Associations of metabolomic profiles with circulating vitamin E and urinary vitamin E metabolites in middle-aged individuals.
Nutrition (Burbank, Los Angeles County, Calif.). 2022;:111440
Vitamin E (α-tocopherol [α-TOH]) is transported in lipoprotein particles in blood, but little is known about the transportation of its oxidized metabolites. In the Netherlands Epidemiology of Obesity Study, we aimed to investigate the associations of 147 circulating metabolomic measures obtained through targeted nuclear magnetic resonance with serum α-TOH and its urinary enzymatic (α-CEHC) and oxidized (α-TLHQ) metabolites from 24-h urine quantified by liquid chromatography with tandem mass spectrometry. Multivariable linear regression analyses, in which multiple testing was taken into account, were performed to assess associations between metabolomic measures (determinants; standardized to mean = 0, SD = 1) and vitamin E metabolites (outcomes), adjusted for demographic factors. We analyzed 474 individuals (55% women, 45% men) with a mean (SD) age of 55.7 (6.0) y. Out of 147 metabolomic measures, 106 were associated (P < 1.34 × 10-3) with serum α-TOH (median β [interquartile range] = 0.416 [0.383-0.466]), predominantly lipoproteins associated with higher α-TOH. The associations of metabolomic measures with urinary α-CEHC have directions similar to those with α-TOH, but effect sizes were smaller and non-significant (median β [interquartile range] = 0.065 [0.047-0.084]). However, associations of metabolomic measures with urinary α-TLHQ were markedly different from those with both serum α-TOH and urinary α-CEHC, with negative and small-to-null relations to most very-low-density lipoproteins and amino acids. Therefore, our results highlight the differences in the lipoproteins involved in the transportation of circulating α-TOH and oxidized vitamin E metabolites. This indicates that circulating α-TOH may be representative of the enzymatic but not the antioxidative function of vitamin E.
Lifestyle risks for chronic disease among Australian adolescents: a cross-sectional survey.
The Medical journal of Australia. 2022;(3):156-157
Association of measures of body fat with serum alpha-tocopherol and its metabolites in middle-aged individuals.
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(8):2407-2415
BACKGROUND AND AIMS The accumulation of fat increases the formation of lipid peroxides, which are partly scavenged by alpha-tocopherol (α-TOH). Here, we aimed to investigate the associations between different measures of (abdominal) fat and levels of urinary α-TOH metabolites in middle-aged individuals. METHODS AND RESULTS In this cross-sectional analysis in the Netherlands Epidemiology of Obesity study (N = 511, 53% women; mean [SD] age of 55 [6.1] years), serum α-TOH and α-TOH metabolites from 24-h urine were measured as alpha-tocopheronolactone hydroquinone (α-TLHQ, oxidized) and alpha-carboxymethyl-hydroxychroman (α-CEHC, enzymatically converted) using liquid-chromatography-tandem mass spectrometry. Body mass index and total body fat were measured, and abdominal subcutaneous and visceral adipose tissue (aSAT and VAT) were assessed using magnetic resonance imaging. Using multivariable-adjusted linear regression analyses, we analysed the associations of BMI, TBF, aSAT and VAT with levels of urinary α-TOH metabolites, adjusted for confounders. We observed no evidence for associations between body fat measures and serum α-TOH. Higher BMI and TBF were associated with lower urinary levels of TLHQ (0.95 [95%CI: 0.90, 1.00] and 0.94 [0.88, 1.01] times per SD, respectively) and with lower TLHQ relative to CEHC (0.93 [0.90, 0.98] and 0.93 [0.87, 0.98] times per SD, respectively). We observed similar associations for VAT (TLHQ: 0.94 [0.89, 0.99] times per SD), but not for aSAT. CONCLUSIONS Opposite to our research hypothesis, higher abdominal adiposity was moderately associated with lower levels of oxidized α-TOH metabolites, which might reflect lower vitamin E antioxidative activity in individuals with higher abdominal fat instead.
Best-practice clinical management of flares in people with osteoarthritis: A scoping review of behavioral, lifestyle and adjunctive treatments.
Seminars in arthritis and rheumatism. 2021;(4):749-760
INTRODUCTION Transient episodes of increased pain, stiffness or swelling are common in people with osteoarthritis (OA). Yet, evidence-based management strategies for lessening the impact of OA flares are rarely covered in clinical guidelines and have been identified as a gap by clinicians delivering OA care. We aimed to identify evidence on behavioral, lifestyle or other adjunctive flare management strategies that could be used by clinicians or consumers. MATERIALS AND METHODS A literature search between 1990-2020 was performed in three databases using a scoping methodology. We included qualitative or quantitative studies, and reviews that examined OA flare management, or that reported OA flare outcomes at timepoints ≤2 weeks post-intervention. Outcomes included any physical or psychological OA outcome treatable with a therapeutic intervention. RESULTS We included 9 studies, all of which examined the relationship between therapeutic exercise/ physical activity and OA flares. All studies reported pain outcomes at the knee. Two also included the hip. Only two studies examined specific management strategies for OA flares. Both favorably reported the benefits of undertaking an exercise program modified accordingly during an episode, but the quality of the evidence was low. DISCUSSION This scoping review highlights the paucity of evidence available on non-pharmacological treatments of OA flare management that could influence clinical practice. At present, there is no robust evidence to support or reject any specific therapies for OA flare management in clinical practice. Future work is needed, particularly around outcomes beyond pain, trajectories of symptom improvement, and for joints other than the knee.
Study protocol of the Health4Life initiative: a cluster randomised controlled trial of an eHealth school-based program targeting multiple lifestyle risk behaviours among young Australians.
BMJ open. 2020;(7):e035662
INTRODUCTION Lifestyle risk behaviours, including alcohol use, smoking, poor diet, physical inactivity, poor sleep (duration and/or quality) and sedentary recreational screen time ('the Big 6'), are strong determinants of chronic disease. These behaviours often emerge during adolescence and co-occur. School-based interventions have the potential to address risk factors prior to the onset of disease, yet few eHealth school-based interventions target multiple behaviours concurrently. This paper describes the protocol of the Health4Life Initiative, an eHealth school-based intervention that concurrently addresses the Big 6 risk behaviours among secondary school students. METHODS AND ANALYSIS A multisite cluster randomised controlled trial will be conducted among year 7 students (11-13 years old) from 72 Australian schools. Stratified block randomisation will be used to assign schools to either the Health4Life intervention or an active control (health education as usual). Health4Life consists of (1) six web-based cartoon modules and accompanying activities delivered during health education (once per week for 6 weeks), and a smartphone application (universal prevention), and (2) additional app content, for students engaging in two or more risk behaviours when they are in years 8 and 9 (selective prevention). Students will complete online self-report questionnaires at baseline, post intervention, and 12, 24 and 36 months after baseline. Primary outcomes are consumption of sugar-sweetened beverages, moderate-to-vigorous physical activity, sleep duration, sedentary recreational screen time and uptake of alcohol and tobacco use. ETHICS AND DISSEMINATION This study has been approved by the University of Sydney (2018/882), NSW Department of Education (SERAP no. 2019006), University of Queensland (2019000037), Curtin University (HRE2019-0083) and relevant Catholic school committees. Results will be presented to schools and findings disseminated via peer-reviewed journals and scientific conferences. This will be the first evaluation of an eHealth intervention, spanning both universal and selective prevention, to simultaneously target six key lifestyle risk factors among adolescents. TRIAL REGISTRATION NUMBER Australian New Zealand Clinical Trials Registry (ACTRN12619000431123), 18 March 2019.
'The long tail of Covid-19' - The detection of a prolonged inflammatory response after a SARS-CoV-2 infection in asymptomatic and mildly affected patients.
Plain language summary
‘Long COVID’ or the persistence of symptoms after SARS-CoV-2 infection, such as fatigue, is becoming increasingly common. As the emergence of the virus is still relatively recent in research terms, little is known about the long-term impact of the viruses infection. This study sought to generate further insights into the management and diagnostic of long COVID, by assessing a range of inflammatory markers from blood serum samples. Examined were 10 samples of health care workers with previous asymptomatic or moderate SARS-CoV-2 infections, compared to 10 samples of SARS-CoV-2 naive health care workers. The serum was analyzed by mass spectrometry using a customized panel of the 96 immune response associated proteins. Despite being mild to moderate cases, the results showed that even 40-60 days after infection, significant disturbance in the immune systems inflammatory response could be observed. Particularly markers that reflect anti-inflammatory pathways and mitochondrial stress. The study highlighted six of the most noteworthy proteins and included a brief description of their role. The authors suggest that analysing proteins by using targeted proteomic technology, could serve as a cost-effective strategy to further investigate the changes in inflammatory responses post SARS-CoV-2 infection. Which could help to aid the identification of potential treatment targets in the future. Relevant findings from this small study for clinical practice are that even mild to moderate SARS-CoV-2 infection can alter the inflammatory responses for months afterwards.
'Long Covid', or medical complications associated with post SARS-CoV-2 infection, is a significant post-viral complication that is being more and more commonly reported in patients. Therefore, there is an increasing need to understand the disease mechanisms, identify drug targets and inflammatory processes associated with a SARS-CoV-2 infection. To address this need, we created a targeted mass spectrometry based multiplexed panel of 96 immune response associated proteins. We applied the multiplex assay to a cohort of serum samples from asymptomatic and moderately affected patients. All patients had tested positive for a SARS-CoV-2 infection by PCR and were determined to be subsequently positive for antibodies. Even 40-60 days post-viral infection, we observed a significant remaining inflammatory response in all patients. Proteins that were still affected were associated with the anti-inflammatory response and mitochondrial stress. This indicates that biochemical and inflammatory pathways within the body can remain perturbed long after SARS-CoV-2 infections have subsided even in asymptomatic and moderately affected patients.
A randomised controlled trial of the effect of providing online risk information and lifestyle advice for the most common preventable cancers.
Preventive medicine. 2020;:106154
Few trial data are available concerning the impact of personalised cancer risk information on behaviour. This study assessed the short-term effects of providing personalised cancer risk information on cancer risk beliefs and self-reported behaviour. We randomised 1018 participants, recruited through the online platform Prolific, to either a control group receiving cancer-specific lifestyle advice or one of three intervention groups receiving their computed 10-year risk of developing one of the five most common preventable cancers either as a bar chart, a pictograph or a qualitative scale alongside the same lifestyle advice. The primary outcome was change from baseline in computed risk relative to an individual with a recommended lifestyle (RRI)1 at three months. Secondary outcomes included: health-related behaviours, risk perception, anxiety, worry, intention to change behaviour, and a newly defined concept, risk conviction. After three months there were no between-group differences in change in RRI (p = 0.71). At immediate follow-up, accuracy of absolute risk perception (p < 0.001), absolute and comparative risk conviction (p < 0.001) and intention to increase fruit and vegetables (p = 0.026) and decrease processed meat (p = 0.033) were higher in all intervention groups relative to the control group. The increases in accuracy and conviction were only seen in individuals with high numeracy and low baseline conviction, respectively. These findings suggest that personalised cancer risk information alongside lifestyle advice can increase short-term risk accuracy and conviction without increasing worry or anxiety but has little impact on health-related behaviour. Trial registration: ISRCTN17450583. Registered 30 January 2018.
Reply to: Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter.
Nature metabolism. 2019;(7):662-665
Comparative effects of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on carotid artery intima-media thickness progression: a network meta-analysis.
Cardiovascular diabetology. 2019;(1):14
BACKGROUND Carotid artery intima-media thickness (cIMT) progression is a surrogate marker of atherosclerosis with a high predictive value for future CVD risk. This study evaluates the comparative efficacies of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on cIMT progression. METHODS We conducted a network meta-analysis (NMA) to evaluate the relative efficacies of several drug classes in modifying cIMT progression. After a literature search in several electronic databases, studies were selected by following predetermined eligibility criteria. An inverse variance-heterogeneity model was used for NMA. Sensitivity analyses were performed to check the reliability of the overall NMA, and transitivity analyses were performed to examine the effects of modifiers on the NMA outcomes. RESULTS Data were taken from 47 studies (15,721 patients; age: 60.2 years [95% confidence interval (CI) 58.8, 61.6]; BMI: 27.2 kg/m2 [95% CI 26.4, 28.0]; and gender: 58.3% males [95% CI 48.3, 68.3]). Treatment duration was 25.8 months [95% CI 22.9, 28.7]. Of the 13 drug classes in the network, treatment with phosphodiesterase III inhibitors was the most effective in retarding annual mean cIMT against network placebo (weighted mean difference (WMD) - 0.059 mm [95% CI - 0.099, - 0.020) followed by the calcium channel blockers (WMD - 0.055 mm [95% CI - 0.099, 0.001]) and platelet adenosine diphosphate inhibitors (WMD - 0.033 mm [95% CI - 0.058, 0.008]). These 3 drug classes also attained the same positions when the NMA was conducted by using first-year changes in mean cIMT. In transitivity analyses, longer treatment duration, higher body mass index (BMI), and a higher baseline cIMT were found to be independently associated with a lesser reduction in annual mean cIMT. However, in a multivariate analysis with these 3 modifiers, none of these factors was significantly associated with annual change in mean cIMT. In the placebo group, age was inversely associated with annual change in mean cIMT independently. CONCLUSION Phosphodiesterase III inhibitors and calcium channel blockers are found more effective than other drug classes in retarding cIMT progression. Age, BMI, and baseline cIMT may have some impact on these outcomes.
Low-level ozone has both respiratory and systemic effects in African American adolescents with asthma despite asthma controller therapy.
The Journal of allergy and clinical immunology. 2018;(6):1974-1977.e3