Dietary Total Antioxidant Capacity, a Diet Quality Index Predicting Mortality Risk in US Adults: Evidence from the NIH-AARP Diet and Health Study.

Dietary total antioxidant capacity (TAC) is an index representing the total antioxidant power of antioxidants consumed via the diet. This study aimed to investigate the association between dietary TAC and mortality risk in the US adults using data from the NIH-AARP Diet and Health Study. A total of 468,733 adults aged 50-71 years were included. Dietary intake was assessed using a food frequency questionnaire. Dietary TAC from diet was calculated from antioxidants including vitamin C, vitamin E, carotenoids, and flavonoids, and TAC from dietary supplements was calculated from supplemental vitamin C, vitamin E, and beta-carotene. During a median follow-up of 23.1 years, 241,472 deaths were recorded. Dietary TAC was inversely associated with all-cause (hazard ratio (HR) for quintile 5 vs. quintile 1: 0.97, 95% confidence interval (CI): 0.96-0.99, p for trend < 0.0001) and cancer mortality (HR for quintile 5 vs. quintile 1: 0.93, 95% CI: 0.90-0.95, p for trend < 0.0001). However, dietary supplement TAC was inversely associated with cancer mortality risk only. These findings indicate that consuming a habitual diet high in antioxidants may reduce the risk of all-cause and cancer mortality and TAC from foods might confer greater health benefits than TAC from dietary supplements.

Childhood beverage intake and risk of hypertension and hyperlipidaemia in young adults.

An epidemiological analysis assessing beverage consumption and risk factors for cardiovascular disease was conducted. Participants were 9-16 years old at enrolment, completed food frequency questionnaires in 1996-2001 and self-reported outcomes in 2010-2014. Exclusion criteria included missing data on relevant variables and covariates, prevalent disease before 2005, and implausible/extreme weight or energy intake. Intakes of orange juice, apple/other fruit juice, sugar-sweetened beverages and diet soda were related to the risk of incident hypertension or hyperlipidaemia using Cox proportional hazards regression, adjusting for diet, energy intake, age, smoking, physical activity and body mass index. There were 9,043 participants with 618 cases of hypertension and 850 of hyperlipidaemia in 17 years of mean follow-up. Sugar-sweetened beverage intake but not fruit juice nor diet soda was associated with hypertension (hazard ratio (95% confidence interval): 1.16 (1.03, 1.31)) in males. This study can guide beverage consumption as it relates to early predictors of cardiovascular disease.

Nutrient Adequacy Is Associated with Reduced Mortality in US Adults.

BACKGROUND: Americans are underconsuming essential nutrients while overconsuming several nutrients, including sodium, saturated fat, and added sugars. Suboptimal nutrition may be linked with mortality risk; however, few studies have evaluated the associations of underconsumed and overconsumed nutrients in a comprehensive manner among the US population. OBJECTIVES: This study investigated the association between nutrient intake through diet and mortality focusing on adequacy, moderation, and macronutrient quality in US adults. METHODS: Based on the 1999-2010 NHANES, 20,602 adults aged ≥30 y were followed up until December 2015. Nutrient intake was assessed using a 1-d 24-h dietary recall. Adequacy of major underconsumed nutrients in the United States was evaluated using the RDA (percent of RDA) or Adequate Intake (percent of AI). Overconsumed nutrients for which moderation is needed were assessed based on various dietary recommendations. Macronutrient quality was evaluated using the ratio of carbohydrates to dietary fiber, essential amino acids, and EPA + DHA. The association between nutrient intake and mortality was evaluated using Cox proportional hazards regression analysis. RESULTS: Higher intakes of vitamin E, magnesium, iron, dietary fiber, and potassium relative to the RDA/AI were associated with lower all-cause mortality. High intake of vitamin A (tertile 3: ≥80.1% of RDA) was associated with lower mortality from cardiovascular disease (CVD; HR: 0.75; 95% CI: 0.57, 0.99) and cancer (HR: 0.76; 95% CI: 0.62, 0.94), and high intake of calcium (tertile 3: ≥87.8% of RDA) was inversely associated with cancer mortality (HR: 0.72; 95% CI: 0.56, 0.93). Higher intakes of essential amino acids and EPA + DHA evaluated as quartiles were inversely associated with all-cause and CVD mortality. CONCLUSIONS: These findings suggest that higher intakes of underconsumed nutrients and improving macronutrient quality are associated with lower risk of CVD and cancer deaths in US adults.

Relative Validity of Dietary Total Antioxidant Capacity for Predicting All-Cause Mortality in Comparison to Diet Quality Indexes in US Adults.

While traditionally diet quality index scores (DQIS) as noted later in this abstract have been used to predict health outcomes, dietary total antioxidant capacity (TAC), a useful tool for assessing total antioxidant power in the diet, may also be a novel predictor. This study evaluated the associations between dietary TAC and DQIS and all-cause mortality. Based on the National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2006, 23,797 US adults were followed-up until 2015. Dietary TAC and DQIS including the Healthy Eating Index-2015 (HEI-2015), Alternative Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) were calculated using a 1-day 24 h dietary recall. US adults in the highest quintiles of DQIS had lower rates of all-cause mortality compared to those in the lowest quintiles (HEI-2015 hazard ratio (HR): 0.87, 95% confidence interval (CI): 0.77-0.98; AHEI-2010 HR: 0.84, 95% CI: 0.74-0.94; aMED HR: 0.79, 95% CI: 0.69-0.90; DASH HR: 0.80, 95% CI: 0.70-0.92). Similarly, those in the highest quintile of dietary TAC also had a lower all-cause mortality than those in the lowest quintile (HR: 0.88, 95% CI: 0.79-0.98). These findings suggest that dietary TAC might be a relatively valid predictor of all-cause mortality in the US population compared to the DQIS.

Association between Urinary Cadmium to Zinc Intake Ratio with Adult Mortality in a Follow-Up Study of NHANES 1988-1994 and 1999-2004.

Cadmium (Cd) is a toxic heavy metal associated with increased mortality, but the effect of zinc (Zn) intake on the association between Cd and mortality is unknown. The objective of this study was to examine the association of urinary Cd to Zn intake ratio (Cd/Zn ratio) and mortality risk. In total, 15642 US adults in NHANES 1988-1994 and 1999-2004 were followed until 2011 (15-year mean follow-up). Of the 5367 total deaths, 1194 were attributed to cancer and 1677 were attributed to CVD. After adjustment for potential confounders, positive associations were observed between urinary Cd and all-cause mortality (HR for highest vs. lowest quartile: 1.38; 95% CI: 1.14-1.68) and cancer mortality (HR: 1.54; CI: 1.05-2.27). Urinary Cd was positively associated with cancer mortality among the lowest Zn consumers, and the association diminished among the highest Zn consumers. Positive relationships were observed between the Cd/Zn ratio and all-cause mortality (HR: 1.54; CI: 1.23-1.93), cancer mortality (HR: 1.65; CI: 1.11-2.47) and CVD mortality (HR: 1.49; CI: 1.18-1.88). In conclusion, these findings indicate that Zn intake may modify the association between Cd and mortality. Furthermore, the Cd/Zn ratio, which was positively associated with mortality from all causes, cancer, and CVD, may be an important predictor of mortality.

Inadequate fat or carbohydrate intake was associated with an increased incidence of type 2 diabetes mellitus in Korean adults: A 12-year community-based prospective cohort study.

AIMS: Few studies have focused on the relationship between long-term fat intake and type 2 diabetes mellitus (T2D) risk in Asia where fat intake is relatively lower than the Western countries. We examined association of dietary fat and carbohydrate intake with incidence of T2D among Korean adults. METHODS: Based on the data from the Korean Genome and Epidemiology Study, a total of 5595 adults aged 40-69 years without diabetes, cardiovascular diseases or any cancer at baseline were included. Dietary intake was measured by the validated semi-quantitative food frequency questionnaire. Cox proportional hazards regression analysis was used to calculate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 138-months, 1010 cases of T2D were newly determined. The proportion of participants with fat intake less than 15% of total energy and with carbohydrate intake more than 65% of total energy was 59.0% and 88.9%, respectively. After adjusting for confounders, a very-low-fat intake was associated with an increased risk of T2D (RR of Quartile 1 vs Quartile 4, 1.74; 95% CI, 1.18-2.57; p for trend = 0.0058) in women. A very-high-carbohydrate intake was associated with an increased risk of T2D in men (RR of Quartile 4 vs Quartile 1, 1.54; 95% CI, 1.03-2.30; p for trend = 0.0124) and women (RR of Quartile 4 vs Quartile 1, 1.69; 95% CI, 1.08-2.67; p for trend = 0.0376). CONCLUSIONS: A very-low-fat or very-high-carbohydrate intake may increase the T2D risk and might be associated with lower intake of various nutrients and unbalanced macronutrient composition.

Erratum: The Role of Red Meat and Flavonoid Consumption on Cancer Prevention: The Korean Cancer Screening Examination Cohort; Nutrients 2017, 9, 938.

The authors have requested the following corrections to their paper [...].

Associations of Dietary Antioxidants and Risk of Type 2 Diabetes: Data from the 2007-2012 Korea National Health and Nutrition Examination Survey.

Antioxidants are suggested to decrease risk of type 2 diabetes (T2D) by preventing progressive impairment of pancreatic ß-cell and endothelial function. This study was aimed to investigate the association between dietary antioxidants and risk of T2D in Korean adults based on a national representative data. A total of 24,377 adults (19-74 years) who completed one-day 24 h dietary recall and health examination were included. Dietary antioxidant intakes including α-carotene (p < 0.0001), lycopene (p = 0.0107), flavan-3-ols (p < 0.0001), and proanthocyanidins (p = 0.0075) were significantly higher in non-diabetic subjects than in diabetic subjects. After adjusting for confounding variables, the highest quartile group of α-carotene intake was associated with a 48% reduced risk of T2D in men (OR: 0.52, 95% CI: 0.34-0.80, p for trend = 0.0037) and a 39% reduced risk in women (OR: 0.61, 95% CI: 0.38-0.996, p for trend = 0.0377) compared to the lowest quartile group. Men in the highest quartile of ß-carotene intake showed lower risk of T2D (OR: 0.64, 95% CI: 0.42-0.97), but no significant decreasing trend. However, the intakes of total carotenoids and other antioxidants showed no significant association with the risk of T2D. These findings suggest that a further comprehensive approach which considers overall dietary pattern is required.

The Role of Red Meat and Flavonoid Consumption on Cancer Prevention: The Korean Cancer Screening Examination Cohort.

Markedly increased red meat consumption is a cancer risk factor, while dietary flavonoids may help prevent the disease. The purpose of this study was to investigate the associations of red meat and flavonoid consumption with cancer risk, based on data from 8024 subjects, drawn from the 2004-2008 Cancer Screening Examination Cohort of the Korean National Cancer Center. Hazard ratios (HRs) were obtained by using a Cox proportional hazard model. During the mean follow-up period of 10.1 years, 443 cases were newly diagnosed with cancer. After adjusting for age, there was a significant correlation between cancer risk and the daily intake of ≥43 g of red meat per day (HR 1.31; 95% CI 1.01, 1.71; p = 0.045), and total flavonoid intake tended to decrease cancer risk (HR 0.70; 95% CI 0.49, 0.99; highest vs. lowest quartile; p-trend = 0.073) in men. Following multivariable adjustment, there were no statistically significant associations between flavonoid intake and overall cancer risk in individuals with high levels of red meat intake. Men with low daily red meat intake exhibited an inverse association between flavonoid consumption and cancer incidence (HR 0.41; 95% CI 0.21, 0.80; highest vs. lowest; p-trend = 0.017). Additional research is necessary to clarify the effects of flavonoid consumption on specific cancer incidence, relative to daily red meat intake.

Meat and milk intake in the rice-based Korean diet: impact on cancer and metabolic syndrome.

Over a few decades, Korean diet has changed from traditional diet, mainly composed of rice and vegetables, to Westernised diet rich, in meat and milk, along with the economic development and globalisation. Increasing prevalence of diet-related chronic diseases such as cancer and metabolic syndrome (MetS) is becoming a heavy burden to society and requires further attention. In this review, the association of meat and milk consumption with cancer and MetS among Koreans was discussed. Previous meta-analyses showed that meat intake was positively associated with increased risk of cancers, especially colon, as well as obesity and type 2 diabetes mellitus, and that the intake of milk and dairy products was negatively associated with colorectal cancer, obesity, and type 2 diabetes mellitus, based on studies conducted mostly in Western countries. In Korea and other Asian countries, the association of meat and milk intake with cancers were inconclusive and varied by types of cancers. Conversely, milk intake was negatively associated with MetS risk as reported in Western countries. The difference in results between Korea and Western countries might come from the differences in dietary patterns and study designs. Most Koreans still maintain traditional dietary pattern, although rapid change towards Westernised diet is underway among the younger age group. Randomised clinical trials or prospective cohort studies with consideration of combined effects of various dietary factors in Korea and other Asian countries are needed to elucidate the impact of meat and milk or related dietary patterns in their diet.

Transient exposure to hydrogen peroxide inhibits the ubiquitination of phosphorylated IκBα in TNFα-stimulated HEK293 cells.

During ischemia-reperfusion injury, brief pre-exposure to oxidative stress renders organs resistant to subsequent severe damage. NF-κB is a transcription factor that is involved in reperfusion-induced inflammatory and immune responses. The activity of NF-κB has been shown to be modulated by oxidative stress in various cell types through different pathways. We studied the effect of pre-exposure to oxidative stress on subsequent NF-κB activation in TNFα-stimulated HEK293 cells. The cells were transiently exposed to 0.5 mM H(2)O(2) for 20 min, prior to stimulation with TNFα, and the subsequent expression of NF-κB-dependent genes and the levels of NF-κB signaling molecules were measured. Pre-exposure to H(2)O(2) significantly delayed the TNFα-induced expression of an NF-κB reporter gene and inflammatory proteins (intercellular adhesion molecule-1 and IL-1ß). The degradation of inhibitor of NF-κB α (IκBα) and the nuclear translocation of NF-κB were also delayed by H(2)O(2) treatment, whereas IκBα phosphorylation and IκB kinase activity were not changed. When we examined the ubiquitin/proteosome pathway in H(2)O(2)-treated cells, we could not detect significant changes in proteosomal peptidase activities, but we were able to detect a delay of IκBα poly-ubiquitination. Our results suggest that transient exposure to oxidative stress temporally inhibits NF-κB-dependent gene expression by suppressing the poly-ubiquitination of phosphorylated IκBα in HEK293 cells.

N-tosyl-L-phenylalanine chloromethyl ketone inhibits NF-kappaB activation by blocking specific cysteine residues of IkappaB kinase beta and p65/RelA.

N-Tosyl-L-phenylalanine chloromethyl ketone (TPCK), a serine/cysteine protease inhibitor, has been reported to inhibit expression of inflammatory mediators by blocking nuclear factor-kappaB (NF-kappaB) activation. We examined the effect of TPCK on the NF-kappaB activation pathway in HeLa cells by measuring the activity of IkappaB kinase (IKK) and p65/RelA-DNA binding. TPCK inhibited tumor necrosis factor-alpha-induced IKK activation and directly blocked IKK activity in vitro. TPCK-induced inhibition of NF-kappaB and IKK activation was abrogated by addition of the thiol-reducing agent dithiothreitol, suggesting that the effect of TPCK occurred through modification of a thiol group in IKK. Consistent with this, an IKKbeta mutant in which Cys-179 was substituted with alanine was not more susceptible to TPCK. Our result also showed that TPCK inhibits the DNA binding of transiently expressed p65/RelA in HeLa cells. Inhibition of p65/RelA-DNA binding was recovered in the presence of dithiothreitol, and substitution of Cys-38 with Ser in p65/RelA rendered the protein resistant to inhibition by TPCK. Mass spectrometry analysis of IKKbeta and p65/RelA isolated from cells treated with TPCK by UPLC-ESI-Q-TOF tandem MS revealed the labeling of Cys-179 of IKKbeta and Cys-38 of p65/RelA with a tosylphenylalanylmethyl group. These results suggest that TPCK inhibits NF-kappaB activation by directly modifying thiol groups on two different targets: Cys-179 of IKKbeta and Cys-38 of p65/RelA.

Treatment with N-tosyl-l-phenylalanine chloromethyl ketone after the onset of collagen-induced arthritis reduces joint erosion and NF-kappaB activation.

N-tosyl-l-phenylalanine chloromethyl ketone (TPCK) is known to inhibit NF-kappaB activation and the expression of inflammation mediators in cultured cells. We measured the potential of TPCK to inhibit the pathogenesis of collagen-induced arthritis by blocking NF-kappaB activation. Arthritis was induced in DBA/1J mice by the injection of bovine type II collagen in adjuvant on days 0 and 14. Mice received either TPCK (3 or 10 mg/kg, i.p.) or vehicle three times a week for 3 weeks starting on day 21. TPCK moderately reduced clinical disease activity scores, whereas it markedly suppressed histological indications of joint destruction. In vitro production of tumor necrosis factor-alpha, interleukin-6, and monocyte chemotactic protein-1 from lipopolysaccharide-stimulated spleen cells was also reduced by in vivo treatment with TPCK. Proliferation of cells isolated from spleen or draining lymph nodes and production of interferon-gamma and interleukin-17 in response to stimulation with type II collagen was decreased by TPCK. Moreover, nuclear NF-kappaB activity induced by collagen immunization was significantly reduced in mice treated with TPCK. Finally, osteoclast differentiation of bone marrow cells induced by macrophage colony-stimulating factor and receptor activator of NF-kappaB ligand was completely inhibited by TPCK. These results indicate that TPCK attenuates collagen-induced arthritis and bone erosion by suppressing NF-kappaB activation and thus expression of inflammatory and osteoclastogenic genes.