Causal associations of histidine and 12 site-specific cancers: a bidirectional Mendelian randomization study.

An increasing number of studies indicate that cancer patients' histidine (HIS) circulating levels have changed. However, the causality between HIS and cancer is still not well established. Thus, to ascertain the causal link between HIS and cancers, we performed a bidirectional Mendelian randomization (MR) analysis. Summary-level data are derived from publicly available genome-wide association studies (GWAS). The causal effects were mainly estimated using the inverse-variance weighted method (IVW). The weighted-median (WM) method and MR-Egger regression were conducted as sensitivity analyses. In the forward-MR, we found malignant neoplasm of respiratory system and intrathoracic organs (OR: 1.020; 95% CI: 1.006-1.035; pIVW = 0.007) genetically associated with circulating HIS. And there was no significant genetic correlation between HIS and another 11 site-specific cancers using IVW method. In the reversed-MR, we did not observe the causal relationship between HIS and 12 site-specific cancers. Our findings help clarify that HIS, as a biomarker for malignant neoplasms of respiratory system and intrathoracic organs, is causal rather than a secondary biomarker of the cancerous progression. The mechanism between histidine and cancer progression deserves further investigation.

Association of rest-activity circadian rhythm with chronic respiratory diseases, a cross-section survey from NHANES 2011-2014.

OBJECTIVE: A growing number of studies have examined the 24-h rest-activity characteristics in relation to health outcomes. Up to now, few studies have paid attention to the role of rest-activity circadian rhythm in chronic respiratory diseases (CRDs); therefore, to fill this gap, our study innovatively explored the association of rest-activity circadian rhythm indices with CRDs. METHODS: A total of 7412 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in this study. The rest-activity circadian rhythm indices were calculated using accelerometer data and were divided into quartiles to perform logistic regression. RESULTS: Participants in the highest quartile of Relative amplitude (RA) had a lower prevalence of emphysema, chronic bronchitis and asthma, compared to those in the lowest quartile. Participants in the highest quartile of Intradaily variability (IV) was associated with a higher prevalence of emphysema relative to those in the lowest quartile. Compared to those in the lowest quartile, participants in the highest quartile of the average activity of the most active continuous 10-h period (M10) had a lower prevalence of emphysema. Additionally, compared to those in the lowest quartile of the average activity of the least active continuous 5-h period (L5) and L5 start time, participants in the highest quartile had a higher prevalence of asthma. CONCLUSIONS: This study demonstrated that in general US adult population, disrupted rest-activity circadian rhythm was associated with a higher prevalence of CRDs.

The Association of Dietary Fiber Intake in Three Meals with All-Cause and Disease-Specific Mortality among Adults: The U.S. National Health and Nutrition Examination Survey, 2003-2014.

The timing of food intake can significantly alter the body's metabolism of nutrient intake and affect the occurrence of chronic diseases. However, whether and how the intake time of dietary fiber could influence mortality risks is largely unknown. This study aims to reveal the association between total dietary fiber intake and fiber intake at different times with all-cause, cancer, and cardiovascular disease (CVD) mortality rates. A total of 31,164 adults who enrolled in the National Health and Nutrition Examination Survey from 2003 to 2014 are included in this study. Dietary fiber intake was measured using 2-day, 24 h dietary recall. The main exposures in this study were the intake of dietary fiber at breakfast, lunch, and dinner via regression analysis of the residual method. The main outcomes were the all-cause, cancer, and CVD mortality rates. Cox proportional hazards regression models were used to evaluate the survival relationship between dietary fiber intake at different times and mortality rates. Among the 31,164 adults, 2915 deaths, including 631 deaths due to cancer and 836 deaths due to CVD, were documented. Firstly, after adjusting for potential confounders, compared to the participants in the lowest quintile of total dietary fiber intake, the participants in the highest quintile of fiber intake had lower all-cause (HR = 0.686, 95% CI: 0.589−0.799, p for trend <0.001) and cancer (HR = 0.606, 95% CI: 0.446−0.824, p for trend = 0.015) mortality risks. Secondly, compared to the participants in the lowest quintile of dietary fiber intake at dinner, the participants in the highest quintile of fiber intake had lower all-cause (HR = 0.796, 95% CI: 0.668−0.949, p for trend = 0.009) and cancer (HR = 0.564, 95% CI: 0.388−0.822, p for trend = 0.005) mortality risks. Furthermore, equivalently replacing each standard deviation of dietary fiber consumed at breakfast with that at dinner was associated with lower cancer mortality risks (HR = 0.846, 95% CI: 0.747−0.958). In conclusion, this study demonstrates that, in the NHANES (2003−2014) cohort, to reduce all-cause and cancer mortality risks, the optimal dietary fiber intake time is in the evening.

The association of minerals intake in three meals with cancer and all-cause mortality: the U.S. National Health and Nutrition Examination Survey, 2003-2014.

BACKGROUND: Intake time of diet has recently been demonstrated to be associated with the internal clock and circadian pattern. However, whether and how the intake time of minerals would influence the natural course of cancer was largely unknown. METHODS: This study aimed to assess the association of mineral intake at different periods with cancer and all-cause mortality. A total of 27,455 participants aged 18-85 years old in the National Health and Nutrition Examination Survey were recruited. The main exposures were the mineral intakes in the morning, afternoon and evening, which were categorized into quintiles, respectively. The main outcomes were mortality of cancer and all causes. RESULTS: During the 178,182 person-years of follow-up, 2680 deaths, including 601 deaths due to cancer, were documented. After adjusting for potential confounders, compared to the participants who were in the lowest quintile(quintile-1) of mineral intakes at dinner, the participants in the highest quintile intake(quintile-5) of dietary potassium, calcium and magnesium had lower mortality risks of cancer (HRpotassium = 0.72, 95% CI:0.55-0.94, P for trend = 0.023; HRcalcium = 0.74, 95% CI:0.57-0.98, P for trend = 0.05; HRmagnesium = 0.75, 95% CI:0.56-0.99, P for trend = 0.037) and all-cause (HRpotassium = 0.83, 95% CI:0.73-0.94, P for trend = 0.012; HRcalcium = 0.87, 95% CI:0.76-0.99, P for trend = 0.025; HRmagnesium = 0.85, 95% CI:0.74-0.97, P for trend = 0.011; HRcopper = 0.80, 95%CI: 0.68-0.94, P for trend = 0.012). Further, equivalently replacing 10% of dietary potassium, calcium and magnesium consumed in the morning with those in the evening were associated with lower mortality risk of cancer (HRpotassium = 0.94, 95%CI:0.91-0.97; HRcalcium = 0.95, 95%CI:0.92-0.98; HRmagnesium = 0.95, 95%CI: 0.92-0.98). CONCLUSIONS: This study demonstrated that the optimal intake time of potassium, calcium and magnesium for reducing the risk of cancer and all-cause mortality was in the evening.

Lean non-alcoholic fatty liver disease patients had comparable total caloric, carbohydrate, protein, fat, iron, sleep duration and overtime work as obese non-alcoholic fatty liver disease patients.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease that involves a complex interaction between genetics, diet, and lifestyle. Although closely related with obese subjects, it is also common in lean humans. This study aimed to characterize the diet and lifestyle of lean and obese NAFLD patients in China. METHODS: To characterize the diet and lifestyle of lean and obese NAFLD patients, we conducted a matched case-control study that included 351 Chinese adults. General characteristics, dietary intake, and lifestyle were gathered by using a valid and reliable dietary questionnaire. We compared the dietary intake and lifestyle between lean and obese NAFLD patients. RESULTS: All NAFLD patients had more total caloric, calorigenic nutrients (carbohydrate, fat, and protein), grain, potato, fruit, and iron with higher levels of waist circumference and overtime work but shorter sleep duration than their corresponding controls. Particularly, lean NAFLD patients consumed comparable total caloric, calorigenic nutrients, iron, sleep duration, and overtime work as obese NAFLD patients, though they consumed lower levels of grain, potato, and fruit (lean NAFLD patients vs. obese NAFLD patients: mean ± SD, g/day grain: 291.8 ± 83.8, 365.2 ± 89.0; potato: 63.5 ± 33.1, 80.4 ± 37.6; fruit: 324.3 ± 148.4, 414.0 ± 220.4; P < 0.0001). CONCLUSION: Non-alcoholic fatty liver disease patients had higher total caloric, calorigenic nutrients, grain, potato, fruit, iron, and overtime work but shorter sleep duration. Lean NAFLD patients had comparable total caloric, calorigenic nutrients, iron, sleep duration, and overtime work as obese NAFLD patients. These features could be used to the nutritional education and therapeutic guidance for lean NAFLD patients in the future.

Dietary manganese and type 2 diabetes mellitus: two prospective cohort studies in China.

AIMS/HYPOTHESIS: The association between dietary Mn and type 2 diabetes is unclear. We aimed to elucidate whether dietary Mn is associated with type 2 diabetes, to investigate whether this association is independent of dietary total antioxidant capacity (TAC) and to explore the underlying mechanisms in their association. METHODS: Two prospective cohorts of 3350 and 7133 Chinese adults (20-74 years old) were enrolled including, respectively, 244 and 578 individuals newly diagnosed with type 2 diabetes, with mean values of 4.2 and 5.3 years of follow-up. Cox's proportional-hazards regression and linear regression were performed to investigate the association between dietary Mn and type 2 diabetes (diagnosed by OGTT) or HbAlc and to analyse the joint association between dietary Mn and TAC. Restricted cubic spline (RCS) regression was applied to the non-linear association between dietary Mn and incidence of type 2 diabetes. Mediation analysis was applied to explore potential mediators in their association in a subgroup of 500 participants. RESULTS: Dietary Mn intakes were 4.58 ± 1.04 and 4.61 ± 1.08 (mean ± SD) mg/day in the two cohorts. Dietary Mn was inversely associated with type 2 diabetes incidence and HbAlc concentration in both cohorts (ptrend < 0.01 and <0.01 for type 2 diabetes, and ptrend < 0.01 and =0.02 for HbAlc, respectively, in each cohort) independent of TAC, adjusted for age, sex, BMI, tobacco use, alcohol consumption, physical activity, diabetes inheritance, total energy, carbohydrate, total fatty acids, fibre, calcium, Mg, hypertension, hyperlipidaemia, and impaired glucose tolerance or FBG (all at baseline). Their inverse association was stronger in the presence of diets with high, compared with low, TAC. In RCS, intakes of >6.01 and 6.10-6.97 mg/day were associated with a significantly lower type 2 diabetes incidence in the two respective cohorts. Mediation analysis showed that high plasma Mn and low oxidative stress (increased Mn superoxide dismutase and decreased 8-hydroxydeoxyguanosine) contributed to the association between dietary Mn and both type 2 diabetes and HbAlc. CONCLUSIONS/INTERPRETATION: Dietary Mn was inversely associated with type 2 diabetes independently of TAC. In addition, this association was stronger in a high- rather than low-TAC diet. Plasma Mn and oxidative stress were mediators in the association between dietary Mn and type 2 diabetes. Future studies on absolute Mn intake should be conducted to study the potential non-linearity and optimal levels of dietary Mn and type 2 diabetes.

Low-Carbohydrate, High-Protein, High-Fat Diets Rich in Livestock, Poultry and Their Products Predict Impending Risk of Type 2 Diabetes in Chinese Individuals that Exceed Their Calculated Caloric Requirement.

The evidence on the association between long-term low-carbohydrate, high-fat and high-protein diets and type 2 diabetes (T2D) is controversial. Until now, data is limited for Chinese populations, especially in considering the influence of extra energy intake. In this paper, we aimed to investigate the association of low-carbohydrate, high-fat and high-protein diets with type 2 diabetes (T2D) risk in populations consuming extra calories and those with normal caloric intake, We also determined whether the association is mediated by insulin resistance (IR) or ß-cell dysfunction. A total of 3644 subjects in the Harbin People's Health Study (Cohort 1, 2008-2012) and 7111 subjects in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases (Cohort 2, 2010-2015) were analyzed, with a median follow-up of 4.2 and 5.3 years, respectively. Multivariate relative risks (RRs) and their 95% confidence intervals (95% CIs) were calculated to estimate the association between low-carbohydrate, high-fat and high-protein diet and T2D in logistic regression models. The multivariate RRs (95% CIs) were 1.00, 2.24 (1.07, 4.72) and 2.29 (1.07, 4.88) (Ptrend = 0.04), and 1.00, 1.45 (0.91, 2.31) and 1.64 (1.03, 2.61) (Ptrend = 0.04) across tertiles of low-carbohydrate, high-fat and high-protein diet scores in the population consuming extra calories in Cohort 1 and Cohort 2, respectively. The association was no longer significant after adjustment for livestock and its products, or poultry and its products. The mediation analysis discovered that this association in the population consuming extra calories was insulin resistance mediated, in both Cohort 1 and Cohort 2. However, the association was not significant among participants overall and participants with normal caloric intake. Our results indicated that long-term low-carbohydrate, high-fat and high-protein diets were associated with increased T2D risk among the population consuming extra calories, which may be caused by higher intake of animal-origin fat and protein as well as lower intake of vegetables, fruit and fiber. Additionally, the association was mediated by IR. In the population consuming extra calories, reducing the intake of livestock, poultry and their products and increasing the intake of vegetables, fruit and fiber might protect this population from developing T2D.

Abnormal circulating amino acid profiles in multiple metabolic disorders.

AIM: To evaluate circulating amino acids (AA) profiles in obesity, type 2 diabetes (T2D) and metabolic syndrome (MetS). METHODS: Serum AA were profiled among 200; healthy, obese, T2D and MetS subjects matched by sex, age and BMI using ultra-high performance liquid chromatography tandem quadruple mass spectrometry (UPLC-TQ-MS). A meta-analysis, including 47 case-control studies (including the current study) on serum AA in obesity, T2D and MetS searched through October 2016 was conducted to explore the AA differences in obesity, T2D and MetS. RESULTS: In comparison with healthy controls, 14 AA (10 increased and 4 decreased) were significantly altered (P<0.05) in all non-healthy subjects. Also, mean differences of valine (obese: 34.13 [27.70, 40.56]µmol/L, P<0.001, T2D: 19.49 [3.31, 35.68]µmol/L, P<0.05, MetS: 29.18 [16.04, 42.33]µmol/L, P<0.001), glutamic acid (obese: 18.62 [11.64, 25.61]µmol/L, P<0.001, T2D: 19.94 [0.28, 39.61]µmol/L, P<0.05, MetS: 12.45 [3.98, 20.91]µmol/L, P<0.001), proline (obese: 16.72 [6.20, 27.24]µmol/L, P<0.001, T2D: 20.72 [15.82, 25.61]µmol/L, P<0.001, MetS: 29.95 [25.18, 34.71]µmol/L, P<0.001) and isoleucine (obese: 11.39 [8.54, 14.24]µmol/L, P<0.001, T2D: 7.37 [1.52, 13.22]µmol/L, P<0.05, MetS: 10.40 [4.90, 15.89]µmol/L, P<0.001) were significantly higher compared to healthy controls. Similarly, mean differences of glycine (obese: -30.99 [-39.69, -22.29]µmol/L, P<0.001, T2D: -30.37 [-41.80, -18.94]µmol/L, P<0.001 and MetS: -35.24 [-39.28, -31.21]µmol/L, P<0.001) were significantly lower compared to healthy controls. CONCLUSION: In both the case-control study and meta-analysis, obesity was related to the most circulating AA changes, followed by MetS and T2D. Valine, isoleucine, glutamic acid and proline increased, while Glycine decreased in all metabolic disorders.

Relationships of Dietary Histidine and Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study.

Our previous studies have demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women and high-fat diet-induced obese rats. However, the effects of dietary histidine on general population are not known. The objective of this Internet-based cross-sectional study was to evaluate the associations between dietary histidine and prevalence of overweight/obesity and abdominal obesity in northern Chinese population. A total of 2376 participants were randomly recruited and asked to finish our Internet-based dietary questionnaire for the Chinese (IDQC). Afterwards, 88 overweight/obese participants were randomly selected to explore the possible mechanism. Compared with healthy controls, dietary histidine was significantly lower in overweight (p < 0.05) and obese (p < 0.01) participants of both sexes. Dietary histidine was inversely associated with body mass index (BMI), waist circumference (WC) and blood pressure in overall population and stronger associations were observed in women and overweight/obese participants. Higher dietary histidine was associated with lower prevalence of overweight/obesity and abdominal obesity, especially in women. Further studies indicated that higher dietary histidine was associated with lower fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), 2-h postprandial glucose (2 h-PG), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), C-reactive protein (CRP), malonaldehyde (MDA) and vaspin and higher glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and adiponectin of overweight/obese individuals of both sexes. In conclusion, higher dietary histidine is inversely associated with energy intake, status of insulin resistance, inflammation and oxidative stress in overweight/obese participants and lower prevalence of overweight/obesity in northern Chinese adults.