Diet plays an important role in chronic disease etiology, but some diet-disease associations remain inconclusive because of methodologic limitations in dietary assessment. Metabolomics is a novel ...method for identifying objective dietary biomarkers, although it is unclear what dietary information is captured from metabolites found in serum compared with urine.
We compared metabolite profiles of habitual diet measured from serum with those measured from urine.
We first estimated correlations between consumption of 56 foods, beverages, and supplements assessed by a food-frequency questionnaire, with 676 serum and 848 urine metabolites identified by untargeted liquid chromatography mass spectrometry, ultra-high performance liquid chromatography tandem mass spectrometry, and gas chromatography mass spectrometry in a colon adenoma case-control study (n = 125 cases and 128 controls) while adjusting for age, sex, smoking, fasting, case-control status, body mass index, physical activity, education, and caloric intake. We controlled for multiple comparisons with the use of a false discovery rate of <0.1. Next, we created serum and urine multiple-metabolite models to predict food intake with the use of 10-fold crossvalidation least absolute shrinkage and selection operator regression for 80% of the data; predicted values were created in the remaining 20%. Finally, we compared predicted values with estimates obtained from self-reported intake for metabolites measured in serum and urine.
We identified metabolites associated with 46 of 56 dietary items; 417 urine and 105 serum metabolites were correlated with ≥1 food, beverage, or supplement. More metabolites in urine (n = 154) than in serum (n = 39) were associated uniquely with one food. We found previously unreported metabolite associations with leafy green vegetables, sugar-sweetened beverages, citrus, added sugar, red meat, shellfish, desserts, and wine. Prediction of dietary intake from multiple-metabolite profiles was similar between biofluids.
Candidate metabolite biomarkers of habitual diet are identifiable in both serum and urine. Urine samples offer a valid alternative or complement to serum for metabolite biomarkers of diet in large-scale clinical or epidemiologic studies.
To assess the utility of measurement methods that may be more accurate and precise than traditional questionnaire-based estimates of habitual physical activity and sedentary behavior we compared the ...measurement properties of a past year questionnaire (AARP) and more comprehensive measures: an internet-based 24-h recall (ACT24), and a variety of estimates from an accelerometer (ActiGraph).
Participants were 932 adults (50-74 yr) in a 12-month study that included reference measures of energy expenditure from doubly labeled water (DLW) and active and sedentary time via activPAL.
Accuracy at the group level (mean differences) was generally better for both ACT24 and ActiGraph than the AARP questionnaire. The AARP accuracy for energy expenditure ranged from -4% to -13% lower than DLW, but its accuracy was poorer for physical activity duration (-48%) and sedentary time (-18%) versus activPAL. In contrast, ACT24 accuracy was within 3% to 10% of DLW expenditure measures and within 1% to 3% of active and sedentary time from activPAL. For ActiGraph, accuracy for energy expenditure was best for the Crouter 2-regression method (-2% to -7%), and for active and sedentary time the 100 counts per minute cutpoint was most accurate (-1% to 2%) at the group level. One administration of the AARP questionnaire was significantly correlated with long-term average from the reference measures (ρTX = 0.16-0.34) overall, but four ACT24 recalls had higher correlations (ρTX = 0.48-0.60), as did 4 d of ActiGraph assessment (ρTX = 0.54-0.87).
New exposure assessments suitable for use in large epidemiologic studies (ACT24, ActiGraph) were more accurate and had higher correlations than a traditional questionnaire. Use of better more comprehensive measures in future epidemiologic studies could yield new etiologic discoveries and possibly new opportunities for prevention.
Leisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood.
To determine the ...association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking.
We pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline, 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015.
Leisure-time physical activity of a moderate to vigorous intensity.
Incident cancer during follow-up.
A total of 1.44 million participants (median range age, 59 19-98 years; 57% female) and 186 932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR, 0.58; 95% CI, 0.37-0.89), liver (HR, 0.73; 95% CI, 0.55-0.98), lung (HR, 0.74; 95% CI, 0.71-0.77), kidney (HR, 0.77; 95% CI, 0.70-0.85), gastric cardia (HR, 0.78; 95% CI, 0.64-0.95), endometrial (HR, 0.79; 95% CI, 0.68-0.92), myeloid leukemia (HR, 0.80; 95% CI, 0.70-0.92), myeloma (HR, 0.83; 95% CI, 0.72-0.95), colon (HR, 0.84; 95% CI, 0.77-0.91), head and neck (HR, 0.85; 95% CI, 0.78-0.93), rectal (HR, 0.87; 95% CI, 0.80-0.95), bladder (HR, 0.87; 95% CI, 0.82-0.92), and breast (HR, 0.90; 95% CI, 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR, 1.27; 95% CI, 1.16-1.40) and prostate cancer (HR, 1.05; 95% CI, 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers.
Leisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings.
Prolonged sitting has emerged as a risk factor for early mortality, but the extent of benefit realized by replacing sitting time with exercise or activities of everyday living (i.e., nonexercise ...activities) is not known.
We prospectively followed 154,614 older adults (59-82 yr) in the National Institutes of Health-AARP Diet and Health Study who reported no major chronic diseases at baseline and reported detailed information about sitting time, exercise, and nonexercise activities. Proportional hazard models were used to estimate adjusted hazard ratios and 95% confidence intervals (HR (95% confidence interval)) for mortality. An isotemporal modeling approach was used to estimate associations for replacing sitting time with specific types of physical activity, with separate models fit for less active and more active participants to account for nonlinear associations.
During 6.8 yr (SD, 1.0) of follow-up, 12,201 deaths occurred. Greater sitting time (≥12 vs < 5 h·d(-1)) was associated with increased risk for all-cause and cardiovascular mortality. In less active adults (<2 h·d(-1) total activity), replacing 1 h·d(-1) of sitting with an equal amount of activity was associated with lower all-cause mortality for both exercise (HR, 0.58 (0.54-0.63)) and nonexercise activities (HR, 0.70 (0.66-0.74)), including household chores, lawn and garden work, and daily walking. Among more active participants (2+ h·d(-1) total activity), replacement of sitting time with purposeful exercise was associated with lower mortality (HR, 0.91 (0.88-0.94)) but not with nonexercise activity (HR, 1.00 (0.98-1.02)). Similar results were noted for cardiovascular mortality.
Physical activity intervention strategies for older adults often focus on aerobic exercise, but our findings suggest that reducing sitting time and engaging in a variety of activities is also important, particularly for inactive adults.
Abstract
The relationship between sleep and obesity or weight gain in adults, particularly older populations, remains unclear. In a cohort of 83,377 US men and women aged 51–72 years, we ...prospectively investigated the association between self-reported sleep duration and weight change over an average of 7.5 years of follow-up (1995–2004). Participants were free of cancer, heart disease, and stroke at baseline and throughout the follow-up. We observed an inverse association between sleep duration per night and weight gain in both men (P for trend = 0.02) and women (P for trend < 0.001). Compared with 7–8 hours of sleep, shorter sleep (<5 hours or 5–6 hours) was associated with more weight gain (in kilograms; men: for <5 hours, β = 0.66, 95% confidence interval (CI): 0.19, 1.13, and for 5–6 hours, β = 0.12, 95% CI: −0.02, 0.26; women: for <5 hours, β = 0.43, 95% CI: 0.00, 0.86, and for 5–6 hours, β = 0.23, 95% CI: 0.08, 0.37). Among men and women who were not obese at baseline, participants who reported less than 5 hours of sleep per night had an approximately 40% higher risk of developing obesity than did those who reported 7–8 hours of sleep (for men, odds ratio = 1.45, 95% CI: 1.06, 1.99; for women, odds ratio = 1.37, 95% CI: 1.04, 1.79). The association between short sleep and excess weight gain was generally consistent across different categories of age, educational level, smoking status, baseline body mass index, and physical activity level.
Summary Background Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant data meta-analyses of ...prospective studies of body-mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up. Methods Of 10 625 411 participants in Asia, Australia and New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 years, IQR 11·4–14·7), 3 951 455 people in 189 studies were never-smokers without chronic diseases at recruitment who survived 5 years, of whom 385 879 died. The primary analyses are of these deaths, and study, age, and sex adjusted hazard ratios (HRs), relative to BMI 22·5–<25·0 kg/m2. Findings All-cause mortality was minimal at 20·0–25·0 kg/m2 (HR 1·00, 95% CI 0·98–1·02 for BMI 20·0–<22·5 kg/m2 ; 1·00, 0·99–1·01 for BMI 22·5–<25·0 kg/m2 ), and increased significantly both just below this range (1·13, 1·09–1·17 for BMI 18·5–<20·0 kg/m2 ; 1·51, 1·43–1·59 for BMI 15·0–<18·5) and throughout the overweight range (1·07, 1·07–1·08 for BMI 25·0–<27·5 kg/m2 ; 1·20, 1·18–1·22 for BMI 27·5–<30·0 kg/m2 ). The HR for obesity grade 1 (BMI 30·0–<35·0 kg/m2 ) was 1·45, 95% CI 1·41–1·48; the HR for obesity grade 2 (35·0–<40·0 kg/m2 ) was 1·94, 1·87–2·01; and the HR for obesity grade 3 (40·0–<60·0 kg/m2 ) was 2·76, 2·60–2·92. For BMI over 25·0 kg/m2 , mortality increased approximately log-linearly with BMI; the HR per 5 kg/m2 units higher BMI was 1·39 (1·34–1·43) in Europe, 1·29 (1·26–1·32) in North America, 1·39 (1·34–1·44) in east Asia, and 1·31 (1·27–1·35) in Australia and New Zealand. This HR per 5 kg/m2 units higher BMI (for BMI over 25 kg/m2 ) was greater in younger than older people (1·52, 95% CI 1·47–1·56, for BMI measured at 35–49 years vs 1·21, 1·17–1·25, for BMI measured at 70–89 years; pheterogeneity <0·0001), greater in men than women (1·51, 1·46–1·56, vs 1·30, 1·26–1·33; pheterogeneity <0·0001), but similar in studies with self-reported and measured BMI. Interpretation The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This finding supports strategies to combat the entire spectrum of excess adiposity in many populations. Funding UK Medical Research Council, British Heart Foundation, National Institute for Health Research, US National Institutes of Health.
Late embryogenesis abundant (LEA) proteins are extremely hydrophilic proteins that were first identified in land plants. Intracellular accumulation is tightly correlated with acquisition of ...desiccation tolerance, and data support their capacity to stabilize other proteins and membranes during drying, especially in the presence of sugars like trehalose. Exciting reports now show that LEA proteins are not restricted to plants; multiple forms are expressed in desiccation-tolerant animals from at least four phyla. We evaluate here the expression, subcellular localization, biochemical properties, and potential functions of LEA proteins in animal species during water stress. LEA proteins are intrinsically unstructured in aqueous solution, but surprisingly, many assume their native conformation during drying. They are targeted to multiple cellular locations, including mitochondria, and evidence supports that LEA proteins stabilize vitrified sugar glasses thought to be important in the dried state. More in vivo experimentation will be necessary to fully unravel the multiple functional properties of these macromolecules during water stress.
Questionnaires that assess active and sedentary behaviors in large-scale epidemiologic studies are known to contain substantial errors. We present three options for improving measures of physical ...activity behaviors in large-scale epidemiologic studies, discuss the problems and prospects for each of these options, and highlight a new direction for measuring these behaviors in such studies.
Per‐ and polyfluoroalkyl substances (PFAS) are highly persistent endocrine‐disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We ...investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case‐control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultraperformance liquid chromatography‐tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype‐specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs lowest quartile of serum PFOS (ORs 95% CIs = 1.59 1.01‐2.50, 2.34 1.29‐4.23, and 2.19 1.21‐3.98, respectively) and elevated but nonstatistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER−, PR−, ER+/PR−, and ER−/PR− tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor‐positive tumors, and possibly between PFOA and receptor‐negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology.
What's new?
Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are synthetic chemicals with widespread use in industrial applications and consumer products. They also are endocrine disruptors with suspected links to cancer. Here, the authors investigated potential associations between prediagnostic serum PFOS and PFOA levels and risk of breast cancer subtypes among postmenopausal women. No association was found between PFOS or PFOA and breast cancer risk overall. However, PFOS levels were positively associated with hormone receptor‐positive breast tumors, and modest positive associations were observed between PFOA levels and receptor‐negative tumors. The findings warrant further investigation in studies incorporating breast tumor hormone receptor status.
Early epidemiologic studies of estrogen metabolism measured only 2-hydroxyestrone and 16α-hydroxyestrone and relied on direct enzyme immunoassays without purification steps. Eight breast cancer ...studies have used these assays with prospectively collected blood or urine samples. Results were inconsistent, and generally not statistically significant; but the assays had limited specificity, especially at the low concentrations characteristic of postmenopausal women. To facilitate continued testing in population-based studies of the multiple laboratory-based hypotheses about the roles of estrogen metabolites, a novel liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay was developed to measure concurrently all 15 estrogens and estrogen metabolites in human serum and urine, as unconjugated and total (glucuronidated+sulfated+unconjugated) concentrations. The assay has high sensitivity (lower limit of quantitation ∼1–2pmol/L), reproducibility (coefficients of variation generally ⩽5%), and accuracy. Three prospective studies utilizing this comprehensive assay have demonstrated that enhanced 2-hydroxylation of parent estrogens (estrone+estradiol) is associated with reduced risk of postmenopausal breast cancer. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort, the serum ratio of 2-hydroxylation pathway metabolites to parent estrogens was associated with a 28% reduction in breast cancer risk across extreme deciles (p-trend=.05), after adjusting for unconjugated estradiol and breast cancer risk factors. Incorporating this ratio into a risk prediction model already including unconjugated estradiol improved absolute risk estimates substantially (by ⩾14%) in 36% of the women, an encouraging result that needs replication. Additional epidemiologic studies of the role of estrogen metabolism in the etiology of hormone-related diseases and continued improvement of estrogen metabolism assays are justified.
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