Background: We assessed the bioavailability of orange juice (poly)phenols by monitoring urinary flavanone metabolites and ring fission catabolites produced by the action of the colonic ...microbiota.Objective: Our objective was to identify and quantify metabolites and catabolites excreted in urine 0–24 h after the acute ingestion of a (poly)phenol-rich orange juice by 12 volunteers.Design: Twelve volunteers 6 men and 6 women; body mass index (in kg/m2): 23.9–37.2 consumed a low (poly)phenol diet for 2 d before first drinking 250 mL pulp-enriched orange juice, which contained 584 μmol (poly)phenols of which 537 μmol were flavanones, and after a 2-wk washout, the procedure was repeated, and a placebo drink was consumed. Urine collected for a 24-h period was analyzed qualitatively and quantitatively by using high-performance liquid chromatography–mass spectrometry (HPLC-MS) and gas chromatography–mass spectrometry (GC-MS).Results: A total of 14 metabolites were identified and quantified in urine by using HPLC-MS after orange juice intake. Hesperetin-O-glucuronides, naringenin-O-glucuronides, and hesperetin-3′-O-sulfate were the main metabolites. The overall urinary excretion of flavanone metabolites corresponded to 16% of the intake of 584 μmol (poly)phenols. The GC-MS analysis revealed that 8 urinary catabolites were also excreted in significantly higher quantities after orange juice consumption. These catabolites were 3-(3′-methoxy-4′-hydroxyphenyl)propionic acid, 3-(3′-hydroxy-4′-methoxyphenyl)propionic acid, 3-(3′-hydroxy-4′-methoxyphenyl)hydracrylic acid, 3-(3′-hydroxyphenyl)hydracrylic acid, 3′-methoxy-4′-hydroxyphenylacetic acid, hippuric acid, 3′-hydroxyhippuric acid, and 4′-hydroxyhippuric acid. These aromatic acids originated from the colonic microbiota-mediated breakdown of orange juice (poly)phenols and were excreted in amounts equivalent to 88% of (poly)phenol intake. When combined with the 16% excretion of metabolites, this percentage raised the overall urinary excretion to ∼100% of intake.Conclusions: When colon-derived phenolic catabolites are included with flavanone glucuronide and sulfate metabolites, orange juice (poly)phenols are much-more bioavailable than previously envisaged. In vitro and ex vivo studies on mechanisms underlying the potential protective effects of orange juice consumption should use in vivo metabolites and catabolites detected in this investigation at physiologic concentrations. The trial was registered at BioMed Central Ltd (www.controlledtrials.com) as ISRCTN04271658.
Aims/hypothesis
High-throughput metabolomics technologies in a variety of study designs have demonstrated a consistent metabolomic signature of overweight and type 2 diabetes. However, the extent to ...which these metabolomic patterns can be reversed with weight loss and diabetes remission has been weakly investigated. We aimed to characterise the metabolomic consequences of a weight-loss intervention in individuals with type 2 diabetes.
Methods
We analysed 574 fasted serum samples collected within an existing RCT (the Diabetes Remission Clinical Trial DiRECT) (
N
=298). In the trial, participating primary care practices were randomly assigned (1:1) to provide either a weight management programme (intervention) or best-practice care by guidelines (control) treatment to individuals with type 2 diabetes. Here, metabolomics analysis was performed on samples collected at baseline and 12 months using both untargeted MS and targeted
1
H-NMR spectroscopy. Multivariable regression models were fitted to evaluate the effect of the intervention on metabolite levels.
Results
Decreases in branched-chain amino acids, sugars and LDL triglycerides, and increases in sphingolipids, plasmalogens and metabolites related to fatty acid metabolism were associated with the intervention (Holm-corrected
p
<0.05). In individuals who lost more than 9 kg between baseline and 12 months, those who achieved diabetes remission saw greater reductions in glucose, fructose and mannose, compared with those who did not achieve remission.
Conclusions/interpretation
We have characterised the metabolomic effects of an integrated weight management programme previously shown to deliver weight loss and diabetes remission. A large proportion of the metabolome appears to be modifiable. Patterns of change were largely and strikingly opposite to perturbances previously documented with the development of type 2 diabetes.
Data availability
The data used for analysis are available on a research data repository (
https://researchdata.gla.ac.uk/
) with access given to researchers subject to appropriate data sharing agreements. Metabolite data preparation, data pre-processing, statistical analyses and figure generation were performed in R Studio v.1.0.143 using R v.4.0.2. The R code for this study has been made publicly available on GitHub at:
https://github.com/lauracorbin/metabolomics_of_direct
.
Graphical Abstract
The effect of roasting of coffee beans and the extraction of ground coffee with different volumes of hot pressurised water on the caffeine and the total caffeoylquinic acids (CQAs) content of the ...resultant beverages was investigated. While caffeine was stable higher roasting temperatures resulted in a loss of CQAs so that the caffeine/CQA ratio was a good marker of the degree of roasting. The caffeine and CQA content and volume was determined for 104 espresso coffees obtained from coffee shops in Scotland, Italy and Spain, limited numbers of cappuccino coffees from commercial outlets and several instant coffees. The caffeine content ranged from 48-317 mg per serving and CQAs from 6-188 mg. It is evident that the ingestion of 200 mg of caffeine per day can be readily and unwittingly exceeded by regular coffee drinkers. This is the upper limit of caffeine intake from all sources recommended by US and UK health agencies for pregnant women. In view of the variable volume of serving sizes, it is also clear that the term "one cup of coffee" is not a reproducible measurement for consumption, yet it is the prevailing unit used in epidemiology to assess coffee consumption and to link the potential effects of the beverage and its components on the outcome of diseases. More accurate measurement of the intake of coffee and its potentially bioactive components are required if epidemiological studies are to produce more reliable information.
Diabetes management relies on effective evidence-based advice that informs and empowers individuals to manage their health. Alongside other cornerstones of diabetes management, dietary advice has the ...potential to improve glycaemic levels, reduce risk of diabetes complications and improve health-related quality of life. We have updated the 2004 recommendations for the nutritional management of diabetes to provide health professionals with evidence-based guidelines to inform discussions with patients on diabetes management, including type 2 diabetes prevention and remission. To provide this update we commissioned new systematic reviews and meta-analyses on key topics, and drew on the broader evidence available. We have strengthened and expanded on the previous recommendations to include advice relating to dietary patterns, environmental sustainability, food processing, patient support and remission of type 2 diabetes. We have used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to determine the certainty of evidence for each recommendation based on findings from the commissioned and identified systematic reviews. Our findings indicate that a range of foods and dietary patterns are suitable for diabetes management, with key recommendations for people with diabetes being largely similar for those for the general population. Important messages are to consume minimally processed plant foods, such as whole grains, vegetables, whole fruit, legumes, nuts, seeds and non-hydrogenated non-tropical vegetable oils, while minimising the consumption of red and processed meats, sodium, sugar-sweetened beverages and refined grains. The updated recommendations reflect the current evidence base and, if adhered to, will improve patient outcomes.
Graphical abstract
The Diabetes Remission Clinical Trial reported return and persistence of non-diabetic blood glucose control in 46% of people with type 2 diabetes of up to 6 years duration. Detailed metabolic studies ...were performed on a subgroup (intervention, n = 64; control, n = 26). In the intervention group, liver fat content decreased (16.0% ± 1.3% to 3.1% ± 0.5%, p < 0.0001) immediately after weight loss. Similarly, plasma triglyceride and pancreas fat content decreased whether or not glucose control normalized. Recovery of first-phase insulin response (0.04−0.05–0.32 to 0.110.0005–0.51 nmol/min/m2, p < 0.0001) defined those who returned to non-diabetic glucose control and this was durable at 12 months (0.110.005–0.81 nmol/min/m2, p = 0.0001). Responders were similar to non-responders at baseline but had shorter diabetes duration (2.7 ± 0.3 versus 3.8 ± 0.4 years; p = 0.02). This study demonstrates that β cell ability to recover long-term function persists after diagnosis, changing the previous paradigm of irreversible loss of β cell function in type 2 diabetes.
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•Substantial weight loss can reverse the processes underlying type 2 diabetes•Liver fat content is normalized and pancreas fat content decreased in all•Return to non-diabetic glucose control depends upon β cell ability to recover
Type 2 diabetes has long been regarded as lifelong and progressive. Taylor et al. demonstrate that weight loss of over 10 kg results in normalization of ectopic fat within liver and pancreas. This is associated with durable recovery of β cell function and non-diabetic glucose control in the majority.
Context:
Low testosterone (T) has been associated with incident metabolic syndrome (MetS), but it remains unclear if this association is independent of sex hormone binding globulin (SHBG). Estradiol ...(E2) may also be associated with MetS, but few studies have investigated this.
Objective:
To study the association between baseline sex steroids and the development of incident MetS and to investigate the influence of SHBG, body mass index (BMI) and insulin resistance on this risk.
Methods:
Three thousand three hundred sixty nine community-dwelling men aged 40–79 years were recruited for participation in EMAS. MetS was defined by the updated NCEP ATP III criteria. Testosterone and E2 levels were measured by liquid and gas chromatography/mass spectrometry, respectively. Logistic regression was used to assess the association between sex steroids and incident MetS.
Results:
One thousand six hundred fifty one men without MetS at baseline were identified. During follow-up, 289 men developed incident MetS, while 1362 men did not develop MetS. Men with lower baseline total T levels were at higher risk for developing MetS odds ratio (OR) = 1.72, P < .001), even after adjustment for SHBG (OR = 1.43, P = .001), BMI (OR = 1.44, P < .001) or homeostasis model assessment of insulin resistance (HOMA-IR) (OR = 1.64, P < .001). E2 was not associated with development of MetS (OR = 1.04; P = .56). However, a lower E2/T ratio was associated with a lower risk of incident MetS (OR = 0.38; P < .001), even after adjustment for SHBG (OR = 0.48; P < .001), BMI (OR = 0.60; P = .001) or HOMA-IR (OR = 0.41; P < .001).
Conclusions:
In men, lower T levels, but not E2, are linked with an increased risk of developing MetS, independent of SHBG, BMI or insulin resistance. A lower E2/T ratio may be protective against developing MetS.
To explore the factors (including knowledge and attitude) influencing the decision to follow a low-carbohydrate diet (LCD) or not in a sample of the UK population. An online questionnaire was ...distributed electronically to adults who had either followed LCD or not (February-December 2019). Demographics and self-reported "LCD-status" (current, past and non-follower) were collected. Multivariable linear regression was used with carbohydrate knowledge, dietary guideline agreement and theory of planned behaviour (TPB) constructs (all as predictors) to explain the intention to follow a LCD (outcome). Respondents (n = 723, 71% women, median age 34; 85% white-ethnicity) were either following (n = 170, 24%) or had tried a LCD in the preceding 3 months (n = 184, 25%). Current followers had lower carbohydrate knowledge scores (1-2 point difference, scale - 11 to 11) than past and non-followers. A majority of current LCD followers disagreed with the EatWell guide recommendations "Base meals on potatoes, bread, rice and pasta, or other starchy carbohydrates. Choose whole grains where possible" (84%) and "Choose unsaturated oils and spreads and eat in small amounts such as vegetable, rapeseed, olive and sunflower oils" (68%) compared to past (37%, 10%, respectively) and non-followers (16%, 8%, respectively). Weight-loss ranked first as a motivation, and the internet was the most influencial source of information about LCDs. Among LCD-followers, 71% reported ≥ 5% weight loss, and over 80% did not inform their doctor, nurse, or dietitian about following a diet. Approximately half of LCD followers incorporated supplements to their diets (10% used multivitamin/mineral supplements), despite the restrictive nature of the diet. TPB constructs, carbohydrate knowledge, and guideline agreement explained 60% of the variance for the intention to follow a LCD. Attitude (std-β = 0.60), perceived behavioural control (std-β = 0.24) and subjective norm (std-β = 0.14) were positively associated with the intention to follow a LCD, while higher knowledge of carbohydrate, and agreeing with national dietary guidelines were both inversely associated (std-β = - 0.09 and - 0.13). The strongest primary reason behind UK adults' following a LCD is to lose weight, facilitated by attitude, perceived behavioural control and subjective norm. Higher knowledge about carbohydrate and agreement with dietary guidelines are found among people who do not follow LCDs.
Epidemiological evidence of the beneficial health effects of fish consumption is strong, but the evidence from intervention trials is less documented. Our aim was to evaluate the state of the ...evidence on the potential effects of fish consumption on vascular risk factors arising from intervention trials.
A systematic literature search was undertaken in OVID MEDLINE, Scopus, and EMBASE, which were searched from inception to June 2017. A meta-analysis of intervention trials was performed to estimate the effect of fish consumption on vascular risk factors in adults (age >18 years). Primary outcomes included lipid biomarkers such as triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol, and also novel biomarkers of vascular risk. Secondary outcomes were related to feasibility and acceptability aspects of these interventions. Random-effects models were used to determine the pooled effect sizes.
14 trials, including a total of 1378 individuals, fulfilled the inclusion criteria for this study. Consuming oily fish was associated with significant reductions in plasma triglycerides (−0.11 mmol/L; 95% CI -0.18 to −0.04; p = 0.002). While a significant increase in HDL-cholesterol was observed (0.06 mmol/L, 95% CI 0.02 to −0.11; p = 0.008). No significant effect could be observed on other vascular risk factors.
This study showed that there is evidence indicating that consuming oily fish led to significant improvements in two important biomarkers of cardiovascular risk, such as triglycerides and HDL levels. These results strongly support the important role for oily fish as part of a healthy diet.
•Consuming oily fish is associated with beneficial effects to health.•Current evidence from intervention trials indicates that consuming fish significantly improves some blood lipids, blood pressure and endothelial function.•Fish consumption may potentially reduce the risk of cardiovascular diseases and mortality.•The effects of consuming fish on novel biomarkers of vascular risk needs further investigation.
Context:
Late-onset hypogonadism (LOH) has been defined as a syndrome in middle-aged and elderly men reporting symptoms in the presence of low testosterone (T).
Objective:
The objective of the study ...was to seek objective biochemical and end-organ evidence of androgen deficiency in men classified as having LOH according to our previously published criteria.
Design, Setting, and Participants:
The design of the study included cross-sectional data from the European Male Aging Study on 2966 community-dwelling men aged 40–79 years in eight European countries.
Main Outcome Measure(s):
Waist circumference, body mass index, muscle mass, estimated heel bone mineral density (eBMD), hemoglobin, insulin sensitivity, physical activity, metabolic syndrome, insulin resistance index, and cardiovascular disease were measured.
Results:
Sixty-three men (2.1%) were classified as having LOH: 36 moderate and 27 severe. They were older and more obese than eugonadal men and had, in proportion to the graded T deficiency, lower muscle mass, eBMD, and hemoglobin, with poorer general health. Both moderate and severe LOH was associated with lower hemoglobin, mid-upper arm circumference, eBMD, physical function (measured by the Short Form-36 questionnaire), slower gait speed and poorer general health. Only men with severe LOH showed significant associations with larger waist circumference (β= 1.93cm; 0.04–3.81), insulin resistance (β= 2.81; 1.39–4.23), and the metabolic syndrome (odds ratio 9.94; 2.73–36.22) after adjustments for confounders. Men with low testosterone only (irrespective of symptoms) showed lesser magnitudes of association with the same end points.
Conclusions:
LOH is associated with multiple end-organ deficits compatible with androgen deficiency. These data support the existence of a syndrome of LOH in only a minority of aging men, especially those with T below 8 nmol/liter.
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