Performance of Urinary Phenyl-γ-Valerolactones as Biomarkers of Dietary Flavan-3-ol Exposure.

BACKGROUND: Phenyl-γ-valerolactones (PVLs) have been identified as biomarkers of dietary flavan-3-ol exposure, although their utility requires further characterization. OBJECTIVES: We investigated the performance of a range of PVLs as biomarkers indicative of flavan-3-ol intake. METHODS: We report the results of 2 companion studies: a 5-way randomized crossover trial (RCT) and an observational cross-sectional study. In the RCT (World Health Organization, Universal Trial Number: U1111-1236-7988), 16 healthy participants consumed flavan-3-ol-rich interventions (of apple, cocoa, black tea, green tea, or water [control]) for 1 d each. First morning void samples and 24-h urine samples were collected with diet standardized throughout. For each participant, 1 intervention period was extended (to 2 d) to monitor PVL kinetics after repeat exposure. In the cross-sectional study, 86 healthy participants collected 24-h urine samples, and concurrent weighed food diaries from which flavan-3-ol consumption was estimated using Phenol-Explorer. A panel of 10 urinary PVLs was quantified using liquid chromatography tandem mass spectrometry. RESULTS: In both studies, 2 urinary PVLs [5-(3'-hydroxyphenyl)-γ-valerolactone-4'-sulfate and putatively identified 5-(4'-hydroxyphenyl)-γ-valerolactone-3'-glucuronide] were the principal compounds excreted (>75%). In the RCT, the sum of these PVLs was significantly higher than the water (control) after each intervention; individually, there was a shift from sulfation toward glucuronidation as the total excretion of PVLs increased across the different interventions. In the extended RCT intervention period, no accumulation of these PVLs was observed after consecutive days of treatment, and after withdrawal of treatment on the third day, there was a return toward negligible PVL excretion. All results were consistent, whether compounds were measured in 24-h urine or first morning void samples. In the observational study, the sum of the principal PVLs correlated dose dependently (Rs = 0.37; P = 0.0004) with dietary flavan-3-ol intake, with similar associations for each individually. CONCLUSIONS: Urinary 5-(3'-hydroxyphenyl)-γ-valerolactone-4'-sulfate and putatively identified 5-(4'-hydroxyphenyl)-γ-valerolactone-3'-glucuronide are recommended biomarkers for dietary flavan-3-ol exposure.

An examination of primary health care nursing service evaluation using the Donabedian model: A systematic review.

Nurses are key to the delivery of global primary health care services. However, there appears to be a lack of evaluation of primary health care nursing delivery models in the published literature. This evaluation is vital to the improvement of patient experiences, national and global health outcomes, and the justification of future investment in primary health care nursing services. The purpose of this review was to explore and analyze the literature that reports on the evaluation of primary health care nursing services, to ascertain the nature and utility of these evaluation methods, and identify opportunities for future research in this area. A systematic review of the published literature was conducted following PRISMA guidelines, using the databases CINAHL, Joanna Briggs Institute, MEDLINE, and Proquest. Thirty-two articles published between 2010 and 2022 were selected. Results were organized using the Donabedian model. A paucity of research into the evaluation of nurse-led primary health care services was noted. Where evident, evaluation of primary health care nursing services tended to reflect the medical model. Medical outcomes measures dominated evaluation criteria including diagnosis rates, prescription costs, and disease outcomes. Primary health care principles such as service accessibility, cultural appropriateness, and availability were rarely used. The perspectives and experiences of nurses were not sought in service evaluation, including most of the nurse-led services. Development of an evidence-base of nursing primary health care services that are informed by the nursing experience and apply a framework of universal primary health care principles across the structure, process, and outcomes aspects of the service is recommended.

Limitations with the Digestible Indispensable Amino Acid Score (DIAAS) with Special Attention to Plant-Based Diets: a Review.

PURPOSE OF REVIEW: This review describes several limitations of the Digestible Indispensable Amino Acid Score (DIAAS) with a focus on its application to plant-based dietary patterns. RECENT FINDINGS: Evaluating protein quality in terms of digestibility is paramount to support and optimize the health and well-being of human populations in situations where food insecurity and protein energy malnutrition are widespread. The Food and Agriculture Organization (FAO) of the United Nations has endorsed the DIAAS to replace the previously recommended Protein Digestibility Corrected Amino Acid Score (PDCAAS) for protein quality assessment. While multiple strengths characterize the DIAAS, substantial limitations remain, many of which are accentuated in the context of a plant-based dietary pattern. Some of these limitations include a failure to translate differences in nitrogen-to-protein conversion factors between plant- and animal-based foods, limited representation of commonly consumed plant-based foods within the scoring framework, inadequate recognition of the increased digestibility of commonly consumed heat-treated and processed plant-based foods, its formulation centered on fast-growing animal models rather than humans, and a focus on individual isolated foods vs the food matrix. The DIAAS is also increasingly being used out of context where its application could produce erroneous results such as exercise settings. When investigating protein quality, particularly in a plant-based dietary context, the DIAAS should ideally be avoided.

Does Fibre-fix provided to people with irritable bowel syndrome who are consuming a low FODMAP diet improve their gut health, gut microbiome, sleep and mental health? A double-blinded, randomised controlled trial.

INTRODUCTION: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) is an effective way to reduce gut symptoms in people with irritable bowel syndrome (IBS). This diet reduces the intake of fermentable fibres, leading to changes of the gut microbiota and insufficient fermentation in the large bowel, resulting in reduced production of short-chain fatty acids (SCFAs), such as butyrate, which has unfavourable implications for gut health, sleep and mental health. This study will examine the effect of Fibre-fix, a supplement containing a mix of dietary fibres, on the human gut microbiome composition, fermentative capacity, sleep, quality of life (QOL) and mental health of people with IBS who consume a low FODMAP diet (LFD). METHODS AND ANALYSIS: A randomised, double-blind, placebo-controlled, study design is proposed to examine whether Fibre-fix added to an existing LFD may help modulate gastrointestinal function, improve markers of sleep, mental health and promote QOL in patients with IBS. Participants will provide stool and blood samples, daily bowel symptoms diaries and 3-day diet records. Additionally, they will complete validated questionnaires relating to FODMAP intake, sleep, mental health and QOL before and after a 3-week intervention. Gut health will be assessed via faecal microbiome composition, faecal pH and SCFA levels. Alteration of sleep will be recorded using an actigraphy device worn by all participants over the whole study. Multivariate analysis will be used to examine the gut microbiome and repeated measures Analysis of variance (ANOVA) will be used for dependent variables from questionnaires related to bowel symptoms, stool type, sleep, mental health and QOL to assess the differences between intervention and control groups after adjustment for confounding variables. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Human Research Ethics Committee of Edith Cowan University (2019-00619-YAN). Results will be disseminated in peer-review journal publications, and conference presentations. Participants will be provided with a summary of findings once the study is completed. If Fibre-fix is shown to result in favourable changes in gut microbial composition, SCFA production, sleep and mental well-being without exacerbating symptoms, this will provide additional dietary management options for those with IBS following an LFD. TRIAL REGISTRATION NUMBER: ACTRN12620000032954.

Limitations of the Digestible Indispensable Amino Acid Score (DIAAS) and Choice of Statistical Reporting. Comment on "A Comparison of Dietary Protein Digestibility, Based on DIAAS Scoring, in Vegetarian and Non-Vegetarian Athletes. Nutrients 2019, 11, 3106".

Dear Editor, [...].

Long-term Paleolithic diet is associated with lower resistant starch intake, different gut microbiota composition and increased serum TMAO concentrations.

BACKGROUND: The Paleolithic diet is promoted worldwide for improved gut health. However, there is little evidence available to support these claims, with existing literature examining anthropometric and cardiometabolic outcomes. OBJECTIVE: To determine the association between dietary intake, markers of colonic health, microbiota, and serum trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with cardiovascular disease. DESIGN: In a cross-sectional design, long-term (n = 44, > 1 year) self-reported followers of a Paleolithic diet (PD) and controls (n = 47) consuming a diet typical of national recommendations were recruited. Diets were assessed via 3-day weighed diet records; 48-h stool for short chain fatty acids using GC/MS, microbial composition via 16S rRNA sequencing of the V4 region using Illumina MiSeq. TMAO was quantified using LC-MS/MS. RESULTS: Participants were grouped according to PD adherence; namely excluding grains and dairy products. Strict Paleolithic (SP) (n = 22) and Pseudo-Paleolithic (PP) (n = 22) groups were formed. General linear modelling with age, gender, energy intake and body fat percentage as covariates assessed differences between groups. Intake of resistant starch was lower in both Paleolithic groups, compared to controls [2.62, 1.26 vs 4.48 g/day (P < 0.05)]; PERMANOVA analysis showed differences in microbiota composition (P < 0.05), with higher abundance of TMA-producer Hungatella in both Paleolithic groups (P < 0.001). TMAO was higher in SP compared to PP and control (P < 0.01), and inversely associated with whole grain intake (r = - 0.34, P < 0.01). CONCLUSIONS: Although the PD is promoted for improved gut health, results indicate long-term adherence is associated with different gut microbiota and increased TMAO. A variety of fiber components, including whole grain sources may be required to maintain gut and cardiovascular health. CLINICAL TRIAL REGISTRATIONS: Australian and New Zealand Clinical Trial Registry (ANZCTRN12616001703493).

A Paleolithic diet lowers resistant starch intake but does not affect serum trimethylamine-N-oxide concentrations in healthy women.

The Paleolithic diet excludes two major sources of fibre, grains and legumes. However, it is not known whether this results in changes to resistant starch (RS) consumption. Serum trimethylamine-N-oxide (TMAO) is produced mainly from colonic fermentation and hepatic conversion of animal protein and is implicated in CVD, but changes in RS intake may alter concentrations. We aimed to determine whether intake of RS and serum concentrations of TMAO varied in response to either the Paleolithic or the Australian Guide to Healthy Eating (AGHE) diets and whether this was related to changes in food group consumption. A total of thirty-nine women (mean age 47 (sd 13) years, BMI 27 (sd 4) kg/m2) were randomised to AGHE (n 17) or Paleolithic diets (n 22) for 4 weeks. Serum TMAO concentrations were measured using liquid chromatography-MS; food groups, fibre and RS intake were estimated from weighed food records. The change in TMAO concentrations between groups (Paleolithic 3·39 µm v. AGHE 1·19 µm, P = 0·654) did not reach significance despite greater red meat and egg consumption in the Paleolithic group (0·65 serves/d; 95 % CI 0·2, 1·1; P <0·01, and 0·22 serves/d; 95 % CI 0·1, 0·4, P <0·05, respectively). RS intake was significantly lower on the Paleolithic diet (P <0·01) and was not associated with TMAO concentrations. However, the limited data for RS and the small sample size may have influenced these findings. While there were no significant changes in TMAO concentrations, increased meat consumption and reduced RS intake warrant further research to examine the markers of gastrointestinal health of Paleolithic diet followers and to update Australian food databases to include additional fibre components.

Development and validation of a simple LC-MS/MS method for the simultaneous quantitative determination of trimethylamine-N-oxide and branched chain amino acids in human serum.

Serum branched chain amino acids and trimethylamine-N-oxide are monitored as potential indicators of diabetes and cardiovascular health respectively. A rapid method for their simultaneous determination using liquid chromatography and tandem mass spectrometry is described here. Branched chain amino acids and trimethylamine-N-oxide were quantified based on their specific MS/MS fragments using a selected reaction monitoring approach. A number of columns were tested for their ability to separate the analytes. A C18-PFP column separated the analytes in just 4 minutes, and resulted in excellent peak shape and retention time repeatability, and was therefore chosen as the optimal column. A second column, the Intrada Amino Acid column, was chosen for comparison and validation experiments as it provided an orthogonal separation mechanism. The intra-day and inter-day precision and accuracy were less than 12% for trimethylamine-N-oxide and less than 6% for the branched chain amino acids. Recoveries, where serum was spiked with three different concentrations of the analytes, ranged from 97 to 113%. The LODs and LOQs for trimethylamine-N-oxide were 1 and 6 ng/mL, for leucine and isoleucine were 4 and 8 ng/mL, and for valine were 5 and 15 ng/mL, respectively. The C18-PFP column method was validated using the Intrada Amino Acid column method and percentage agreement for all four analytes was within 10%. Sample preparation was minimal, and use of labelled internal standards accounted for matrix effects. The method was successfully applied to human plasma samples. Graphical abstract ᅟ.

Compliance, Palatability and Feasibility of PALEOLITHIC and Australian Guide to Healthy Eating Diets in Healthy Women: A 4-Week Dietary Intervention.

(1) BACKGROUND/OBJECTIVES: The Paleolithic diet has been receiving media coverage in Australia and claims to improve overall health. The diet removes grains and dairy, whilst encouraging consumption of fruits, vegetables, meat, eggs and nuts. Our aim was to compare the diet to the Australian Guide to Healthy Eating (AGHE) in terms of compliance, palatability and feasibility; (2) SUBJECTS/METHODS: 39 healthy women (age 47 ± 13 years, BMI 27 ± 4 kg/m²) were randomised to an ad-libitum Paleolithic (n = 22) or AGHE diet (n = 17) for 4-weeks. A food checklist was completed daily, with mean discretionary consumption (serves/day) calculated to assess compliance. A 12-item questionnaire was administered post intervention to assess palatability and feasibility; (3) RESULTS: The AGHE group reported greater daily consumption of discretionary items (1.0 + 0.6 vs. 0.57 + 0.6 serves/day, p = 0.03). Compared to the AGHE group, the Paleolithic group reported a significantly greater number of events of diarrhoea (23%, 0%, p = 0.046), costs associated with grocery shopping (69%, 6% p < 0.01) and belief that the diet was not healthy (43%, 0% p < 0.01); (4) CONCLUSIONS: Compliance to both diets was high but the potential side effects and increased cost suggest that the Paleolithic diet may not be practical in clinical/public health settings. Further studies are required to assess longer term feasibility.

Cardiovascular, Metabolic Effects and Dietary Composition of Ad-Libitum Paleolithic vs. Australian Guide to Healthy Eating Diets: A 4-Week Randomised Trial.

(1) BACKGROUND: The Paleolithic diet is popular in Australia, however, limited literature surrounds the dietary pattern. Our primary aim was to compare the Paleolithic diet with the Australian Guide to Healthy Eating (AGHE) in terms of anthropometric, metabolic and cardiovascular risk factors, with a secondary aim to examine the macro and micronutrient composition of both dietary patterns; (2) METHODS: 39 healthy women (mean ± SD age 47 ± 13 years, BMI 27 ± 4 kg/m²) were randomised to either the Paleolithic (n = 22) or AGHE diet (n = 17) for four weeks. Three-day weighed food records, body composition and biochemistry data were collected pre and post intervention; (3) RESULTS: Significantly greater weight loss occurred in the Paleolithic group (-1.99 kg, 95% CI -2.9, -1.0), p < 0.001). There were no differences in cardiovascular and metabolic markers between groups. The Paleolithic group had lower intakes of carbohydrate (-14.63% of energy (E), 95% CI -19.5, -9.7), sodium (-1055 mg/day, 95% CI -1593, -518), calcium (-292 mg/day 95% CI -486.0, -99.0) and iodine (-47.9 µg/day, 95% CI -79.2, -16.5) and higher intakes of fat (9.39% of E, 95% CI 3.7, 15.1) and ß-carotene (6777 µg/day 95% CI 2144, 11410) (all p < 0.01); (4) CONCLUSIONS: The Paleolithic diet induced greater changes in body composition over the short-term intervention, however, larger studies are recommended to assess the impact of the Paleolithic vs. AGHE diets on metabolic and cardiovascular risk factors in healthy populations.