Dietary Intervention Trial Research Articles

DOP097 Emulsifier restriction is an effective therapy for active Crohn’s disease: the ADDapt trial - a multi-centre, randomised, double-blind, placebo-controlled, re-supplementation trial in 154 patients

Abstract Background Food additive emulsifiers result in bacterial dysbiosis, reduced intestinal mucus thickness, microbiota encroachment and increased permeability resulting in intestinal inflammation in murine models. Dietary intervention trials in inflammatory bowel disease are limited by challenges with blinding, high placebo response rates and because changes to one diet component impact on intake of many others (dietary collinearity). The ADDapt trial aimed to investigate the effects of a low emulsifier diet (LED) compared to control diet for 8-weeks on disease activity in patients with mild/moderately active Crohn’s disease (CD). Methods ADDapt (NCT04046913) was an appropriately powered, randomised, double-blind, placebo-controlled, re-supplementation trial (n=154). Patients with a CD activity index (CDAI) of 150-250 plus objective evidence of inflammation (faecal calprotectin (FCP) ≥150 µg/g or endoscopy/radiology) were randomised to either LED (intervention) or LED plus emulsifier re-supplementation (control). Dietary counselling was provided by a dietitian, plus dietary resources and a mobile app to support shopping. To recreate habitual emulsifier intake in controls, both groups received supermarket deliveries for 25% of foods either containing no emulsifiers (intervention) or similar foods containing emulsifiers (control) and were provided three snacks per day that were either emulsifier-free (intervention) or contained carrageenan, carboxymethylcellulose and polysorbate-80 (control). The primary endpoint was the proportion of patients achieving CDAI response (≥70 reduction) at 8-weeks. Secondary endpoints included CDAI remission and FCP. Regression analyses (adjusting for confounders) assessed the difference between trial arms. Results Patients (n=154, ITT population) were recruited from 19 UK centres with 113 (73%) completing the 8-week trial (PP population). Emulsifier intake reduced from median 30.0 (IQR 33.0) to 2.5 (6.0) in the LED group (p<0.001). In the ITT analysis, the primary outcome of CDAI response was achieved in 39 (49.4%) on LED versus 23 (30.7%) in the control group (p=0.019), with an adjusted relative risk (RR) of response of 3.1 (95% CI 1.5, 6.6, p=0.003), a finding that persisted in the PP analysis. In the ITT analysis, compared to control, patients on a LED were more than twice as likely to experience CDAI remission (Adjusted RR 2.1; 95% CI 1.0, 4.4; p=0.042) and >50% reduction in FCP (Adjusted RR 2.9; 95% CI 1.1, 8.0; p=0.039) (Table 1). There were no serious adverse events. Conclusion A LED is an effective treatment in mild/moderately active CD. Ongoing mechanistic analyses will investigate the impact of the LED on gut microbiota and permeability. Funding The Leona M. and Harry B. Helmsley Charitable Trust

FC26 The MEditerranean Diet and Time-Restricted Eating Dietary Interventions for Psoriasis (METRED-P) study: an interim analysis of the first UK-based diet intervention trial

Abstract There is no dietary guidance for people living with psoriasis in the UK, and evidence from randomized controlled trials (RCTs) is lacking. To address the knowledge gap on the efficacy of anti-inflammatory interventions such as the Mediterranean diet (MD) and Time-Restricted Eating (TRE), the MEditerranean Diet and Time-Restricted Eating Dietary interventions for Psoriasis (METRED-P) study aimed to examine the feasibility and collect pilot data subject to an MD, MD with TRE, or a TRE diet on psoriasis severity, life quality, and body composition. The METRED-P study (NCT05820698) was a single-centre parallel-arm feasibility pilot trial recruiting participants between June 2023 and July 2024. Inclusion criteria consisted of a psoriasis area and severity index (PASI) >5, body mass index (BMI) of 20–40 kg/m2, no systemic treatments (or on stable systemic treatments >6 months), and no underlying conditions. Participants were randomized by variance minimization to a TRE diet (10-h eating with 14-h fasting), an MD (rich in fruits, vegetables, whole-grains, fish, olive oil, and nuts) or an MD with TRE, and attended clinic visits at baseline and 12 weeks for repeat measures. Psoriasis severity was assessed with the PASI, life quality with the Dermatology Life Quality Index (DLQI), and body composition with the Tanita® scale. Twenty-four participants (60% female and 40% male) enrolled in the METRED-P study, and 10 participants completed the study to date. Participants reported a mean (SD) age of 44 (10) years, BMI of 28 (6) kg/m2, and baseline PASI of 10 (4). One-way analysis of variance showed statistically significant mean changes in total body fat % and in DLQI scores (P < 0.05). Post hoc analyses showed TRE improved DLQI scores compared with the MD, −11 (4) points, P < 0.05. TRE resulted in the greatest mean reductions in PASI −5 (4), compared with the MD −2 (3) and MD with TRE −1 (3), but statistical significance was not reached in this interim analysis. This is the first study clinically testing the MD and TRE in people with psoriasis. Whilst the METRED-P study is anticipated to end in October 2024, interim analyses illustrate favourable effects of TRE on life quality; an often-overlooked patient outcome. Given the ease and low cost of administration, TRE could be a consideration for people living with psoriasis. These pilot data will enable sample size calculations for fully powered RCTs to confirm these preliminary findings.

Asparagus officinalis L. extract exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells and a transgenic mouse model of endometrial cancer.

Endometrial cancer is the most common malignancy of the female reproductive system in the United States. Asparagus officinalis is a versatile, nutrient-dense, low-calorie vegetable that contains various bioactive metabolites that have shown a variety of biologic functions beneficial to health. The metabolites from asparagus officinalis extracts or asparagus officinalis extracts exhibit significant anti-tumorigenic activity in some pre-clinical models of cancer. Endometrial cancer cells were used to study the effects of asparagus officinalis on anti-proliferation, anti-invasion and increased sensitivity to cisplatin, and obese and lean Lkb1 fl/fl p53 fl/fl mouse model of endometrial cancer was used to study the role of asparagus officinalis in tumor growth. Treatment with increasing concentrations of Asparagus officinalis extracts significantly inhibited cell proliferation, reduced glycolytic activity, induced cellular stress and apoptosis, caused cell cycle G1 arrest, increased the sensitivity of cells to cisplatin, reduced cell adhesion and invasion, and activation of AMPK and inhibition of the AKT/mTOR and MAPK signaling pathways in endometrial cancer cells. Moreover, asparagus officinalis extracts suppressed cell adhesion and invasion through the modulation of the epithelial-to-mesenchymal transition process. Asparagus officinalis extract treatment for 4weeks resulted in a significant reduction in tumor growth in Lkb1 fl/fl p53 fl/fl mice under both obese and lean conditions, with a decrease in Ki-67 and vascular endothelial growth factor expression and an increase in Bip expression in endometrial tumors. These findings provide strong preclinical evidence for the potential therapeutic benefit of asparagus officinalis extract as a novel dietary strategy in the treatment of endometrial cancer. Further clinical trials of dietary intervention of asparagus officinalis or combination with cisplatin in patients with endometrial cancer are warranted.

Diets to promote healthy brain ageing.

Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes. In this Review, we summarize the currently available evidence from observational epidemiology and clinical trials regarding the potential role of diet in theprevention of cognitive decline and dementia. We further discuss possible methodological limitations that might have hindered the ability of previous diet intervention trials to capture potential neuroprotective effects. Considering the overwhelming and continuously expanding societal, economic and health-care burden of Alzheimer disease and other dementias, future nutritional research must address past methodological challenges to accurately and reliably inform clinical practice guidelines and public health policies. Within this scope, we provide a roadmap for future diet intervention trials for dementia prevention. We discuss study designs involving both intensive personalized interventions - to evaluate pharmacokinetic and pharmacodynamic properties, establish neuroprotective thresholds, and test hypothesized biological mechanisms and effects on brain health and cognition through sensitive and precise biomarker measures - and large-scale, pragmatic public health interventions to study population-level benefits.

Higher frequency of fruit and vegetable consumption is associated with greater daily stool weight in adults with constipation

This abstract was presented as the Nutrition in the Treatment, Management and Prevention of Disease Theme Highlight.Chronic constipation is a prevalent gastrointestinal condition affecting approximately 10% of the global population(1) and is associated with substantial healthcare costs and quality of life impairments in the UK(2). While the aetiology of chronic constipation is not fully understood, lower dietary fibre intake is associated with greater risk of constipation(3) and consumption of fruits, vegetables, and wholegrains is recommended within clinical guidelines. Although not diagnostic for constipation, low stool weight is a common feature and is associated with greater risk of colorectal cancer(4); yet few studies have ever measured stool weight in constipation. This study investigated associations between frequency of plant food intake and stool weight in people with constipation.Baseline data from a dietary intervention trial were analysed, which included participants meeting Rome IV criteria for constipation. Self-reported data on habitual consumption of nine plant food categories were collected using a validated tool. Participants performed 7-day total stool collection, which was weighed on the same weighing scales at the research centre. Associations between intake frequency for each plant food category and daily stool weight (total stool weight divided by 7 days) were analysed using independent-samples t-tests (SPSS, version 28, p<0.05 considered significant).Ninety-nine people with Rome IV constipation (89% female; mean [ ± SD] age 32.4 [ ± 12.4] y; BMI 23.0 [ ± 3.2] kg/m2) provided 7-day total stool collections. Mean ( ± SD) stool weight was 72.5 ± 47.2 g/day (minimum 2.1 g/day; maximum 280.6 g/day). Stool weight was significantly higher among those consuming fruit once or more per day (86.2 ± 48.2 g/day), compared with those consuming fruit less than once per day (62.4 ± 44.1 g/day; p = 0.012). Stool weight was also higher among those consuming vegetables once or more per day (98.6 ± 59.1 g/day) compared with those eating vegetables less than once per day (62.2 ± 37.2 g/day; p<0.001). Differences for green salad (79.6 ± 52.1 g/day; 63.3 ± 38.5 g/day; p = 0.088) and high-fibre breads (84.1 ± 46.6 g/day; 65.1 ± 46.6 g/day; p = 0.05) were borderline significant, when comparing those consuming these more than once per week, compared with once or less per week (respectively). No significant differences were found for frequency of consuming fruit juices, potatoes, vegetable soups/stews, high-fibre cereals, or beans and lentils.This is the most comprehensive analysis to date of measured stool weight in constipation, and its association with plant food intake. Despite presence of constipation, participants with higher intakes of fruit and vegetables had a greater daily stool weight; an important feature associated with lower colorectal cancer risk(4). However, intakes were not sufficient to manage their constipation symptoms. Intervention studies investigating potential benefits from increasing fruit and vegetable intakes in people with constipation are required and are currently underway.

Abstract B143: Associations between the food environment and food insecurity on fruit and vegetable intake among urban-dwelling Latina breast cancer survivors participating in the Mi Vida Saludable trial

Abstract Socioeconomic disparities prevalent in Hispanic populations may cause inequities in cancer outcomes and risk factors. We explored the association of access to healthy foods (AHF) and food insecurity (FI) with changes in fruit and vegetable (FV) intake in Latina breast cancer (BC) survivors living in New York City who participated in the Mi Vida Saludable trial. Mi Vida Saludable was a 2x2 factorial trial (n=167) that tested the effects of an in-person and/or eHealth intervention on FV intake and physical activity (PA). Main study results showed only the in-person intervention had modest increases in FV intake. Eligibility criteria included being female, self-identifying as Latina/Hispanic, ³18 years old, history of stage 0-III BC, >3 months post-treatment, <5 daily serving of FV and/or <150 minutes/week of moderate-vigorous PA. FV intake was assessed via 3 24-hour diet recalls at baseline and 12 months. AHF was from a modified validated Access to Healthy Food scale. FI was assessed via questions about eating less or going hungry due to lack of money. Generalized estimating equations examined whether baseline AHF and FI were associated with change in daily FV intake, adjusting for baseline age, marital status, education, and study arm. Three-way interaction terms (AHF or FI with time and study arm) were included to test if associations of AHF and FI with change in FV intake varied by intervention arms. FV intake was log-transformed due to a non-normal distribution; percent changes from baseline were described. AHF was measured in 86 women with 58% and 42% reporting low-medium and high access, respectively. Women with high AHF were more likely to be older (59 vs. 53 years, p=.002) and scored lower on a 5-point acculturation scale (higher score suggests higher acculturation, 1.8 vs. 2.1, p=.01). FI, measured in 157 participant, was prevalent in 23% of women. Women with FI were more likely to be single (44% vs. 16%, p=.003), renting (100% vs. 86%, p=.02), and have higher mean BMI (31 vs. 29 kg/m2, p=.02). 3-way interactions were not statistically significant, though analyses were likely underpowered. In the control group, the adjusted daily FV intake decreased by 79% (p=.01) from baseline to 12 months for women with low-medium AHF and by 49% (p=.10) for those with high AHF; similarly, daily FV intake decreased by 64% (p=.01) for women with FI and by 58% (p=.01) for women without FI. Most Latina BC survivors in New York City who participated in a 12-month diet and PA intervention trial had low-medium AHF at baseline; nearly 1/4 had FI. Associations of AHF or FI with changes in FV intake did not vary significantly by study arm, although sample sizes across strata were small. In the control arm, women with low-medium AHF and FI had larger decreases in FV intake after 12 months. Future dietary intervention studies in Latina BC survivors, and other underserved or under-resourced populations, should account for AHF and FI in the study design, and develop strategies to connect people to healthy food resources. Citation Format: Zachary O. Kadro, Eileen Rillamas-Sun, Blake Langley, Pam Koch, Isobel Contento, Ann Ogden Gaffney, Allison Meisner, Heather Greenlee. Associations between the food environment and food insecurity on fruit and vegetable intake among urban-dwelling Latina breast cancer survivors participating in the Mi Vida Saludable trial [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B143.

The Effect of Individual Attitude toward Healthy Nutrition on Adherence to a High-UFA and High-Protein Diet: Results of a Randomized Controlled Trial.

502 subjects were randomized to an intervention group (IG; dietary pattern focused on high intake of unsaturated fatty acids (UFA), plant protein and fiber) or control group (CG; dietary recommendation in accordance with the German Society of Nutrition) within a 36-month dietary intervention trial. Sum scores for effectiveness, appreciation and practice of healthy nutrition were assessed using ATHN questionnaire during the trial (n = 344). Linear regression models were used to investigate associations between ATHN and dietary patterns at baseline and at month 12. Retirement, higher education level, age and lower body mass index (BMI) were associated with higher ATHN sum scores. ATHN was similar in CG and IG. Higher baseline intake of polyunsaturated fatty acids (PUFA) and fiber as well as lower intake in saturated fatty acids (SFA) were associated with higher scores in practice in both groups. The intervention resulted in a stronger increase of UFA, protein and fiber in the IG after 12 months, while intake of SFA declined (p < 0.01). Higher scores in appreciation were significantly associated with higher intake of fiber and lower intake of SFA in the CG at month 12, whereas no associations between ATHN and macronutrient intake were observed in the IG after 12 months. While ATHN appeared to play a role in general dietary behavior, ATHN did not affect the success of the specific dietary intervention in the IG at month 12. Thus, the dietary intervention achieved a substantial modification of dietary pattern in the IG and was effective to override the impact of the individual ATHN on dietary behavior.

O88 REDUCTION IN SYSTOLIC BLOOD PRESSURE FOLLOWING DIETARY FIBRE INTERVENTION IS DEPENDENT ON BASELINE GUT MICROBIOTA COMPOSITION

Background/Objective: Dietary interventions high in fibre have been shown to lower blood pressure (BP). This effect is via the gut microbiota, via fermentation of fibre and production of metabolites called short-chain fatty acids (SCFAs). Not all patients respond to dietary fibre interventions for unclear reasons. We aimed to determine if we can identify fibre-responders based on their gut microbiota and production of SCFAs. Methods: We performed a phase II cross-over placebo-controlled randomised clinical trial in untreated hypertensive patients. Twenty treatment-naive participants with hypertension received 40 g per day of fermentable fibre delivered as acetylated and butyrylated high amylose maize starch (HAMSAB) or the placebo for 3 weeks. Blood pressure was monitored at baseline and endpoint by ambulatory BP monitoring, with those experiencing a reduction of ≥2 mmHg in systolic BP classified as responders. The microbiota was determined by sequencing the V4-V5 region of the 16S rRNA gene in baseline stool samples. The relationship between baseline gut microbiota and response to dietary intervention was assessed with the MaAsLin2 package. Plasma SCFAs levels were quantified by mass spectrometry. Results: We observed a placebo-subtracted mean 24-hour systolic BP of –6.1 mmHg (p=0.03, reported in Jama et al., 2023 Nature Cardiovascular Research), with 14 (70%) individuals classified as responders and 6 (30%) as non-responders. Genera significantly enriched in responders included Dialister (β=1.29, q=1.921x10-134), Coprococcus (β=1.26, q=3.282x10-121), Bifidobacterium (β=1.67, q=1.11x10-81), Ruminococcus (β=0.161, q=1.11x10-8), and Roseburia (β=0.82, q=4.275x10-2). Responders also produced higher levels of the SCFAs butyrate (mean±SEM, non-responders 4.95±2.4 vs responders 51.15±14.7, p=0.0096), but no difference in other SCFAs. Conclusions: Participants who experienced a decrease in systolic BP following a dietary fibre intervention had increased bacterial genera known to contain species that produce SCFAs (Bifidobacterium, Roseburia, Ruminococcus) at baseline, and were able to produce more butyrate. These data suggest that baseline microbiota composition contributes to the response to dietary fibre intervention trials in people with hypertension, likely via increased capacity to produce butyrate.

The human fecal endocannabinoidome mediator profile is mainly defined by the fecal microbiota and diet.

The endocannabinoid system and its extension, the endocannabinoidome (eCBome), are involved in numerous biological processes, notably energy homeostasis, across virtually all tissues. While the circulating eCBome mediator profile is associated with dietary intakes and metabolic status, an important knowledge gap resides in the identification of the precise determinants of these mediators in the gut lumen. We aimed at establishing the profile of eCBome mediators in human feces and investigating their association with circulating eCBome mediators, dietary intakes, metabolic status and gut microbiota composition. N-acyl-ethanolamines (NAEs) and 2-monoacyl-glycerols (2-MAGs) were profiled by LC-MS/MS in plasma and feces of a cross-sectional cohort (n = 195) and a short term dietary intervention trials (n = 21) with comprehensive dietary intakes and gut microbiota measures. Six NAEs and seven 2-MAGs were identified in fecal samples, but some, especially omega-3 derived mediators, were undetectable in the majority of samples. Fecal NAEs, and to a lower extent 2-MAGs, were positively albeit weakly correlated with the circulating levels of eCBome mediators. Fecal 2-AG, PEA and DHEA levels were positively associated with visceral adiposity and with some parameters of the metabolic profile. Dietary intakes of foods rich in fibers were associated with lower fecal levels of several eCBome mediators, while intakes of unsaturated fatty acids were associated with fecal 2-OG and 2-LG. Interestingly, gut microbiota diversity and composition were a strong correlate of the fecal eCBome profile. The fecal eCBome profile is associated with gut microbiota composition and dietary intakes, more than with the circulating profile. These results strengthen the hypothesis of an interrelation between the gut microbiome and eCBome signaling involved in the regulation of numerous host biological processes.

Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (−32%; 95% confidence interval (95% CI): −21% to −42%) and type 2 diabetes (−26%; 95% CI: −15% to −35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses’ Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications.

Impact of Chronic Consumption of Herbal Rooibos on Cardiovascular Function in Adults with Cardiovascular Risk.

The prevalence of cardiovascular disease (CVD) has increased in South Africa, emphasizing the importance of prevention strategies. This study used echocardiography to investigate the impact of Rooibos on cardiovascular function in those at risk of CVD. This research aims to contribute to understanding its effects on reducing cardiovascular risk factors. The study design involved a 12-week randomized, parallel, double-blinded, placebo-controlled dietary intervention trial using capsules containing standardized water-soluble extracts of green and traditional fermented Rooibos alongside a placebo control. Echocardiography was incorporated as a diagnostic imaging tool to assess cardiac function in the participant cohort. Aorta (AO) dimensions showed no significant change in any intervention group. Left atrium (LA) reduced in size from 3.832 ± 0.071 cm to 3.675 ± 0.067 cm (P = 0.01). There was no significant change in LA/AO ratio in any intervention group. Interventricular septum diameter in the placebo group decreased from 1.334 ± 0.030 cm to 1.250 ± 0.025 cm (P = 0.002), with no significance in fermented Rooibos, while green Rooibos resulted in a decrease from 1.282 ± 0.036 cm to 1.186 ± 0.029 cm (P = 0.002). Left ventricle posterior wall (LVPW) showed no significant changesin any of the intervention group. The left ventricle mass in the placebo and green Rooibos groups demonstrated no significance changes, while fermented Rooibos caused a decrease from 204.102 ± 7.102 g to 191.394 ± 6.707 g (P = 0.015). The phytochemical bioactive components, such as the polyphenolic antioxidants present in green and fermented Rooibos, improved cardiovascular function. This study confirms the effectiveness of echocardiography as imaging tool for assessing cardiac function in this particular population. Regular Rooibos consumption may offer promising therapeutic benefits for preventing and managing CVD risk.

Impact of the rs822393 Variant on Adiponectin Levels and Metabolic Parameters after Weight Loss Secondary to a High-Fat Hypocaloric Diet with Mediterranean Pattern

Introduction: The effects of the rs822393 variant of ADIPOQ gene on metabolic parameters such as insulin resistance and adiponectin levels following weight loss through dietary intervention are still uncertain. The aim of this study was to evaluate the role of rs822393 of ADIPOQ gene on adiponectin levels and metabolic parameters after weight loss with a high-fat hypocaloric diet with Mediterranean pattern during 12 weeks. Methods: A population of 283 patients with obesity was allocated to a dietary intervention trial with a high-fat hypocaloric diet during 12 weeks. Adiposity and biochemical parameters were determined. rs822393 was assessed with a dominant model analysis (CC vs. CT + TT). Results: These patients had three different genotypes: CC (59.0%), CT (33.6%), and TT (7.4%). The allelic frequencies for C and T were 0.89 and 0.20, respectively. Basal and post-intervention HDL cholesterol, adiponectin levels, and adiponectin/leptin ratio were lower in T-allele than non-T-allele carriers. After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin, HOMA-IR, leptin, total cholesterol, and LDL cholesterol levels improved significantly in both genotype groups. Moreover, HDL cholesterol (CC vs. CT + TT) (delta: 8.9 ± 1.1 mg/dL vs. 1.7 ± 0.8 mg/dL; p = 0.02), serum adiponectin in non-T-allele carriers (43.1 ± 5.9 ng/dL vs. 2.8 ± 3 0.0 ng/dL; p = 0.01), and adiponectin/leptin ratio (1.37 ± 0.1 units vs. 0.17 ± 0.08 units; p = 0.02) improved only in non-T-allele carriers after weight loss. Conclusion: Individuals with obesity and without the T allele of rs822393 experienced improvements in adiponectin levels, adiponectin/leptin ratio, and HDL cholesterol levels after following a high-fat hypocaloric diet with a Mediterranean pattern.

IGF-1 and IGFBP-1 as Possible Predictors of Response to Lifestyle Intervention-Results from Randomized Controlled Trials.

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some individuals do not experience anticipated improvements despite weight loss. Biomarkers to identify such individuals at early stages are lacking. Insulin-like growth factor 1 (IGF- 1) and Insulin-like growth factor binding protein 1(IGFBP-1) were shown to predict T2DM onset in prediabetes. We assessed whether these markers also predict the success of lifestyle interventions, thereby possibly guiding personalized strategies. We analyzed the fasting serum levels of IGF-1, IGFBP-1, and Insulin-like growth factor binding protein 2 (IGFBP-2) in relation to changes in metabolic and anthropometric parameters, including intrahepatic lipids (IHLs) and visceral adipose tissue (VAT) volume, measured by magnetic resonance imaging (MRI), in 345 participants with a high risk for prediabetes (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), and significance was set at p < 0.05. Within the 1-year intervention, overall significant improvements were observed. Stratifying individuals by baseline IGF-1 and IGFBP-1 percentiles revealed significant differences: higher IGF-1 levels were associated with more favorable changes compared to lower levels, especially in VAT and IHL. Lower baseline IGFBP-1 levels were associated with greater improvements, especially in IHL and 2 h glucose. Higher bioactive IGF-1 levels might predict better metabolic outcomes following lifestyle interventions in prediabetes, potentially serving as biomarkers for personalized interventions.

Reduction in systolic blood pressure following dietary fibre intervention is dependent on baseline gut microbiota composition

Uncontrolled hypertension is a primary cause of non-communicable diseases and death globally(1). The gut microbiota plays a role in hypertension and dietary interventions high in fibre have been shown to lower blood pressure (BP)(2). Not all participants respond to dietary fibre interventions, for reasons which are unclear. Here we aimed to identify responders of a high fibre intervention based on their baseline gut microbiome. Twenty treatment-naive participants with hypertension received either placebo or 40g per day of prebiotic acetylated and butyrylated high amylose maize starch (HAMSAB) supplementation for 3 weeks in a phase II randomised cross-over double-blind placebo-controlled trial. Blood pressure was monitored at baseline and each endpoint by 24-hour ambulatory BP monitoring, with those experiencing a reduction between timepoints of ≥ 2 mmHg classified as responders. Baseline stool samples were collected and the V4-V5 region of the 16S gene sequenced. Taxonomy was assigned by reference to the SILVA database. The MaAsLin2 package was used for assessing the relationship between baseline gut microbiota and response to dietary intervention. Overall participants had significant reduction in 24-hour systolic BP (–6.1 mmHg, p = 0.03), with 14 individuals classified as responders and six individuals as non-responders. 13 genera were found to be differentially abundant between responders and non-responders. Genera significantly enriched in responders included Dialister (β = 1.29, q = 1.921x10-134), Coprococcus (β = 1.26, q = 3.282x10-121), Bifidobacterium (β = 1.67, q = 1.11x10-81), Ruminococcus (β = 0.161, q = 1.11x10-8) and Roseburia (β = 0.82, q = 4.275x10-2). Participants who experienced a decrease in systolic BP following a dietary fibre intervention had increased level of bacterial genera known to contain species that produce short-chain fatty acids (e.g. Bifidobacterium, Roseburia and Ruminococcus) at baseline. These data suggest that baseline microbiota composition contributes to the response to dietary fibre intervention trials in people with hypertension.

Adherence and eating experiences differ between participants following a flexitarian or vegetarian diet in a 10-week randomised dietary intervention trial

Flexitarian, vegetarian and vegan diets are increasingly popular, particularly amongst young adults. This is the first randomised dietary intervention to investigate the health, wellbeing, and behavioural implications of consuming a basal vegetarian diet that additionally includes low-to-moderate amounts of red meat compared to one containing plant-based meat alternatives (PBMAs) in young adults (NCT04869163)(1). The objective for the current analysis is to measure adherence to the intervention, nutrition behaviours, and participants’ experience with their allocated dietary group. Eighty healthy young adults participated in this 10-week dietary intervention as household pairs. Household pairs were randomised to receive approximately three serves of beef and lamb meat (average of 390 g total cooked weight per person per week, flexitarian group) or PBMAs (350–400 g, vegetarian group) on top of a basal vegetarian diet. Participants were supported to adopt healthy eating behaviours, and this intervention was developed and implemented using a behaviour change framework(2). Diet adherence (eating allocated meat or PBMA, abstaining from animal-based foods not provided by researchers) was monitored daily, with total scores calculated at the end of the 10-week intervention period. Eating experiences were measured by the Positive Eating Scale and a purpose-designed exit survey, and a food frequency questionnaire measured dietary intake. Analyses used mixed effects modelling taking household clustering into account. The average total adherence score was 91.5 (SD = 9.0) out of a possible 100, with participants in the flexitarian group scoring higher (96.1, SD = 4.6, compared to 86.7, SD = 10.0; p &lt; 0.001). Those receiving meat were generally more satisfied with this allocation compared to those receiving the PBMAs, even though a leading motivation for participants joining the study was an opportunity to try plant-based eating (35% expressed that that interest). Participants in both intervention groups had increased vegetable intake (p &lt; 0.001), and reported more positive eating experiences (p = 0.020) and satisfaction with eating (p = 0.021) at the end of the 10-week intervention relative to baseline values. Behavioural methods to encourage engagement with the trial were successful, as participants demonstrated excellent adherence to the intervention. The flexitarian and vegetarian diets elicited different responses in adherence and eating experience. This holds relevance for the inclusion of red meat and PBMAs in healthy, sustainable dietary patterns beyond this study alone.

Implementing eHealth-based behaviour change support within a nutrition intervention trial improves adherence to study-related behaviours in healthy young adults

Nutrition intervention trials play a key role in informing clinical and dietary guidelines. Within these trials, we need participants to change their behaviours; however, researchers seldom systematically consider how to support participants with these changes, contributing to poor adherence. Here we evaluate how using a behaviour change framework to develop support within a dietary intervention impacts young adults’ adherence to required trial behaviours. In the Protein Diet Satisfaction (PREDITION) trial, 80 young adults were randomised to a flexitarian or vegetarian diet for 10-weeks to investigate the psychological and cardiometabolic effects of moderate lean red meat consumption as part of a balanced diet(1). To understand these outcomes, it was key that participants within the trial (i) ate a healthy, basal vegetarian diet (excluding meat, poultry, and fish not provided by research team) and (ii) reported their dietary intake daily on a smartphone application (required to evaluate intervention compliance). To enhance adherence to these behaviours the Nine Principles framework was used to develop behaviour change support (BCS)(2). Key components of the BCS included access to a dietitian-led Facebook group, text reminders, and food delivery. Effectiveness was measured using the following analyses of the 78 participants who completed the study: pre-post change in targeted dietary habits over time using a subscore of the Healthy Diet Habits Index, adherence score to reporting over 10-weeks, Facebook group engagement, and impact evaluation. Analysis included linear imputation modelling, t-tests, and chi-square analysis. The total Healthy Diet Habits Index subscore out of 16 significantly increased from baseline to week 10 (10.6 ± 2.6 to 11.2 ± 2.6, p = 0.011), demonstrating maintenance of a healthy diet. Overall adherence to reporting was high across the 10 weeks, with the total population mean reporting score 90.4 ± 14.6 out of a possible 100. This strengthens study validity, allowing us to confidently report if participants complied with study requirements of consuming the intervention protein (red meat or plant-based meat alternatives) on top of a basal vegetarian diet. Although relatively low active Facebook engagement was observed (on average &lt;1 ‘react’ per post), most participants agreed the text messages and Facebook groups supported them to adhere to recording (63%) and eating healthily (60%), respectively. This is the first study to provide an example of how a framework can be used to systematically develop, implement, and assess BCS within a nutrition trial. This appears to be a promising way to enhance adherence to study-related behaviours, including the burdensome task of reporting dietary intake. We believe this has great potential to improve research validity and decrease resource waste, not only for the PREDITION trial but in future dietary intervention trials.

The consumption of animal products is associated with plasma levels of alpha-aminoadipic acid (2-AAA)

Background and aimsThe cardiometabolic disease-associated metabolite, alpha-aminoadipic acid (2-AAA) is formed from the breakdown of the essential dietary amino acid lysine. However, it was not known whether elevated plasma levels of 2-AAA are related to dietary nutrient intake. We aimed to determine whether diet is a determinant of circulating 2-AAA in healthy individuals, and whether 2-AAA is altered in response to dietary modification. Methods and resultsWe investigated the association between 2-AAA and dietary nutrient intake in a cross-sectional study of healthy individuals (N = 254). We then performed a randomized cross-over dietary intervention trial to investigate the effect of lysine supplementation (1 week) on 2-AAA in healthy individuals (N = 40). We further assessed the effect of a vegetarian diet on 2-AAA in a short-term (4-day) dietary intervention trial in healthy omnivorous women (N = 35). We found that self-reported dietary intake of animal products, including meat, poultry, and seafood, was associated with higher plasma 2-AAA cross-sectionally (P < 0.0001). Supplementary dietary lysine (5g/day) caused no significant increase in plasma 2-AAA; however, plasma 2-AAA was altered by general dietary modification. Further, plasma 2-AAA was significantly reduced by a short-term vegetarian diet (P = 0.003). ConclusionWe identified associations between plasma 2-AAA and consumption of animal products, which were validated in a vegetarian dietary intervention trial, but not in a trial designed to specifically increase the 2-AAA amino acid precursor lysine. Further studies are warranted to investigate whether implementation of a vegetarian diet improves cardiometabolic risk in individuals with elevated 2-AAA.

Association Between Improved Serum Fatty Acid Profiles and Cognitive Function During a Dietary Intervention Trial in Relapsing-Remitting Multiple Sclerosis.

Cognitive impairment is a common multiple sclerosis (MS)-related symptom that impacts quality of life (QOL). Diet interventions are shown to be beneficial in managing QOL, and the intake of essential fatty acids is linked with improved cognitive function. However, the effect of diets on serum fatty acid profiles and cognitive function is unknown. A previous randomized, parallel-arm trial recruited participants with relapsing-remitting MS (N = 77). Study visits included 4 time points: run-in, baseline, 12 weeks, and 24 weeks. During the run-in phase, participants followed their usual diet and were then randomly assigned to either a modified paleolithic (Wahls) or a low saturated fat (Swank) diet at baseline. Assessments at study visits included cognitive function assessed by Symbol Digit Modalities Test-Oral (SDMT-O) and Perceived Deficits Questionnaire (PDQ), and serum fatty acids, including eicosapentaenoic (EPA), docosahexaenoic (DHA), and arachidonic (ARA) acids. Both groups had significant improvements in all serum fatty acids (P < .01), except for ARA, as well as SDMT-O at 24-weeks (P < .05), total PDQ at 12 and 24 weeks (P < .01) compared with baseline values. The 12-week changes in ω-3 (EPA + DHA) index and EPA serum fatty acids were associated with SDMT-O changes (P ≤ .05); however, the changes in fatty acid levels did not mediate the effect of the diets on SDMT-O or PDQ (P > .05). Both diets led to improvements in serum fatty acid profiles and cognitive function, with associations between the 12-week ω-3 (EPA + DHA) index and EPA changes with SDMT-O.

Changes in bile acid subtypes and improvements in lipid metabolism and atherosclerotic cardiovascular disease risk: the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial

BackgroundDistinct circulating bile acid (BA) subtypes may play roles in regulating lipid homeostasis and atherosclerosis. ObjectivesWe investigated whether changes in circulating BA subtypes induced by weight-loss dietary interventions were associated with improved lipid profiles and atherosclerotic cardiovascular disease (ASCVD) risk estimates. MethodsThis study included adults with overweight or obesity (n = 536) who participated in a randomized weight-loss dietary intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 mo after the weight-loss diet intervention. The ASCVD risk estimates were calculated using the validated equations. ResultsAt baseline, higher concentrations of specific BA subtypes were related to higher concentrations of atherogenic very low-density lipoprotein lipid subtypes and ASCVD risk estimates. Weight-loss diet-induced decreases in primary BAs were related to larger reductions in triglycerides and total cholesterol [every 1 standard deviation (SD) decrease of glycocholate, glycochenodeoxycholate, or taurochenodeoxycholate was related to β (standard error) –3.3 (1.3), –3.4 (1.3), or –3.8 (1.3) mg/dL, respectively; PFDR < 0.05 for all]. Greater decreases in specific secondary BA subtypes were also associated with improved lipid metabolism at 6 mo; there was β –4.0 (1.1) mg/dL per 1-SD decrease of glycoursodeoxycholate (PFDR =0.003) for changes in low-density lipoprotein cholesterol. We found significant interactions (P-interaction < 0.05) between dietary fat intake and changes in BA subtypes on changes in ASCVD risk estimates; decreases in primary and secondary BAs (such as conjugated cholate or deoxycholate) were significantly associated with improved ASCVD risk after consuming a high-fat diet, but not after consuming a low-fat diet. ConclusionsDecreases in distinct BA subtypes were associated with improved lipid profiles and ASCVD risk estimates, highlighting the importance of changes in circulating BA subtypes as significant factors linked to improved lipid metabolism and ASCVD risk estimates in response to weight-loss dietary interventions. Habitual dietary fat intake may modify the associations of changes in BAs with ASCVD risk.This trial was registered at clinicaltrials.gov as NCT00072995

Amino Acids Fueling Fibroblast-Like Synoviocyte Activation and Arthritis By Regulating Chemokine Expression and Leukocyte Migration.

We analyzed the impact of amino acid (AA) availability on the inflammatory response in arthritis. We stimulated rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) with tumor necrosis factor (TNF) in the presence or absence of proteinogenic AAs and measured their response by QuantSeq 3' messenger RNA sequencing, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. Signal transduction events were determined by Western blot. We performed K/BxN serum transfer arthritis in mice receiving a normal and a low-protein diet and analyzed arthritis clinically and histologically. Deprivation of AAs decreased the expression of a specific subset of genes, including the chemokines CXCL10, CCL2, and CCL5 in TNF-stimulated FLSs. Mechanistically, the presence of AAs was required for the TNF-induced activation of an interferon regulatory factor 1 (IRF1)-STAT1 signaling circuit that drives the expression of chemotactic factors. The expression of IRF1 and the IRF1-dependent gene set in FLSs was highly correlated with the presence of inflammatory cells in human RA, emphasizing the important role of this AA-dependent pathway in inflammatory cell recruitment to the synovial tissue. Finally, we show that mice receiving a low-protein diet expressed less IRF1 in the inflamed synovium and consequently developed reduced clinical and histologic signs of arthritis. AA deprivation reduces the severity of arthritis by suppressing the expression of IRF1-STAT1-driven chemokines, which are crucial for leukocyte recruitment to the arthritic joint. Overall, our study provides novel insights into critical determinants of inflammatory arthritis and may pave the way for dietary intervention trials in RA.