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Abstract: Dietary components, like β-glucans, can modulate the intestinal immune response. We previously showed that fecal water enriched with oat β-glucan stimulated the cytokine-induced immune response of enterocytes. It is, however, unclear whether β-glucans activate nuclear factor-κB (NF-κB) pathways in the intestine in vivo and if so, whether enterocytes, intestinal leukocytes, or both respond to β-glucans. We evaluated the effects of an oral gavage of 3 mg dietary oat (1→3), (1→4)-β-d-glucans that was administered twice daily during 3.5 days on intestinal NF-κB transactivation and subsequent cytokine production of intestinal leukocytes and enterocytes in 16 NF-κB reporter mice. We hypothesized that oat β-glucan activates the central immune transcription factor NF-κB and increased cytokine secretion, as we previously reported immune stimulating effects by oat β-glucan. We found that mice that were administered oat β-glucans (n = 8) showed an increased intestinal NF-κB transactivation in leukocytes (P = .021) and enterocytes (P = .012), particularly in the proximal part of the small intestine (ileum), as compared to placebo mice (n = 8). Surprisingly, NF-κB was not activated in the colon. Furthermore, the level of interleukin 12 was increased in intestinal lysates from all compartments, whereas the concentration of interferon γ was decreased in the proximal small intestine (P = .046). Finally, tumor necrosis factor α showed a trend toward a reduced production in the colon (P = .057). Because we have earlier shown that human enterocyte cell lines do not express the β-glucan receptor dectin-1 in vitro, we now conclude that after consumption, dietary oat β-glucans most likely firstly activate the intestinal leukocytes, which in turn increases cellular activation of enterocytes. [Copyright &y& Elsevier]

We evaluated the effects of 2 commonly available strategies (plant stanol ester drink and 10 mg simvastatin) on coronary heart disease (CHD) risk variables in participants with metabolic syndrome. Metabolic syndrome patients are at increased risk to develop CHD, partly due to high triacylglycerol (TAG) and low HDL cholesterol (HDL-C) concentrations and a low-grade inflammatory profile. Effects of plant stanol esters on TAG concentrations in these participants are unknown. After a 3-wk run-in period in which individuals consumed placebo yogurt drinks and placebo capsules, participants were randomly divided into 4 groups: placebo (n = 9), simvastatin + placebo drink (n = 10), placebo + stanol drink (n = 9), and simvastatin + stanol drink (n = 8). After 9 wk, we evaluated the effects on serum lipids, low-grade inflammation, and endothelial dysfunction markers. In metabolic syndrome patients, stanol esters (2.0 g/d), simvastatin, or the combination lowered non-HDL-C by 12.8% (P = 0.011), 30.7% (P < 0.001), and 35.4% (P < 0.001), respectively, compared with placebo. TAG were lowered by 27.5% (P = 0.044), 21.7% (P = 0.034), and 32.7% (P < 0.01), respectively. The total-:HDL-C ratio was significantly lowered in all 3 intervention groups. We found no treatment effects on the apolipoprotein CII:CIII ratio, cholesterol ester transfer protein mass, FFA concentrations, and markers for low-grade inflammation or endothelial dysfunction. This study shows that in metabolic syndrome patients, plant stanol esters lower not only non-HDL-C, but also TAG. Effects on TAG were also present in combination with statin treatment, illustrating an additional benefit of stanol esters in this CHD risk population. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human in vivo data on dietary determinants of alpha-linolenic acid (ALA; 18:3n-3) metabolism are scarce. OBJECTIVE: We examined whether intakes of ALA or linoleic acid (LA; 18:2n-6) or their ratio influences ALA metabolism. DESIGN: During 4 wk, 29 subjects received a control diet (7% of energy from LA, 0.4% of energy from ALA, ALA-to-LA ratio = 1:19). For the next 6 wk, a control diet, a low-LA diet (3% of energy from LA, 0.4% of energy from ALA, ratio = 1:7), or a high-ALA diet (7% of energy from LA, 1.1% of energy from ALA, ratio = 1:7) was consumed. Ten days before the end of each dietary period, [U-(13)C]ALA was administered orally for 9 d. ALA oxidation was determined from breath. Conversion was estimated by using compartmental modeling of [(13)C]- and [(12)C]n-3 fatty acid concentrations in fasting plasma phospholipids. RESULTS: Compared with the control group, ALA incorporation into phospholipids increased by 3.6% in the low-LA group (P = 0.012) and decreased by 8.0% in the high-ALA group (P < 0.001). In absolute amounts, it increased by 34.3 mg (P = 0.020) in the low-LA group but hardly changed in the high-ALA group. Nearly all ALA from the plasma phospholipid pool was converted into eicosapentaenoic acid. Conversion of eicosapentaenoic acid into docosapentaenoic acid and docosahexaenoic acid hardly changed in the 3 groups and was <0.1% of dietary ALA. In absolute amounts, it was unchanged in the low-LA group, but increased from 0.7 to 1.9 mg (P = 0.001) in the high-ALA group. ALA oxidation was unchanged by the dietary interventions. CONCLUSION: The amounts of ALA and LA in the diet, but not their ratio, determine ALA conversion. Copyright © 2006 American Society for Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: beta-Glucan can reduce serum concentrations of total and LDL cholesterol. The mechanism of this action is not clear, however, and it is difficult to predict the cholesterol-lowering effect of a food product enriched with beta-glucan. OBJECTIVES: We examined the effects of a beta-glucan-enriched fruit juice on serum lipids and lipoproteins and on markers of cholesterol absorption (serum concentrations of plant sterols) and synthesis (serum concentrations of lathosterol). In addition, we measured effects on lipid-soluble antioxidants. DESIGN: After a 3-wk run-in period, healthy subjects consumed daily a fruit drink providing 5 g rice starch [placebo (control) group; n = 22] or beta-glucan from oats (n = 25) for 5 wk (parallel design). At the end of the run-in period and at the end of the intervention, blood samples were taken for analysis of lipids and lipoproteins, noncholesterol sterols, and fat-soluble antioxidants. Changes between the end of the run-in period and the end of the intervention were calculated for each subject. Differences in changes between the groups were analyzed statistically. RESULTS: The differences between the control and beta-glucan groups in the change in serum concentrations of total and LDL cholesterol, respectively, were -4.8% (P = 0.012) and -7.7% (P = 0.005). The differences between the groups in the change in serum concentrations of lathosterol and sitosterol were -13% (P = 0.023) and -11% (P = 0.030), respectively. No significant effects were found on fat-soluble antioxidants. CONCLUSIONS: Beta-glucan lowers serum concentrations of total and LDL cholesterol when incorporated into a fruit drink. A reduced cholesterol absorption contributes to the cholesterol-lowering effect of beta-glucan without affecting plasma concentrations of lipid-soluble antioxidants. Copyright © 2006 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have suggested that oleic and stearic acids, as well as oleic and linoleic acids, have comparable effects on the serum lipoprotein profile. If so, then substituting these three 18-carbon fatty acids for each other would result in similar effects on the serum lipoprotein profile. OBJECTIVE: The aim of this study was to compare simultaneously the effects of stearic, oleic, and linoleic acids on the serum lipoprotein profile of healthy subjects. DESIGN: Forty-five subjects (27 women and 18 men) consumed in random order 3 experimental diets, each for 5 wk. The diets provided 38% of energy from fat, of which 60% was supplied by the experimental fats. The dietary compositions of the diets were the same, except for 7% of energy, which was provided by stearic, oleic, or linoleic acid. At the end of each intervention period, serum lipid and lipoprotein concentrations were measured. In addition, LDL, HDL, and VLDL particle sizes and particle concentrations of lipoprotein subclasses were analyzed by nuclear magnetic resonance spectroscopy. RESULTS: No significant diet-induced changes in serum lipids and lipoproteins were found. Mean (+/-SD) serum LDL-cholesterol concentrations were 3.79 +/- 0.91, 3.71 +/- 0.79, and 3.65 +/- 0.91 mmol/L with the high-stearic acid, high-oleic acid, and high-linoleic acid diets, respectively (P = 0.137 for diet effects). Mean (+/-SD) HDL-cholesterol concentrations were 1.45 +/- 0.43, 1.46 +/- 0.45, and 1.46 +/- 0.44 mmol/L (P = 0.866). LDL, HDL, and VLDL particle sizes and lipoprotein subclass distributions also did not differ significantly between the 3 diets. CONCLUSIONS: With realistic intakes of stearic, oleic, and linoleic acids, differences between their effects on the serum lipoprotein profile are small. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: Findings about the effects of beta-glucan on serum lipoproteins are conflicting. OBJECTIVE: The study investigated the effects of beta-glucan from oat bran in bread and cookies (study 1) and in orange juice (study 2) on serum lipoproteins in mildly hypercholesterolemic subjects. DESIGN: In study 1, 48 subjects (21 men, 27 women) received for 3 wk control bread and cookies rich in wheat fiber. For the next 4 wk, by random assignment, 23 subjects continued to consume the control products, and 25 received bread and cookies rich in beta-glucan. Mean daily intake of beta-glucan was 5.9 g. Total dietary fiber intake did not differ significantly between the groups. In study 2, the same sources of control fiber and beta-glucan (5 g/d) as in study 1 were provided. For 2 wk, 25 of the original 48 subjects (10 men, 15 women) were randomly assigned to consume orange juice containing either wheat fiber (n = 13) or beta-glucan from oat bran (n = 12). After a washout period of 1 wk, dietary regimens were crossed over. RESULTS: In study 1, the change in LDL cholesterol did not differ significantly (-0.12 mmol/L; P = 0.173) between the 2 groups. In study 2, the drink rich in beta-glucan decreased LDL cholesterol by 0.26 +/- 0.07 mmol/L (6.7 +/- 1.8%; P = 0.001) and the ratio of total to HDL cholesterol by 0.26 +/- 0.11 (5.4 +/- 2.1%; P = 0.029) compared with the other drink. HDL-cholesterol and triacylglycerol concentrations did not change significantly. CONCLUSIONS: The food matrix or the food processing, or both, could have adverse effects on the hypocholesterolemic properties of oat beta-glucan. Copyright © 2003 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Until 15-20 years ago, many nutritionists were mainly interested in the effects of diet on health-related variables such as blood pressure and serum cholesterol concentrations. Without doubt, these studies have made an important contribution to our current understanding of the relationship between diet and health. For many reasons, however, few researchers have tried to explain these effects at the molecular level. Nowadays, however, it seems that the picture has been reversed; much research is being directed towards studying the effects of dietary components at the molecular level. This type of research has been made possible by, among other factors, the implementation of techniques from the more fundamental sciences into nutrition research. Also, the availability of genome sequences has accelerated this shift of interest. The aims of these studies are to obtain detailed information on the molecular and metabolic responses of cells and tissues, or even the whole organism, to dietary components. In these studies, also, the interactions between diet and genetic background, and between diet and different physiological and pathological conditions need to be addressed. However, it is not only important to obtain information on mechanisms, but also on the functional consequences for the organism. One ultimate question, however, is whether this information can be used to develop tests that can form the basis of dietary advice for specific subpopulations. These challenging questions can only be tackled through an integrated approach that combines the expertise from various disciplines. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tocotrienols, lipid-soluble antioxidants with vitamin E activity, have been reported to lower LDL-cholesterol concentrations and platelet aggregation in men, but results are contradictory. OBJECTIVE: To examine in detail the effects of a vitamin E concentrate rich in tocotrienols on serum lipoproteins and on platelet function in men at risk for cardiovascular disease. DESIGN: In this randomized, double-blind, placebo-controlled parallel trial, 20 men received daily for 6 wk 4 capsules, each containing 35 mg tocotrienols and 20 mg alpha-tocopherol; 20 other men received 4 capsules daily, each providing 20 mg alpha-tocopherol. All men had concentrations of serum total cholesterol between 6.5 and 8.0 mmol/L or lipoprotein(a) concentrations > 150 mg/L. RESULTS: Compliance was confirmed by changes in serum tocopherol and tocotrienol concentrations. Serum LDL cholesterol in the tocotrienol group was 4.80 mmol/L before and 4.79 mmol/L after intervention, and increased from 4.70 to 4.86 mmol/L in the placebo group (95% CI for the difference: -0.54, 0.19 mmol/L; P = 0.333). Also, changes in HDL cholesterol, triacylglycerol, lipoprotein(a), and lipid peroxide concentrations did not differ between the groups. After adjustment for differences in initial values, no effects were found on collagen-induced platelet aggregation velocity, maximum aggregation, or thromboxane B2 formation in citrated whole blood. ATP release, however, was lower in the tocotrienol group. Urinary thromboxane B2 and 11-keto-thromboxane B2 concentrations and coagulation and fibrinolytic measures did not change. CONCLUSION: The tocotrienol supplements used had no marked favorable effects on the serum lipoprotein profile or on platelet function in men with slightly elevated lipid concentrations. Copyright (c) 1999 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) has a multifactorial aetiology and many potential risk markers are known. As it was not feasible to discuss all markers and their possible interactions in relation to all aspects of CVD, selections had to be made in this paper. In the context of claims and functional foods, emphasis was placed on those aetiological processes and risk markers that have been shown previously to be modified by diet: lipid and lipoprotein metabolism, haemostatic function, oxidative damage, homocysteine metabolism, and blood pressure. Except for methodological and biological characteristics of these biomarkers, their relationships with the risk of CVD are discussed.For LDL and HDL cholesterol, fasting triacylglycerol, homocysteine, and blood pressure well-validated, easy applicable, and generally accepted biomarkers exist. For haemostatic function and oxidative damage validation of markers with respect to CVD or intermediate clinical markers is recommended. For diet-related CVD, however, the ultimate question is whether changes in the biomarker are truly related to changes in risk. Only for LDL cholesterol and blood pressure does consensus exist among scientists for a possible application as enhanced function claims. For HDL, triacylglycerol, and homocysteine, and in particular for haemostatic function and oxidative damage, however, formal proof is lacking that diet-induced changes in these biomarkers alter the risk of CVD. At the same time, it should be emphasised that CVD is multifactorial. Therefore it does not seem justified that a change in one particular biomarker is enough evidence to substantiate a claim. There are examples of food components or drugs that one biomarker is changed in a favourable way, but at the same time another biomarker is changed in an unfavourable way. Therefore, studies to further validate generic predictors for the CVD risk should be initiated. [ABSTRACT FROM AUTHOR]

Purpose: Short-term intake of the egg-protein hydrolysate Newtricious (NWT)-03 improved executive function, but underlying mechanisms and long-term effects, including other cognitive domains, are unknown., Methods: A 36-week randomized controlled trial involving 44 overweight/obese individuals experiencing elevated Subjective Cognitive Failures (SCF; aged 60-75 years) assessed the impact of daily consumption of 5.7 g of NWT-03 or placebo powders on cognitive performance (psychomotor speed, executive function, memory) and Cerebral Blood Flow (CBF), a marker of brain vascular function. Cognitive performance was evaluated using a neurophysiological test battery (CANTAB) and CBF was measured using magnetic resonance imaging perfusion method Arterial Spin Labeling (ASL). Serum samples were collected to determine brain-derived neurotrophic factor (BDNF) concentrations., Results: Anthropometrics, and energy and nutrient intakes remained stable throughout the trial. NWT-03 was well tolerated, and compliance was excellent (median: 99%; range: 87-103%). No overall intervention effects were observed on cognitive performance or CBF, but post-hoc analyses revealed significant improvements on executive function in women, but not men. Specifically, a reduction of 74 ms in reaction latency on the multitasking task (95% CI: -134 to -15; p = 0.02), a reduction of 9 between errors (95%CI: -14 to -3; p < 0.001), and a reduction of 9 total errors (95%CI: -15 to -3; p < 0.001) on the spatial working memory task were found in women. No intervention effects were observed on serum BDNF concentrations (p = 0.31)., Conclusion: Long-term consumption of NWT-03 improved multitasking abilities and working memory in women with elevated SCF. Brain vascular function remained unaffected. Sex differences in executive function require additional clarification., (© 2024. The Author(s).)

Background: People with overweight/obesity generally have impaired immune responses, resulting among others in increased risk of severe complaints and hospitalization after infections with severe acute respiratory syndrome coronavirus 2 (COVID-19), as well as decreased antibody production after vaccinations. Plant stanol ester previously increased the combined IgM/IgG antibody titers toward a hepatitis A vaccination in patients with allergic asthma, but the underlying mechanism is unknown., Objectives: We evaluated whether plant stanol ester consumption improved the immune response in subjects with overweight/obesity after a COVID-19 vaccination., Methods: A double-blind, randomized, placebo-controlled trial was performed. Thirty-two subjects with overweight/obesity consumed products with added plant stanols (4 g/d; provided as plant stanol ester) or control ≥2 wk before receiving their COVID-19 vaccination until 4 wk after vaccination. Antibody titers were analyzed weekly and statistically analyzed using mixed models. Serum metabolic markers and cytokine profiles were also analyzed., Results: IgM concentrations against the COVID-19 Spike protein were increased in the plant stanol ester group compared with the control group, with the largest difference observed 2 wk after vaccination [31.2 (0.43, 62.1) BAU/mL, or +139%; Group × Time: P = 0.031]. Subjects that produced very low IgM antibodies produced, as expected, hardly any IgG antibodies. In those with IgG seroconversion, IgG Spike concentrations were also increased in the plant stanol ester group compared with the control group [71.3 (2.51, 140.1) BAU/mL; Group P = 0.043]. Stimulated cytokine concentrations decreased in the plant stanol ester group compared with the control group in all 3 cytokine domains (that is, proinflammatory, T helper [Th1]/Th17, and Th2/regulatory T cells). Between-group differences in serum LDL cholesterol or other metabolic markers were not observed., Conclusions: Consuming plant stanols (4 g/d) affects immune responses to COVID-19 vaccinations, translating into increased serum anti-COVID-19 IgM concentrations in subjects with overweight/obesity. Only in IgG seroconverted subjects, serum anti-COVID-19 IgG concentrations also increase. These effects are independent of reductions in LDL cholesterol. These results suggest that this high-risk group for COVID-19 complications could benefit from plant stanol consumption. This trial was registered at clinicaltrials.gov as NCT04844346., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Improving brain insulin sensitivity, which can be assessed by measuring regional cerebral blood flow (CBF) responses to intranasal insulin, may prevent age-related metabolic and cognitive diseases., Objectives: This study aimed to investigate longer-term effects of mixed nuts on brain insulin sensitivity in older individuals with overweight/obesity., Methods: In a randomized, single-blinded, controlled, crossover trial, 28 healthy adults (mean ± standard deviation: 65 ± 3 years; body mass index: 27.9 ± 2.3 kg/m 2 ) received either daily 60-g mixed nuts (15 g of walnuts, pistachio, cashew, and hazelnuts) or no nuts (control) for 16 weeks, separated by an 8-week washout period. Throughout the study, participants were instructed to adhere to the Dutch food-based dietary guidelines. During follow-up, brain insulin action was assessed by quantifying acute effects of intranasal insulin on regional CBF using arterial spin labeling magnetic resonance imaging. Furthermore, effects on peripheral insulin sensitivity (oral glucose tolerance test), intrahepatic lipids, and cardiometabolic risk markers were assessed., Results: Body weight and composition did not change. Compared with control, mixed nut consumption improved regional brain insulin action in 5 clusters located in the left (difference in CBF responses to intranasal insulin: -4.5 ± 4.7 mL/100 g/min; P < 0.001; -4.6 ± 4.8 mL/100 g/min; P < 0.001; and -4.3 ± 3.6 mL/100 g/min; P = 0.007) and right occipital lobes (-4.3 ± 5.6 mL/100 g/min; and -3.9 ± 4.9 mL/100 g/min; P = 0.028). A fifth cluster was part of the left frontal lobe (-5.0 ± 4.6 mL/100 g/min; P < 0.001). Peripheral insulin sensitivity was not affected. Intrahepatic lipid content (-0.7%-point; 95% CI: -1.3%-point to -0.1%-point; P = 0.027), serum low-density lipoprotein cholesterol concentration (-0.24 mmol/L; 95% CI: -0.44 to -0.04 mmol/L; P = 0.019), and systolic blood pressure (-5 mm Hg; 95% CI: -8 to -1 mm Hg; P = 0.006) were lower after the mixed nut intervention., Conclusions: Longer-term mixed nut consumption affected insulin action in brain regions involved in the modulation of metabolic and cognitive processes in older adults with overweight/obesity. Intrahepatic lipid content and different cardiometabolic risk markers also improved, but peripheral insulin sensitivity was not affected. This trial was registered at clinicaltrials.gov as NCT04210869., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The interest in intermittent energy restriction (IER) diets as a weight-loss approach is increasing. Different IER protocols exist, including time-restricted eating (TRE), alternate-day fasting (ADF), and the 5:2 diet. This meta-analysis compared the effects of these IER diets with continuous energy restriction (CER) on anthropometrics and cardiometabolic risk markers in healthy adults. Twenty-eight trials were identified that studied TRE (k = 7), ADF (k = 10), or the 5:2 diet (k = 11) for 2-52 wk. Energy intakes between intervention groups within a study were comparable (17 trials), lower in IER (5 trials), or not reported (6 trials). Weighted mean differences (WMDs) were calculated using fixed- or random-effects models. Changes in body weight [WMD: -0.42 kg; 95% confidence interval (CI): -0.96 to 0.13; P = 0.132] and fat mass (FM) (WMD: -0.31 kg; 95% CI: -0.98 to 0.36; P = 0.362) were comparable when results of the 3 IER diets were combined and compared with those of CER. All IER diets combined reduced fat-free mass (WMD: -0.20 kg; 95% CI: -0.39 to -0.01; P = 0.044) and waist circumference (WMD: -0.91 cm; 95% CI: -1.76 to -0.06; P = 0.036) more than CER. Effects on body mass index [BMI (kg/m 2 )], glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), serum lipid and lipoprotein concentrations, and blood pressure did not differ. Further, TRE reduced body weight, FM, and fat-free mass more than CER, whereas ADF improved HOMA-IR more. BMI was reduced less in the 5:2 diet compared with CER. In conclusion, the 3 IER diets combined did not lead to superior improvements in anthropometrics and cardiometabolic risk markers compared with CER diets. Slightly greater reductions were, however, observed in fat-free mass and waist circumference. To what extent differences in energy intakes between groups within studies may have influenced these outcomes should be addressed in future studies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The metabolic syndrome is associated with cardiovascular diseases and cognitive decline. The egg protein hydrolysate NWT-03 has shown to improve cardiovascular risk factors in humans. This study investigated whether NWT-03 also has an effect on cognitive function. Methods: Men and women with the metabolic syndrome ( n  = 76) with a mean age of 60 ± 10 years participated in this randomized, double-blind, placebo-controlled, cross-over trial with an intervention (5 g/day NWT-03) and control period (5 g/day maltodextrin) of 4 weeks separated by a wash-out period of 2-8 weeks. Cognitive function was assessed with the anti-cue reaction time test (impulse control) and psychomotor vigilance test (sustained attention) at day 0, 2, and 27 of both periods. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured at the start and end of both periods. Results: NWT-03 consumption significantly improved the change (day 27 - day 0) in response times of the anti-cue reaction time test compared with the control period ( P  < 0.001), but not of the psychomotor vigilance test ( P  = 0.487). Serum BDNF concentrations of all subjects did not significantly change ( P  = 0.241). Conclusion: NWT-03 has the ability to improve cognitive function within the executive function domain. The underlying mechanism warrants further research and could either be indirect via inhibition of dipeptidyl peptidase 4 (DPP4) or direct via passage of small peptides over the blood-brain barrier inducing local effects. Trial registration: ClinicalTrials.gov identifier: NCT02561663.

Background: Short-term intake of egg-derived protein hydrolysates, such as NWT-03, suggest improvements in arterial stiffness and metabolic profiles, but longer-term trials are lacking. This study therefore examined the longer-term effects of NWT-03 on arterial stiffness and cardiometabolic markers in men and women with metabolic syndrome., Methods: Seventy-six adults with metabolic syndrome (age 61 ± 10 years; BMI 31.7 ± 4.0 kg/m 2 ) participated in a randomized, controlled, double-blind, cross-over trial with a 27-day intervention (5 g/day NWT-03) or placebo period, separated by two-to-eight weeks of washout. At the start and end of both periods, measurements were performed in the fasting state and 2 h following acute NWT-03 intake. Arterial stiffness was assessed by carotid-to-radial (PWV c-r ), carotid-to-femoral pulse wave velocity (PWV c-f ), and central augmentation index (CAIxHR75). Moreover, cardiometabolic markers were assessed., Results: Compared with control, longer-term NWT-03 supplementation did not affect fasting PWV c-r (0.1 m/s; -0.2 to 0.3; P = 0.715) or PWV c-f (-0.2 m/s; -0.5 to 0.1; P = 0.216). Fasting pulse pressure (PP) was however reduced by 2 mmHg (95% CI: -4 to 0; P = 0.043), but other fasting cardiometabolic markers were not affected. No effects were observed following acute NWT-03 intake at baseline. However, acute intake of NWT-03 after the intervention significantly lowered CAIxHR75 (-1.3%-point; -2.6 to -0.1; P = 0.037) and diastolic BP (-2 mmHg; -3 to 0; P = 0.036), but other cardiometabolic markers did not change., Conclusion: Longer-term NWT-03 supplementation did not affect arterial stiffness, but modestly improved fasting PP in adults with metabolic syndrome. Acute intake of NWT-03 after the intervention also improved CAIxHR75 and diastolic BP., Trial Registration: The study was registered at ClinicalTrials.gov as NCT02561663., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Findings concerning the effects of almond consumption on glucose metabolism are inconsistent which might relate to body weight gain. The effects of long-term almond consumption on glucose metabolism are investigated in a free-living setting without detailed dietary instructions in males and females with overweight/obesity and prediabetes., Methods: Forty-three participants volunteered in this randomized, cross-over trial with a 5-months control and intervention period and a 2-months wash-out. In the intervention period participants daily consumed 50 g whole almonds. At the end of both periods insulin sensitivity was assessed by a hyperinsulinemic euglycemic clamp, and postprandial glucose responses, and 48 h continuous glucose concentrations were measured., Results: Almond consumption significantly decreased insulin sensitivity (P = 0.002), and increased postprandial glucose concentrations (P = 0.019), as well as fasting insulin concentrations (P = 0.003) as compared to the control period. The AUCs for 24 h glucose concentrations were not significantly different between control and intervention (P = 0.066). Almond consumption also significantly increased BMI (P = 0.002), and waist circumference (P = 0.013), supported by the concurrent increased energy intake (P = 0.031). The effects on glucose metabolism could only partly be explained by the observed weight gain as the almond effect remained after correcting for BMI changes., Conclusions: In participants with prediabetes, long-term almond consumption showed adverse effects on insulin sensitivity and glucose metabolism. As almonds seemed not to have fully replaced other food items, it might be necessary to provide more supporting guidelines on how to incorporate energy-dense nuts into healthy diets to prevent type 2 diabetes development., Clinical Trial Registration: This clinical trial was registered in February 2018 as NCT03419702., (© 2023. The Author(s).)

Background: Nut consumption may reduce age-related cognitive decline, but underlying mechanisms are unclear., Objective: To investigate in older adults longer-term effects of mixed nut consumption on brain vascular function, which may underlie improvements in cognitive performance., Methods: Twenty-eight healthy individuals (age [mean ± SD]: 65 ± 3 years; BMI: 27.9 ± 2.3 kg/m 2 ) were included in a randomized, single-blinded, cross-over trial with a 16-week intervention (60 g/d mixed nuts: walnuts, pistachio, cashew, and hazelnuts) and control period (no nuts), separated by 8 weeks of washout. Participants followed the Dutch food-based dietary guidelines. At the end of each period, cerebral blood flow (CBF), a marker of brain vascular function, was quantified using arterial spin labeling magnetic resonance imaging. Effects on endothelial function, arterial stiffness, and the retinal microvasculature were also assessed. Cognitive performance was measured using the Cambridge Neuropsychological Test Automated Battery., Results: Body weight remained stable during the study. As compared to the control period, the mixed nut intervention resulted in a higher regional CBF in the right frontal and parietal lobes (treatment effect: 5.0 ± 6.5 mL/100 g/min; P < 0.001), left frontal lobe (5.4 ± 7.1 mL/100 g/min; P < 0.001), and bilateral prefrontal cortex (5.6 ± 6.6 mL/100 g/min; P < 0.001). Carotid artery reactivity (0.7 PP; 95%CI: 0.2 to 1.2; P = 0.007), brachial flow-mediated vasodilation (1.6 PP; 95%CI: 1.0 to 2.2; P < 0.001) and retinal arteriolar calibers were higher (2 μm; 95%CI: 0 to 3; P = 0.037), and carotid-to-femoral pulse wave velocity lower (-0.6 m/s; 95%CI: -1.1 to -0.1; P = 0.032). Further, visuospatial memory (-4 errors [16%]; 95%CI: -8 to 0; P = 0.045) and verbal memory (+1 correct [16%]; 0 to 2; P = 0.035) improved, but executive function and psychomotor speed did not change., Conclusions: Longer-term mixed nut consumption as part of a healthy diet beneficially affected brain vascular function, which may relate to the observed beneficial effects on memory in older adults. Moreover, different characteristics of the peripheral vascular tree also improved., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Single nucleotide polymorphisms (SNPs) in circadian clock relevant genes are associated with several metabolic health variables, but little is known about their associations with human cholesterol metabolism. Therefore, this study examined associations between SNPs in ARNTL, ARNTL2, CLOCK, CRY1, CRY2, PER2, and PER3 with the intestinal cholesterol absorption markers campesterol and sitosterol, the endogenous cholesterol synthesis marker lathosterol, and total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in 456 healthy individuals from Western European descent. One SNP in ARNTL2 (rs1037924) showed a significant association with lathosterol. Several SNPs in ARNTL (rs4146388, rs58901760, rs6486121), ARNTL2 (rs73075788), CLOCK (rs13113518, rs35115774, rs6832769), and CRY1 (rs2078074) were significantly associated with intestinal cholesterol absorption. Genetic variants in CRY2, PER2, and PER3 were not significantly associated with intestinal cholesterol absorption or endogenous cholesterol synthesis. None of the SNPs were associated with TC or LDL-C, except for one SNP in PER2 (rs11894491) with serum LDL-C concentrations. The findings suggest that various SNPs in ARNTL, ARNTL2, CLOCK and CRY1 play a role in intestinal cholesterol absorption and endogenous cholesterol synthesis, which was not reflected in TC and LDL-C concentrations. The significant associations between SNPs and intestinal cholesterol absorption and endogenous cholesterol synthesis should be validated in other cohorts., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)