Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of ...artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.
The Oxford WebQ is an online 24-hour dietary questionnaire that is appropriate for repeated administration in large-scale prospective studies, including the UK Biobank study and the Million Women ...Study. We compared the performance of the Oxford WebQ and a traditional interviewer-administered multiple-pass 24-hour dietary recall against biomarkers for protein, potassium, and total sugar intake and total energy expenditure estimated by accelerometry. We recruited 160 participants in London, United Kingdom, between 2014 and 2016 and measured their biomarker levels at 3 nonconsecutive time points. The measurement error model simultaneously compared all 3 methods. Attenuation factors for protein, potassium, total sugar, and total energy intakes estimated as the mean of 2 applications of the Oxford WebQ were 0.37, 0.42, 0.45, and 0.31, respectively, with performance improving incrementally for the mean of more measures. Correlation between the mean value from 2 Oxford WebQs and estimated true intakes, reflecting attenuation when intake is categorized or ranked, was 0.47, 0.39, 0.40, and 0.38, respectively, also improving with repeated administration. These correlations were similar to those of the more administratively burdensome interviewer-based recall. Using objective biomarkers as the standard, the Oxford WebQ performs well across key nutrients in comparison with more administratively burdensome interviewer-based 24-hour recalls. Attenuation improves when the average value is taken over repeated administrations, reducing measurement error bias in assessment of diet-disease associations.
Nutrition and the circadian system Potter, Gregory D M; Cade, Janet E; Grant, Peter J ...
British journal of nutrition,
08/2016, Volume:
116, Issue:
3
Journal Article
Peer reviewed
Open access
The human circadian system anticipates and adapts to daily environmental changes to optimise behaviour according to time of day and temporally partitions incompatible physiological processes. At the ...helm of this system is a master clock in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN are primarily synchronised to the 24-h day by the light/dark cycle; however, feeding/fasting cycles are the primary time cues for clocks in peripheral tissues. Aligning feeding/fasting cycles with clock-regulated metabolic changes optimises metabolism, and studies of other animals suggest that feeding at inappropriate times disrupts circadian system organisation, and thereby contributes to adverse metabolic consequences and chronic disease development. 'High-fat diets' (HFD) produce particularly deleterious effects on circadian system organisation in rodents by blunting feeding/fasting cycles. Time-of-day-restricted feeding, where food availability is restricted to a period of several hours, offsets many adverse consequences of HFD in these animals; however, further evidence is required to assess whether the same is true in humans. Several nutritional compounds have robust effects on the circadian system. Caffeine, for example, can speed synchronisation to new time zones after jetlag. An appreciation of the circadian system has many implications for nutritional science and may ultimately help reduce the burden of chronic diseases.
Worldwide, the prevalence of dementia is increasing and diet as a modifiable factor could play a role. Meat consumption has been cross-sectionally associated with dementia risk, but specific amounts ...and types related to risk of incident dementia remain poorly understood.
We aimed to investigate associations between meat consumption and risk of incident dementia in the UK Biobank cohort.
Meat consumption was estimated using a short dietary questionnaire at recruitment and repeated 24-h dietary assessments. Incident all-cause dementia comprising Alzheimer disease (AD) and vascular dementia (VD) was identified by electronic linkages to hospital and mortality records. HRs for each meat type in relation to each dementia outcome were estimated in Cox proportional hazard models. Interactions between meat consumption and the apolipoprotein E (APOE) ε4 allele were additionally explored.
Among 493,888 participants included, 2896 incident cases of all-cause dementia, 1006 cases of AD, and 490 cases of VD were identified, with mean ± SD follow-up of 8 ± 1.1 y. Each additional 25 g/day intake of processed meat was associated with increased risks of incident all-cause dementia (HR: 1.44; 95% CI: 1.24, 1.67; P-trend < 0.001) and AD (HR: 1.52; 95% CI: 1.18, 1.96; P-trend = 0.001). In contrast, a 50-g/d increment in unprocessed red meat intake was associated with reduced risks of all-cause dementia (HR: 0.81; 95% CI: 0.69, 0.95; P-trend = 0.011) and AD (HR: 0.70; 95% CI: 0.53, 0.92; P-trend = 0.009). The linear trend was not significant for unprocessed poultry and total meat. Regarding incident VD, there were no statistically significant linear trends identified, although for processed meat, higher consumption categories were associated with increased risks. The APOE ε4 allele increased dementia risk by 3 to 6 times but did not modify the associations with diet significantly.
These findings highlight processed-meat consumption as a potential risk factor for incident dementia, independent of the APOE ε4 allele.
Assessment of diet in large epidemiological studies can be costly and time consuming. An automated dietary assessment system could potentially reduce researcher burden by automatically coding food ...records. myfood24 (Measure Your Food on One Day) an online 24-h dietary assessment tool (with the flexibility to be used for multiple 24 h-dietary recalls or as a food diary), has been developed for use in the UK population. Development of myfood24 was a multi-stage process. Focus groups conducted with three age groups, adolescents (11-18 years) (n = 28), adults (19-64 years) (n = 24) and older adults (≥ 65 years) (n = 5) informed the development of the tool, and usability testing was conducted with beta (adolescents n = 14, adults n = 8, older adults n = 1) and live (adolescents n = 70, adults n = 20, older adults n = 4) versions. Median system usability scale (SUS) scores (measured on a scale of 0-100) in adolescents and adults were marginal for the beta version (adolescents median SUS = 66, interquartile range (IQR) = 20; adults median SUS = 68, IQR = 40) and good for the live version (adolescents median SUS = 73, IQR = 22; adults median SUS = 80, IQR = 25). Myfood24 is the first online 24-h dietary recall tool for use with different age groups in the UK. Usability testing indicates that myfood24 is suitable for use in UK adolescents and adults.
Ever more evidence associates short sleep with increased risk of metabolic diseases such as obesity, which may be related to a predisposition to non-homeostatic eating. Few studies have concurrently ...determined associations between sleep duration and objective measures of metabolic health as well as sleep duration and diet, however. We therefore analyzed associations between sleep duration, diet and metabolic health markers in UK adults, assessing associations between sleep duration and 1) adiposity, 2) selected metabolic health markers and 3) diet, using National Diet and Nutrition Survey data. Adults (n = 1,615, age 19-65 years, 57.1% female) completed questions about sleep duration and 3 to 4 days of food diaries. Blood pressure and waist circumference were recorded. Fasting blood lipids, glucose, glycated haemoglobin (HbA1c), thyroid hormones, and high-sensitivity C-reactive protein (CRP) were measured in a subset of participants. We used regression analyses to explore associations between sleep duration and outcomes. After adjustment for age, ethnicity, sex, smoking, and socioeconomic status, sleep duration was negatively associated with body mass index (-0.46 kg/m2 per hour, 95% CI -0.69 to -0.24 kg/m2, p < 0.001) and waist circumference (-0.9 cm per hour, 95% CI -1.5 to -0.3cm, p = 0.004), and positively associated with high-density lipoprotein cholesterol (0.03 mmol/L per hour, 95% CI 0.00 to 0.05, p = 0.03). Sleep duration tended to be positively associated with free thyroxine levels and negatively associated with HbA1c and CRP (p = 0.09 to 0.10). Contrary to our hypothesis, sleep duration was not associated with any dietary measures (p ≥ 0.14). Together, our findings show that short-sleeping UK adults are more likely to have obesity, a disease with many comorbidities.
Deoxynivalenol (DON), the mycotoxin produced mainly by
and found in contaminated cereal-based foodstuff, has been consistently detected in body fluids in adults. Available data in children and ...adolescents are scarce. This study assessed urinary DON concentrations in children aged 3-9 years (
= 40) and adolescents aged 10-17 years (
= 39) in the UK. Morning urine samples were collected over two consecutive days and analysed for free DON (un-metabolised form), DON-glucuronides (DON-GlcA), deepoxy deoxynivalenol (DOM-1), and total DON (sum of free DON, DON-GlcA, and DOM-1). Total DON was detected in the urine of >95% of children and adolescents on both days. Mean total DON concentrations (ng/mg creatinine) were 41.6 and 21.0 for children and adolescents, respectively. The greatest total DON levels were obtained in female children on both days (214 and 219 ng/mg creatinine on days 1 and 2, respectively). Free DON and DON-GlcA were detected in most urine specimens, whereas DOM-1 was not present in any sample. Estimation of dietary DON exposure suggested that 33-63% of children and 5-46% of adolescents exceeded current guidance regarding the maximum provisional tolerable daily intake (PMTDI) for DON. Although moderate mean urinary DON concentrations were shown, the high detection frequency of urinary DON, the maximum biomarker concentrations, and estimated dietary DON exposure are concerning.
Online dietary assessment tools can reduce administrative costs and facilitate repeated dietary assessment during follow-up in large-scale studies. However, information on bias due to measurement ...error of such tools is limited. We developed an online 24-h recall (myfood24) and compared its performance with a traditional interviewer-administered multiple-pass 24-h recall, assessing both against biomarkers.
Metabolically stable adults were recruited and completed the new online dietary recall, an interviewer-based multiple pass recall and a suite of reference measures. Longer-term dietary intake was estimated from up to 3 × 24-h recalls taken 2 weeks apart. Estimated intakes of protein, potassium and sodium were compared with urinary biomarker concentrations. Estimated total sugar intake was compared with a predictive biomarker and estimated energy intake compared with energy expenditure measured by accelerometry and calorimetry. Nutrient intakes were also compared to those derived from an interviewer-administered multiple-pass 24-h recall.
Biomarker samples were received from 212 participants on at least one occasion. Both self-reported dietary assessment tools led to attenuation compared to biomarkers. The online tools resulted in attenuation factors of around 0.2-0.3 and partial correlation coefficients, reflecting ranking intakes, of approximately 0.3-0.4. This was broadly similar to the more administratively burdensome interviewer-based tool. Other nutrient estimates derived from myfood24 were around 10-20% lower than those from the interviewer-based tool, with wide limits of agreement. Intraclass correlation coefficients were approximately 0.4-0.5, indicating consistent moderate agreement.
Our findings show that, whilst results from both measures of self-reported diet are attenuated compared to biomarker measures, the myfood24 online 24-h recall is comparable to the more time-consuming and costly interviewer-based 24-h recall across a range of measures.
Nanomaterial-based drug delivery vehicles are able to deliver therapeutics in a controlled, targeted manner. Currently, however, there are limited analytical methods that can detect both nanomaterial ...distributions and their biochemical effects concurrently. In this study, we demonstrate that matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI) can be used together to obtain nanomaterial distributions and biochemical consequences. These studies employ nanoparticle-stabilized capsules (NPSCs) loaded with siRNA as a testbed. MALDI-MSI experiments on spleen tissues from intravenously injected mice indicate that NPSCs loaded with anti-TNF-α siRNA cause changes to the lipid composition in white pulp regions of the spleen, as anticipated, based on pathways known to be affected by TNF-α, whereas NPSCs loaded with scrambled siRNA do not cause the predicted changes. Interestingly, LA-ICP-MSI experiments reveal that the NPSCs primarily localize in the red pulp, suggesting that the observed changes in lipid composition are due to diffusive rather than localized effects on TNF-α production. Such information is only accessible by combining data from the two modalities, which we accomplish by using the heme signals from MALDI-MSI and iron signals from LA-ICP-MSI to overlay the images. Several unexpected changes in lipid composition also occur in regions where the NPSCs are found, suggesting that the NPSCs themselves can influence tissue biochemistry as well.
A wide variety of agents activate AMPK, but in many cases the mechanisms remain unclear. We generated isogenic cell lines stably expressing AMPK complexes containing AMP-sensitive (wild-type, WT) or ...AMP-insensitive (R531G) γ2 variants. Mitochondrial poisons such as oligomycin and dinitrophenol only activated AMPK in WT cells, as did AICAR, 2-deoxyglucose, hydrogen peroxide, metformin, phenformin, galegine, troglitazone, phenobarbital, resveratrol, and berberine. Excluding AICAR, all of these also inhibited cellular energy metabolism, shown by increases in ADP:ATP ratio and/or by decreases in cellular oxygen uptake measured using an extracellular flux analyzer. By contrast, A769662, the Ca2+ ionophore, A23187, osmotic stress, and quercetin activated both variants to varying extents. A23187 and osmotic stress also increased cytoplasmic Ca2+, and their effects were inhibited by STO609, a CaMKK inhibitor. Our approaches distinguish at least six different mechanisms for AMPK activation and confirm that the widely used antidiabetic drug metformin activates AMPK by inhibiting mitochondrial respiration.
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► AMPK is activated by a wide variety of different stresses, drugs, and xenobiotics ► We have developed a sensitive method to test which activators are AMP mediated ► Most, e.g., metformin and resveratrol, inhibit mitochondrial function and elevate AMP ► However, we can now distinguish six different mechanisms for AMPK activation
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