Safety and impact of the Mediterranean diet in patients with chronic kidney disease: a pilot randomized crossover trial.

Introduction: Emerging evidence highlights the potential advantages of the Mediterranean diet (MD) in preserving kidney function and slowing chronic kidney disease (CKD) progression. However, interventional studies on the MD are scarce in East Asian populations. Methods: This randomized crossover trial aimed to assess the safety and short-term impact of the Mediterranean Proper Optimal Balance (MEDi-POB) diet in Korean patients with stage 3-4 CKD. Kidney function was assessed using the estimated glomerular filtration rate, which was calculated using the CKD Epidemiology Collaboration equation. Fifty patients with CKD were randomly assigned to two groups, each starting with a different 4-week intervention, followed by a 4-week washout period, followed by a switch to the other 4-week intervention. During the MEDi-POB intervention, patients received home delivery of meals twice daily, 5 days a week, while the control intervention comprised a conventional diet. Forty-six patients successfully completed the entire 12-week trial. Paired t-tests were conducted to assess mean differences between the two groups. A linear mixed model was used to adjust for sequence and period. Results: Dietary fat, fiber, and niacin intake were significantly higher following the MEDi-POB diet than following the control diet (p = 0.001 for fat, p < 0.001 for fiber, and p = 0.007 for niacin). The MEDi-POB diet also yielded slightly increased total CO2 levels (p = 0.043), indicating effective management of metabolic acidosis. Conversely, sodium and copper intake were significantly lower with the MEDi-POB diet (p = 0.032 and p = 0.037, respectively). Caloric intake increased, but body mass index slightly decreased from baseline after consuming the MEDi-POB diet. Dietary potassium intake exhibited a non-significant increase (p = 0.053), and no significant changes in serum (p = 0.883) and urine potassium levels (p = 0.087) occurred. Kidney function remained well-preserved following the MEDi-POB diet. Conclusion: These results indicate that the MEDi-POB diet is safe even in patients with advanced CKD, as it does not adversely affect serum and urine potassium levels and helps maintain kidney function.

Dietary Habits of Newly Diagnosed Patients with Breast Cancer in Korea.

BACKGROUND: In patients with breast cancer, a healthy diet can help reduce breast cancer-specific recurrence, mortality, and comorbid chronic disease rates. There have been few studies on dietary habits immediately after breast cancer diagnosis, especially those involving the Asian population. Therefore, this study aimed to compare the nutritional habits of newly diagnosed patients with breast cancer and the general population without cancer in Korea using propensity score (PS) matching. METHODS: We conducted a case-controlled study of 157 patients with breast cancer and 2,363 cancer-free control participants from the Korea National Health and Nutrition Examination Survey. The PS values for the predicted probability of patients with breast cancer and the general population were estimated using logistic regression analysis, including age and body mass index. The dietary patterns were assessed using a 24-hour recall of 1 day and the Food Frequency Questionnaire. RESULTS: PS matching showed that patients with breast cancer consumed fewer calories and carbohydrates; however, they consumed more protein and fat compared to the general population. Compared to the general population, patients with breast cancer consumed more healthy foods such as fish, seaweed, vegetables, fruit, mixed-grain rice, and nuts; however, they also consumed more soup, stew, and red meat. CONCLUSION: Newly diagnosed patients with breast cancer have some healthy dietary habits compared to the general population. However, there is considerable room for improvement in their diet quality. Our results support the need to develop tailored dietary recommendations for patients with breast cancer during the diagnostic and posttreatment periods to improve their diet quality.

Dietary Zinc Intake and All-Cause and Cardiovascular Mortality in Korean Middle-Aged and Older Adults.

We aimed to investigate the association between dietary zinc intake and total deaths, cancer, and cardiovascular disease death. In this prospective, 10-year, community-based cohort analysis, data from 143,050 adult participants (aged 40 years and older) were analyzed. Dietary zinc intake at baseline was assessed using a food frequency questionnaire. Harrell's C-index was used to determine the optimal cut-off of dietary zinc intake with the log-rank test. Using the Cox proportional hazards regression models, the association between dietary zinc intake and all-cause, cancer, and cardiovascular disease mortality was estimated using hazard ratios and 95% confidence intervals. During the mean 10.1 years of follow-up, 5436 participants expired, of whom 2355 died due to cancer and 985 died due to cardiovascular causes. After adjustment for confounders, dietary zinc intake was inversely associated with all-cause mortality (≤5.60 mg/day vs. >7.98 mg/day; hazard ratio, 1.13; 95% confidence interval, 1.01−1.25) and cardiovascular disease mortality (≤5.12 mg/day vs. >7.28 mg/day; hazard ratio, 1.42; 95% confidence interval, 1.11−1.81) but not with cancer mortality (≤5.60 mg/day vs. >10.08 mg/day; hazard ratio, 1.09; 95% confidence interval, 0.90−1.33). Dietary zinc intake was associated with a lower risk of all-cause mortality and cardiovascular disease mortality but not with cancer mortality. Our findings could suggest that recommending optimal dietary zinc intake is helpful for human health.

Association of Dietary Fiber Intake with All-Cause Mortality and Cardiovascular Disease Mortality: A 10-Year Prospective Cohort Study.

Although previous studies have established that dietary fiber (DF) intake reduces the total cardiovascular disease (CVD) mortality in general populations, limited studies have been conducted in individuals with pre-existing chronic conditions, especially in Asian countries. We aimed to investigate the association of DF intake with all-cause and CVD mortality in the general population and in the subpopulation with hypertension, diabetes, and dyslipidemia. We examined the relationship between DF intake and all-cause and CVD mortality using the Korean genome and epidemiology study. Diet was assessed using a food-frequency questionnaire at baseline. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) after adjusting for confounders. During the mean 10.1 years of follow-up, higher DF intake was significantly associated with a lower risk of all-cause mortality after adjusting for confounders (HR and 95% CIs for Q5 vs. Q1: 0.84 (0.76−0.93); p < 0.001). DF intake was inversely associated with a lower risk of CVD mortality after adjusting for the same confounders (HR and 95% CIs for Q5 vs. Q1: 0.61 (0.47−0.78); p < 0.001). Total DF intake was inversely associated with all-cause and CVD mortality in middle-aged and older adults.

Effects of Single Nucleotide Polymorphisms and Mediterranean Diet in Overweight or Obese Postmenopausal Women With Breast Cancer Receiving Adjuvant Hormone Therapy: A Pilot Randomized Controlled Trial.

Background and Aims: Weight management is recommended in overweight or obese breast cancer patients, as they have an increased risk of cancer recurrence and poor prognosis. Furthermore, identifying the relationships between genetic factors and nutrition could help suggest possible individualized nutritional solutions in weight management. The objective of this pilot randomized controlled trial was to investigate the influence of two obesity-associated single nucleotide polymorphisms and the Mediterranean diet intervention on weight loss and modification of nutrient intake and metabolic parameters in overweight or obese, postmenopausal, breast cancer patients receiving adjuvant hormone therapy. Methods: Seventy-eight breast cancer patients were randomly assigned to the Mediterranean diet (MeDiet) group or control group, and seventy-one were finally analyzed. Body composition, nutrient intake, and metabolic parameters were assessed at baseline and after the 8-week intervention. Fat mass and obesity-associated (FTO) rs7185735 and melanocortin-4 receptor (MC4R) rs476828 variants were genotyped. Results: We found that both variants did not influence weight loss or improvement of metabolic parameters within the Mediterranean diet intervention. Intake of saturated fatty acid (SFA) and trans fat was significantly increased in C carriers compared with the TT genotype of MC4R rs476828 only in the control group (p = 0.002 for SFA; p = 0.016 for trans fat), whereas no significant difference was observed between genotypes in the MeDiet group. There were statistically significant interactions between MC4R rs476828 and dietary intervention for changes in SFA intake (p = 0.009) and trans fat intake (p = 0.049). Conclusion: Our data suggest that considering the effects of genotype may be more necessary when the Mediterranean diet is not followed and that this diet may have a protective role against the effects of certain genotypes. Further studies are required to determine the potential mechanism of the observed gene-diet interaction. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04045392].

The Association Between Total Protein Intake and All-Cause Mortality in Middle Aged and Older Korean Adults With Chronic Kidney Disease.

Background and Aims: Over the past decades, the optimum protein intake for patients with chronic kidney disease (CKD) has been an important, controversial issue. Dietary protein restriction has been commonly recommended for patients with CKD for preserving kidney function. However, evidence of the associations between long-term protein intake and mortality is not consistent in patients with CKD. Therefore, we aimed to examine the associations between total protein intake and all-cause mortality in Korean adults with CKD. Methods: From three sub-cohorts of the Korean Genome and Epidemiology Study (KoGES) starting from 2001, total 3,892 participants with eGFR < 60 mL/min/1.73 m2 (CKD stage 3-5) were included in this study. Dietary data were collected using food-frequency questionnaires at baseline. Deaths were followed from 2001 to 2019. Cox proportional hazards regression model was used to evaluate the association between protein intake and all-cause mortality. Results: During a median follow-up (min-max) of 11.1 years (0.3-15.1), 602 deaths due to all causes of mortality were documented. After adjustment for covariates, higher total protein intake was not associated with all-cause mortality [highest vs. lowest quintile of total protein intake (g/kg/day) and proportion (%) (Q5 vs. Q1), HR = 1.14 (0.75-1.72), and HR = 0.87 (0.67-1.13)] in CKD stage 3-5 patients. Conclusion: Dietary protein intake was not associated with mortality from all causes in patients with CKD. Further research is needed to establish optimal protein intake levels and examine the impact of the dietary source of protein on various health outcomes and mortality in CKD.

Effects of a Calorie-Restricted Mediterranean-Style Diet on Plasma Lipids in Hypercholesterolemic South Korean Patients.

The objective of this randomized cross-over trial was to evaluate the short term effects of a calorie-restricted Korean style Mediterranean diet (KMD) versus a calorie-restricted conventional diet on lipid profile and other metabolic parameters in hypercholesterolemic patients. Ninety-two patients with hypercholesterolemia were randomly assigned to two groups and switched to the other group following a 4-week intervention after a 2-week washout period. While participants during KMD intervention period received home delivery of two meals daily except for weekends, those during the control group were advised to consume a conventional diet. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) significantly decreased in KMD group even after adjusting for age, sex, total energy intake changes, alcohol consumption, smoking status, and physical activity changes (all p < 0.05). Anthropometric parameters, white blood cell (WBC), fasting glucose, fasting insulin, HOMA-IR, and fatty liver index (FLI) also significantly decreased after KMD intervention (all p < 0.05). In addition, WBC, fasting glucose, total cholesterol, LDL-C and FLI were significantly decreased even after adjusting for weight reduction changes. Calorie-restricted KMD not only helps to treat dyslipidemia by improving the lipid parameters but also has beneficial effects on reducing cardiovascular risk by improving chronic inflammation, insulin resistance, and fatty liver.

Association between nutrition education, dietary habits, and body image misperception in adolescents.

BACKGROUND AND OBJECTIVES: In adolescents, adequate nutrition education is essential for making decisions regarding healthy eating habits. We aimed to investigate differences in dietary habits and body image misperception according to nutrition education status. METHODS AND STUDY DESIGN: We analyzed 60,389 adolescents aged 12-18 years old, using the 2017 Korea Youth Risk Behavior Web-based Survey data. Participants were divided into nutrition-educated (EDU) and uneducated (non-EDU) groups, according to nutrition education status within the past year. Skipping breakfast was defined as skipping breakfast ≥5 times/week. Desirable dietary behaviors were divided into the frequency of consumption of 3 items: vegetables ≥1 time/day, milk ≥1 time/day, and fruits ≥1 time/day. Participants with normal weight who reported being slightly fat or very fat were defined as having body image misperception. RESULTS: Compared to the non-EDU group, the odds ratio (OR) and 95% confidence interval (CI) for desirable dietary behaviors in the EDU group were 1.08 (1.04-1.13), 1.14 (1.09-1.19), and 1.16 (1.12-1.20) for the intake of fruits, milk, and vegetables, respectively. The EDU group was less associated with skipping breakfast than the non-EDU group (OR=0.91, 95% CI: 0.87-0.95, p<0.001). The OR and 95% CI of body image misperception in the EDU group were lower than in the non-EDU group (OR=0.92, 95% CI: 0.87- 0.97, p<0.001). CONCLUSIONS: Nutrition education have positive effects on healthy dietary behaviors. It also shows a negative association with body image misperception, confirming the importance of nutrition education at school.

Association of milk consumption frequency on muscle mass and strength: an analysis of three representative Korean population studies.

PURPOSE: Sarcopenia is an involuntary loss of muscle mass, strength, and physical performance associated with aging. Sarcopenia contributes to adverse health outcomes. Milk contains essential amino acids important for maintaining muscle. We investigated the relationships among milk consumption frequency (MCF), muscle mass, and strength in Korean adults. METHODS: We analyzed the data from 16,173 adults in the 2008-2011 Korean National Health and Nutrition Examination Survey (KNHANES), 13,537 adults in the 2014-2016 KNHANES, and 8254 adults in the Korean Genome and Epidemiology Study (KoGES). MCF was divided into two groups: (1) MCF less than once per day (MCF < 1 group) and (2) MCF greater than or equal to once per day (MCF ≥ 1 group). Low skeletal muscle mass index (LSMI) was defined using the Foundation for the National Institutes of Health sarcopenia project criteria for low muscle mass. Muscle strength was measured using the hand-grip strength test. RESULTS: The odds ratio (95% confidence interval) for LSMI in the MCF < 1 group was 1.250 (1.013-1.543) after adjusting for confounding factors, compared with the MCF ≥ 1 group (2008-2011 KNHANES). The adjusted mean for hand-grip strength was higher in the MCF ≥ 1 group (2014-2016 KNHANES). After a mean follow-up of 9 years, fat-free mass/body mass index was higher in the MCF ≥ 1 group than the MCF < 1 group (KoGES). CONCLUSION: We found that MCF ≥ 1 was significantly associated with higher skeletal muscle index and muscle strength than lower MCF. Milk consumption could help prevent sarcopenia in adults.

Association between early nutritional risk and overall survival in patients with advanced pancreatic cancer: A single-center retrospective study.

BACKGROUND & AIMS: We investigated the predictors of overall survival (OS) among Korean patients with advanced pancreatic cancer (PC) according to their baseline nutritional status. METHODS: We retrospectively reviewed the data of 412 inpatients with PC between January 2007 and February 2015 at the Department of Oncology of the Gangnam Severance Hospital, Korea. Data on demographic and clinical parameters were collected from electronic medical records, and OS was estimated using the Kaplan-Meier method. Stepwise Cox regression analysis was used to determine the factors associated with survival. Patients with a Nutritional Risk Screening (NRS) 2002 score <3 were classified as "no-risk; " those with a score of 3 were classified as "moderate-risk; " and those with a score of ≥4 were classified as "high-risk." RESULTS: Following nutritional screening at baseline, 194 patients (47.1%, mean age 61.8 ± 9.9 years) were classified as the "no risk" group; 81 patients (19.7%, mean age 65.4 ± 10.8 years), as the "moderate risk" group; and 137 patients (33.3%, mean age 67.8 ± 12.0 years), as the "high risk" group. Predictors of survival were NRS 2002 score (hazard ratio [HR] = 1.238; 95% confidence interval [CI] = 1.143-1.341), percentage of lymphocytes (HR = 0.973; 95% CI = 0.962-0.984), C-reactive protein level (HR = 1.003; 95% CI = 1.001-1.006), carcinoembryonic antigen level (HR = 1.000; 95% CI = 1.000-1.000), and carbohydrate antigen 19-9 level (HR = 1.000; 95% CI = 1.000-1.000). Kaplan-Meier survival analysis showed significant differences in the median OS among the NRS 2002 groups: "no risk" group: 12.3 ± 0.4 months (95% CI: 11.47-13.13 months); "moderate risk" group: 6.5 ± 0.9 months (95% CI: 4.78-8.17 months); and "high risk" group: 5.5 ± 0.6 months (95% CI: 4.31-6.69 months). CONCLUSIONS: A good baseline nutritional status was associated with OS among Korean patients with advanced PC. An improvement in the nutritional status of patients with advanced PC through baseline nutritional interventions is therefore necessary to prolong OS.

Novel JAK1-selective benzimidazole inhibitors with enhanced membrane permeability.

The previously identified Janus kinase 1 (JAK1)-selective inhibitor, 1-(2-aminoethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole-5-carboxamide (2), suffered from low cell permeability, which resulted in poor pharmacokinetic properties. In this study, by introducing less polar hydrogen bond donors at N(1) (a hydroxyalkyl or a methylaminoalkyl group) and C2 (a cyclohexanol group) positions, a series of novel benzimidazole derivatives were prepared, which exhibited selective JAK1 inhibitory activity (IC50 against JAK1=0.08-0.15µM; JAK1-selectivity=26-40 fold vs JAK2, 12-23 fold vs JAK3, and 38-54 fold vs Tyk2) along with significantly increased lipophilicity (3.3-15.8 times) as well as membrane permeability (6.3-12 times).

Benzimidazole Derivatives as Potent JAK1-Selective Inhibitors.

The Janus kinase (JAK) family comprises four members (JAK1, JAK2, JAK3, and Tyk2) that play a key role in mediating cytokine receptor signaling. JAK inhibition thus modulates cytokine-mediated effects. In particular, selective inhibition of JAK1 or JAK3 may provide an efficient therapeutic agent for the treatment of inflammatory diseases, with minimized side effects. In this study, as part of our continued efforts to develop a selective JAK1 inhibitor, a series of 1,2-disubstituted benzimidazole-5-carboxamide derivatives was prepared and their inhibitory activities against all four JAK isozymes were evaluated. A clear structure-activity relationship was observed with respect to JAK1 selectivity; this highlighted the importance of hydrogen bond donors at both N(1) and R2 positions located within a specific distance from the benzimidazole core. One of the synthesized compounds, 1-(2-aminoethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole-5-carboxamide (5c), showed remarkable JAK1 selectivity (63-fold vs JAK2, 25-fold vs JAK3, and 74-fold vs Tyk2). Molecular docking revealed that the 2-aminoethyl and piperidin-4-yl substituents of 5c function as probes to differentiate the ATP-binding site of JAK1 from that of JAK2, resulting in preferential JAK1 binding. A kinase panel assay confirmed the JAK1 selectivity of 5c, which showed no appreciable inhibitory activity against 26 other protein kinases at 10 µM.

Paenibacillus swuensis sp. nov., a bacterium isolated from soil.

Strain DY6(T), a Gram-positive endospore-forming motile rod-shaped bacterium, was isolated from soil in South Korea and characterized to determine its taxonomic position. Phylogenetic analyses based on the 16S rRNA gene sequence of strain DY6(T) revealed that strain DY6(T) belongs to the genus Paenibacillus in the family Paenibacillaceae in the class Bacilli. The highest degree of sequence similarities of strain DY6(T) were found with Paenibacillus gansuensis B518(T) (97.9%), P. chitinolyticus IFO 15660(T) (95.3%), P. chinjuensis WN9T (94.7%), and P. rigui WPCB173(T) (94.7%). Chemotaxonomic data revealed that the predominant fatty acids were anteiso-C(15:0) (38.7%) and C(16:0) (18.0%). A complex polar lipid profile consisted of major amounts of diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylglycerol. The predominant respiratory quinone was MK-7. Based on these phylogenetic, chemotaxonomic, and phenotypic data, strain DY6(T) (=KCTC 33026(T) =JCM 18491(T)) should be classified as a type strain of a novel species, for which the name Paenibacillus swuensis sp. nov. is proposed.

Avoidable causes of delayed enteral nutrition in critically ill children.

To evaluate the incidence of delayed enteral nutrition (EN) and identify avoidable causes of delay, we retrospectively reviewed medical records of 200 children (median age [range]; 37.5 [1-216] months) who stayed in the intensive care unit (ICU) for a minimum of 3 days. Among 200 children, 115 received EN following ICU admission with a median time of EN initiation of 5 days after admission. Of these, only 22 patients achieved the estimated energy requirement. A significant decrease in the final z score of weight for age from the initial assessment was observed in the non-EN group only (-1.3±2.17 to -1.57±2.35, P<0.001). More survivors than non-survivors received EN during their ICU stay (61.2% vs 30.0%, P=0.001) and received EN within 72 hr of ICU admission (19.8% vs 3.3%, P=0.033). The most common reason for delayed EN was gastrointestinal (GI) bleeding, followed by altered GI motility and hemodynamic instability. Only eight cases of GI bleeding and one case of altered GI motility were diagnosed as active GI bleeding and ileus, respectively. This study showed that the strategies to reduce avoidable withholding EN are necessary to improve the nutrition status of critically ill children.

Effect of nutritional risk at admission on the length of hospital stay and mortality in gastrointestinal cancer patients.

This retrospective study was conducted to determine whether increased length of hospital stay (LOS) and mortality are associated with nutritional risk upon hospital admission in gastrointestinal cancer patients, using a computerized screening tool developed by a university hospital. We included adult gastrointestinal cancer patients whose hospital stays ranged from 24 hours to 90 days. The sample included 4,345 patients. The average age of the patients was 60.5 ± 11.4 years and 2,959 (68.1%) were males. The mean of LOS was 8.2 ± 8.2 days and the mortality rate was 3.4% (n = 146). The majority of the patients were at low risk (LG) (n = 3,102 [71.4%]), while 779 patients (17.9%) were at moderate risk (MG), and 464 (10.7%) were at high risk (HG). In comparing the three groups based on nutritional risk, hospital LOS was significantly longer in the HG (11.4 ± 11.4 days) than it was in the LG (7.7 ± 7.9 days) and the MG (7.9 ± 7.9 days) (p < 0.0001). Significant differences were found in the hospital mortality rate, which was the highest in the HG (13.6%) and the lowest in the LG (1.5%) (p < 0.0001). In the multiple logistic regression analysis, moderate-to-severe nutritional risk, increased age, and emergency admission were selected as significant variables for increased LOS and mortality. Further research is needed to evaluate the benefits of nutritional screening and intervention and their effect on outcomes in various disease populations.