/day both in the lower and in the higher BMI group. We used a multiple linear regression and the coefficient of the interaction term (initial BMI group times treatment), indicated whether children with a lower BMI responded differently from children with a higher BMI. Statistical significance was defined as p ≤ 0.05. Relative to the sugar sweetened beverage, consumption of the sugar-free beverage for 18 months reduced the BMI z-score by 0.05 SD units within the lower BMI group and by 0.21 SD within the higher BMI group. Body weight gain was reduced by 0.62 kg in the lower BMI group and by 1.53 kg in the higher BMI group. Thus the treatment reduced the BMI z-score by 0.16 SD units more in the higher BMI group than in the lower BMI group (p = 0.04; 95% CI -0.31 to -0.01). The impact of the intervention on body weight gain differed by 0.90 kg between BMI groups (p = 0.09; 95% CI -1.95 to 0.14). In addition, we used a physiologically-based model of growth and energy balance to estimate the degree to which children had compensated for the covertly removed sugar kilocalories by increasing their intake of other foods. The model predicts that children with a lower BMI had compensated 65% (95% CI 28 to 102) of the covertly removed sugar kilocalories, whereas children with a higher BMI compensated only 13% (95% CI -37 to 63)., Conclusions: The children with a BMI above the median might have a reduced tendency to compensate for changes in caloric intake. Differences in these subconscious compensatory mechanisms may be an important cause of differences in the tendency to gain weight. If further research bears this out, cutting down on the intake of sugar-sweetened drinks may benefit a large proportion of children, especially those who show a tendency to become overweight., Trial Registration: ClinicalTrials.gov NCT00893529.

Background: Replacement of sugar-sweetened by non-nutritively sweetened beverages or water may reduce excess weight gain in children. However, it is unclear whether children like non-nutritively sweetened beverages as much as sugar-sweetened beverages. We examined whether children could taste a difference between non-nutritively sweetened beverages and matching sugar-sweetened beverages, and which of the two types of beverage they liked best., Methods: 89 children aged 5 to 12 tasted seven non-nutritively sweetened beverages and matching sugar-sweetened beverages, for a total of 14 beverages. We used Triangle tests to check their ability to discriminate between the matched versions, and a 5-point scale to measure how much the children liked each individual beverage., Results: Overall, 24% of children appeared to be genuinely capable of distinguishing between non-nutritively sweetened and sugar-sweetened beverages. The mean ± SD score for how much the children liked the non-nutritively sweetened beverages was 3.39 ± 0.7 and that for the sugar-sweetened beverages 3.39 ± 0.6 (P = 0.9) on a scale running from 1 (disgusting) to 5 (delicious). The children preferred some beverages to others irrespective of whether they were sugar-sweetened or non-nutritively sweetened (P = 0.000). Children who correctly identified which of three drinks contained the same sweetener and which one was different also showed no preference for either type., Conclusion: We found that about one in four children were able to discriminate between non-nutritively sweetened and sugar-sweetened beverages but children liked both varieties equally. Non-nutritively sweetened beverages may therefore be an acceptable alternative to sugar-sweetened beverages although water remains the healthiest beverage for children.

Background: Substituting sugar-free for sugar-sweetened beverages reduces weight gain. A possible explanation is that sugar-containing and sugar-free beverages cause the same degree of satiety. However, this has not been tested in long-term trials., Methods: We randomized 203 children aged 7-11 years to receive 250 mL per day of an artificially sweetened sugar-free beverage or a similarly looking and tasting sugar-sweetened beverage. We measured satiety on a 5-point scale by questionnaire at 0, 6, 12 and 18 months. We calculated the change in satiety from before intake to 1 minute after intake and 15 minutes after intake. We then calculated the odds ratio that satiety increased by 1 point in the sugar-group versus the sugar-free group. We also investigated how much the children liked and wanted the beverages., Results: 146 children or 72% completed the study. We found no statistically significant difference in satiety between the sugar-free and sugar-sweetened group; the adjusted odds ratio for a 1 point increase in satiety in the sugar group versus the sugar-free group was 0.77 at 1 minute (95% confidence interval, 0.46 to 1.29), and 1.44 at 15 minutes after intake (95% CI, 0.86 to 2.40). The sugar-group liked and wanted their beverage slightly more than the sugar-free group, adjusted odds ratio 1.63 (95% CI 1.05 to 2.54) and 1.65 (95% CI 1.07 to 2.55), respectively., Conclusions: Sugar-sweetened and sugar-free beverages produced similar satiety. Therefore when children are given sugar-free instead of sugar-containing drinks they might not make up the missing calories from other sources. This may explain our previous observation that children in the sugar-free group accumulated less body fat than those in the sugar group., Trial Registration: ClinicalTrials.gov NCT00893529 http://clinicaltrials.gov/show/NCT00893529.

Objective: To investigate the relationship between the intake of sugar-containing beverages (SCB) at the age of 13 years and adult weight status 24–30 years later., Design: A longitudinal study with 30 years of follow-up from adolescence (age 13 years in 1976) to adulthood (up to 2000 and 2006). Dietary intake was assessed through cross-check dietary history face-to-face interviews by a dietitian. Beverages were divided into two categories: (i) total SCB and (ii) SCB excluding 100% fruit juices. Percentage of total fat (%total fat) and percentage of trunk fat (%trunk fat) were obtained through dual-energy X-ray absorptiometry measurements; body weight and height were measured by trained staff., Setting: Amsterdam Growth and Health Longitudinal Study, the Netherlands., Subjects: One hundred and fourteen males and 124 females., Results: In males, but not in females, each additional daily serving of SCB excluding 100% fruit juices at 13 years was associated with 1?14% higher %total fat (95% CI 0?04, 2?23 %; P50?04) and 1?62% higher %trunk fat (95% CI 0?14, 3?10 %; P50?03) in adulthood after correction for confounders. No statistically significant relationship was found between the intake of SCB excluding 100% fruit juices at the age of 13 and BMI in both sexes. In addition, no statistically significant relationships were found between the intake of total SCB and all measures of adult weight status in both sexes., Conclusions: Intake of SCB excluding 100% fruit juices at the age of 13 years was positively associated with adult %total fat and %trunk fat in males, but not in females.

Background: The consumption of beverages that contain sugar is associated with overweight, possibly because liquid sugars do not lead to a sense of satiety, so the consumption of other foods is not reduced. However, data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain., Methods: We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age. Participants were randomly assigned to receive 250 ml (8 oz) per day of a sugar-free, artificially sweetened beverage (sugar-free group) or a similar sugar-containing beverage that provided 104 kcal (sugar group). Beverages were distributed through schools. At 18 months, 26% of the children had stopped consuming the beverages; the data from children who did not complete the study were imputed., Results: The z score for the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group; the 95% confidence interval (CI) of the difference was -0.21 to -0.05. Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group (95% CI for the difference, -1.54 to -0.48). The skinfold-thickness measurements, waist-to-height ratio, and fat mass also increased significantly less in the sugar-free group. Adverse events were minor. When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study, the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group (P=0.06)., Conclusions: Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children. (Funded by the Netherlands Organization for Health Research and Development and others; DRINK ClinicalTrials.gov number, NCT00893529.).

Background: Intake of sugar-sweetened beverages is associated with overweight in observational studies. A possible explanation is that liquid sugars do not satiate and that their intake is not compensated by reduced caloric intake from other foods. However, evidence from intervention studies for this hypothesis is inconclusive because previous studies were not blinded. Hence results may have been influenced by expectations and behavioral cues rather than by physiological mechanisms., Methods: We designed the Double-blind, Randomized INtervention study in Kids (DRINK) to examine the effect on body weight of covertly replacing sugar-sweetened by sugar-free beverages. Children were only eligible if they habitually drank sugar-sweetened beverages. We recruited 642 healthy children (mean age 8.2, range 4.8-11.9). We designed, tested and produced custom-made beverages containing 10% sugar and sugar-free beverages with the same sweet taste and look. Children receive one 250 mL can of study beverage daily for 18 months. We perform body measurements at 0, 6, 12 and 18 months. The primary outcome is the z-score of BMI for age. The maximum predicted difference in this score between groups is 0.72, which corresponds with a difference in body weight of 2.3 kg., Discussion: The double-blind design eliminates behavioral factors that affect body weight. If children gain less body fat when drinking sugar-free than when drinking sugar-sweetened beverages that would show that liquid sugar indeed bypasses biological satiation mechanisms. It would also suggest that a reduction in liquid sugars could decrease body fat more effectively than reduction of other calorie sources., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Coffee consumption is associated with a lower risk of type 2 diabetes. We tested the hypothesis that this is mediated by incretin hormones by measuring the acute effects of decaffeinated coffee and coffee components on GLP-1 and GIP concentrations. A randomized cross-over trial of the effects of 12 g decaffeinated coffee, 1 g chlorogenic acid, 500 mg trigonelline, and placebo on total and intact GLP-1 and GIP concentrations during an oral glucose tolerance test took place in fifteen overweight men. No treatment significantly affected the overall GLP-1 or GIP secretion pattern following an OGTT relative to placebo. Decaffeinated coffee slightly increased total GLP-1 concentration 30 minutes after ingestion (before the OGTT) relative to placebo (2.7 pmol/L, p = 0.03), but this change did not correspond with changes in glucose or insulin secretion. These findings do not support the hypothesis that coffee acutely improves glucose tolerance through effects on the secretion of incretin hormones. Chronic effects of coffee and its major components still need to be investigated.

Objective: Coffee consumption has been associated with lower risk of type 2 diabetes. We evaluated the acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance., Research Design and Methods: We conducted a randomized crossover trial of the effects of 12 g decaffeinated coffee, 1 g chlorogenic acid, 500 mg trigonelline, and placebo (1 g mannitol) on glucose and insulin concentrations during a 2-h oral glucose tolerance test (OGTT) in 15 overweight men., Results: Chlorogenic acid and trigonelline ingestion significantly reduced glucose (-0.7 mmol/l, P = 0.007, and -0.5 mmol/l, P = 0.024, respectively) and insulin (-73 pmol/l, P = 0.038, and -117 pmol/l, P = 0.007) concentrations 15 min following an OGTT compared with placebo. None of the treatments affected insulin or glucose area under the curve values during the OGTT compared with placebo., Conclusions: Chlorogenic acid and trigonelline reduced early glucose and insulin responses during an OGTT.

Background: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease (CVD). Preliminary evidence suggests a role for global DNA hypomethylation in the pathogenesis of atherosclerotic complications in CKD. The aims of this study in patients with stage 2-4 CKD were (1) to assess the association between renal function and DNA methylation, (2) to assess the association between DNA methylation and two markers of atherosclerosis [common carotid intima-media thickness (CCA-IMT)] and brachial artery endothelium-dependent, flow-mediated dilatation (BA-FMD) and (3) to examine the effect of a multi-step treatment strategy on DNA methylation., Methods: In the Anti-Oxidant Therapy In Chronic Renal Insufficiency study (ATIC-study), 93 patients with stage 2-4 CKD were included. In a randomized, double-blind, placebo-controlled design, the treatment group received pravastatin to which vitamin E was added after 6 months and homocysteine-lowering B-vitamin therapy after another 6 months. DNA methylation was assessed using tandem mass spectrometry. CCA-IMT and BA-FMD were assessed using B-mode ultrasonography., Results: At baseline, global DNA methylation was not associated with the estimated glomerular filtration rate (P = 0.32) or with CCA-IMT (P = 0.62) or BA-FMD (P = 0.51). No effect of the treatment strategy including B-vitamin on global DNA methylation was found either in the total study group or within separate strata of homocysteine concentration and renal function., Conclusion: In patients with stage 2-4 CKD, global DNA methylation is not associated with renal function or with CCA-IMT or BA-FMD. A treatment strategy that includes B-vitamins did not alter global DNA methylation in these patients. These data do not support the role of DNA hypomethylation in CKD-associated vascular disease in patients with stage 2-4 CKD.

Objective: To investigate the association between dietary intakes of folate, betaine and choline and the risk of cardiovascular disease (CVD)., Design: Prospective cohort study., Subjects: A total of 16 165 women aged 49-70 years without prior CVD. SUBJECTS were breast cancer screening participants in the PROSPECT-EPIC cohort, which is 1 of the 2 Dutch contributions to the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: Each participant completed a validated food frequency questionnaire. Folate intake was calculated with the Dutch National Food Database. Betaine and choline intakes were calculated with the USDA database containing choline and betaine contents of common US foods. Data on coronary heart disease (CHD) events and cerebrovascular accident (CVA) events morbidity data were obtained from the Dutch Centre for Health Care Information., Results: During a median follow-up period of 97 months, 717 women were diagnosed with CVD. After adjustment, neither folate, nor betaine, nor choline intakes were associated with CVD (hazard ratios for highest versus lowest quartile were 1.23 (95% confidence interval 0.75; 2.01), 0.90 (0.69; 1.17), 1.04 (0.71; 1.53), respectively). In a subsample of the population, high folate and choline intakes were statistically significantly associated with lower homocysteine levels. High betaine intake was associated with slightly lower high-density lipoprotein (HDL)-cholesterol concentrations., Conclusion: Regular dietary intakes of folate, betaine and choline were not associated with CVD risk in post-menopausal Dutch women. However, the effect of doses of betaine and choline beyond regular dietary intake--for example, via supplementation or fortification--remains unknown.

Objectives: We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers. As yet, it remains uncertain whether a high concentration of homocysteine itself or whether a low folate status--its main determinant--is involved in the pathogenesis of cardiovascular disease. To shed light on this issue, we performed this study., Design: This was a randomized, placebo-controlled, double-blind, crossover study., Setting: The study was performed at Wageningen University in Wageningen, the Netherlands., Participants: Participants were 39 apparently healthy men and women, aged 50-70 y., Interventions: Participants ingested 0.8 mg/d of folic acid, 6 g/d of betaine, and placebo for 6 wk each, with 6-wk washout in between., Outcome Measures: At the end of each supplementation period, plasma homocysteine concentrations and flow-mediated dilation (FMD) of the brachial artery were measured in duplicate., Results: Folic acid supplementation lowered fasting homocysteine by 20% (-2.0 micromol/l, 95% confidence interval [CI]: -2.3; -1.6), and betaine supplementation lowered fasting plasma homocysteine by 12% (-1.2 micromol/l; -1.6; -0.8) relative to placebo. Mean (+/- SD) FMD after placebo supplementation was 2.8 (+/- 1.8) FMD%. Supplementation with betaine or folic acid did not affect FMD relative to placebo; differences relative to placebo were -0.4 FMD% (95%CI, -1.2; 0.4) and -0.1 FMD% (-0.9; 0.7), respectively., Conclusions: Folic acid and betaine supplementation both did not improve vascular function in healthy volunteers, despite evident homocysteine lowering. This is in agreement with other studies in healthy participants, the majority of which also fail to find improved vascular function upon folic acid treatment. However, homocysteine or folate might of course affect cardiovascular disease risk through other mechanisms.

Objectives: We investigated whether reducing post-methionine homocysteine concentrations via various treatments other than folic acid affects vascular function, as measured through flow-mediated dilation (FMD) of the brachial artery. High fasting and post-methionine homocysteine concentrations are associated with cardiovascular disease risk, but homocysteine might be a surrogate marker for low folate status., Design: This was a randomized, placebo-controlled, double-blind, crossover study., Setting: The study took place at Wageningen University in Wageningen in the Netherlands., Participants: Participants were 39 apparently healthy men and women, aged 50-70 y., Interventions: Participants ingested 10 mg of folic acid, 3 g of betaine, 5 g of serine, and placebo together with an oral methionine load. Each supplement was tested on two different days., Outcome Measures: On each of the eight treatment days, plasma homocysteine concentrations and FMD were measured before (t = 0 h, fasting) and 6 h (t = 6 h) after methionine loading., Results: The mean (+/- SD) fasting homocysteine concentrations averaged over the eight test days were 9.6 +/- 2.1 micromol/l. Mean fasting FMD was 3.1 +/- 2.4 FMD%. A methionine load with placebo increased homocysteine concentrations by 17.2 +/- 9.3 micromol/l at 6 h after loading, similar to the increase following methionine loading with folic acid. A methionine load together with betaine and with serine increased homocysteine by 10.4 +/- 2.8 micromol/l (p < 0.001 relative to placebo) and by 12.1 +/- 8.2 micromol/l (p < 0.001 relative to placebo), respectively. Methionine loading with placebo did not affect FMD, and neither did methionine loading with folic acid, betaine, or serine; differences relative to placebo were +0.7 FMD% (95%CI, -0.6; 1.9), +0.2 FMD% (-1.0; 1.3), and +0.3 FMD% (-0.8; 1.4), respectively., Conclusions: Experimentally induced acute changes in homocysteine concentrations did not affect FMD in healthy volunteers. This implies that potential adverse effects of high homocysteine concentrations on the cardiovascular system are not mediated through vascular function. However, homocysteine or folate may affect cardiovascular disease risk through other mechanisms.

Background: Betaine (trimethylglycine) lowers plasma homocysteine, a possible risk factor for cardiovascular disease. However, studies in renal patients and in obese individuals who are on a weight-loss diet suggest that betaine supplementation raises blood cholesterol; data in healthy individuals are lacking. Such an effect on cholesterol would counteract any favourable effect on homocysteine. We therefore investigated the effect of betaine, of its precursor choline in the form of phosphatidylcholine, and of the classical homocysteine-lowering vitamin folic acid on blood lipid concentrations in healthy humans., Methods and Findings: We measured blood lipids in four placebo-controlled, randomised intervention studies that examined the effect of betaine (three studies, n = 151), folic acid (two studies, n = 75), and phosphatidylcholine (one study, n = 26) on plasma homocysteine concentrations. We combined blood lipid data from the individual studies and calculated a weighted mean change in blood lipid concentrations relative to placebo. Betaine supplementation (6 g/d) for 6 wk increased blood LDL cholesterol concentrations by 0.36 mmol/l (95% confidence interval: 0.25-0.46), and triacylglycerol concentrations by 0.14 mmol/l (0.04-0.23) relative to placebo. The ratio of total to HDL cholesterol increased by 0.23 (0.14-0.32). Concentrations of HDL cholesterol were not affected. Doses of betaine lower than 6 g/d also raised LDL cholesterol, but these changes were not statistically significant. Further, the effect of betaine on LDL cholesterol was already evident after 2 wk of intervention. Phosphatidylcholine supplementation (providing approximately 2.6 g/d of choline) for 2 wk increased triacylglycerol concentrations by 0.14 mmol/l (0.06-0.21), but did not affect cholesterol concentrations. Folic acid supplementation (0.8 mg/d) had no effect on lipid concentrations., Conclusions: Betaine supplementation increased blood LDL cholesterol and triacylglycerol concentrations in healthy humans, which agrees with the limited previous data. The adverse effects on blood lipids may undo the potential benefits for cardiovascular health of betaine supplementation through homocysteine lowering. In our study phosphatidylcholine supplementation slightly increased triacylglycerol concentrations in healthy humans. Previous studies of phosphatidylcholine and blood lipids showed no clear effect. Thus the effect of phosphatidylcholine supplementation on blood lipids remains inconclusive, but is probably not large. Folic acid supplementation does not seem to affect blood lipids and therefore remains the preferred treatment for lowering of blood homocysteine concentrations.