Association of Plant-Based and High-Protein Diets with a Lower Obesity Risk Defined by Fat Mass in Middle-Aged and Elderly Persons with a High Genetic Risk of Obesity.

Obesity has become a severe public health challenge globally. The present study aimed to identify separate and interactive dietary, genetic, and other factors that increase the risk of obesity as measured by body fat (BF) mass. We utilized a genome-wide association study to identify genetic variants associated with high fat mass (obesity; n = 10,502) and combined them to generate polygenic risk scores (PRS) of genetic variants interacting with each other in adults aged over 40 while excluding body-fat-related diseases in a city-hospital-based cohort (n = 53,828). It was validated in Ansan/Ansung plus rural cohorts (n = 13,007). We then evaluated dietary and lifestyle factors in subjects to assess what factors might help overcome a genetic propensity for higher BF. The three-SNP model included brain-derived neurotrophic factor (BDNF)_rs6265, fat-mass- and obesity-associated protein (FTO)_rs1421085, and SEC16B_rs509325. The genes with the minor alleles of ADCY3_rs6545790 and BAIAP2_rs35867081 increased their gene expression in the visceral and subcutaneous adipocytes, but their gene expression decreased in the hypothalamus in eQTL analysis. In the three-SNP model, the PRS was associated with BF mass by 1.408 and 1.396 times after adjusting covariates 1 (age, gender, survey year, residence area, education, and income) and 2 (covariates in model 1 plus energy intake, alcohol intake, regular exercise, and smoking status), respectively. However, when separating subjects by PRS of the three-SNP model, a plant-based diet was the most significant factor associated with low BF, followed by high-protein diets and lower energy intakes. They could offset the effects of high genetic risk for high BF. In conclusion, modulating nutrient intakes might overcome a high genetic risk for obesity. Dietary choices favoring more plant-based and higher-protein foods might help prevent increased BF in Asians and potentially people of other ethnicities with high polygenetic risk scores.

Bioactive Components of Houttuynia cordata Thunb and Their Potential Mechanisms Against COVID-19 Using Network Pharmacology and Molecular Docking Approaches.

We investigated the molecular mechanism by which Houttuynia cordata Thunb (HCT) may intervene in coronavirus disease 2019 (COVID-19) and COVID-19-induced cytokine storms using network pharmacology and molecular docking approaches. Using the Traditional Chinese medicine Systems Pharmacology Database and Analysis Platform (TCMSP), a "component-target-pathway" topology map of HCT for COVID-19 treatment was constructed using Cytoscape. Core target genes were analyzed using the STRING database, and the signal pathway map and biological mechanism of COVID-19 therapy were obtained using cluster profilers. Active components of HCT were docked with severe respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) using AutoDockTools. Data visualization and statistical analysis were conducted using the R program. A molecular dynamic simulation was carried out with the Groningen Machine for Chemical Simulation program. HCT had six active anti-COVID-19 ingredients and 45 molecular targets. Their crucial target proteins for COVID-19 treatment were the RELA (nuclear factor kappa B [NF-κB] p65 subunit), interleukin 6, and mitogen-activated protein kinase 1. In functional enrichment analysis, the potential molecular targets of active components of HCT for COVID-19 treatment belonged to 18 signaling pathways (adjusted P = 2.12E-11). Gene ontology obtained by Kyoto Encyclopedia of Genes and Genome enrichment screening showed that the primary mechanism of COVID-19 treatment was upregulation of protein kinase C followed by downregulations of T cell differentiation and proliferation and NF-κB signaling. Molecular docking showed that the active components of HCT (quercetin and kaempferol) had similar binding affinities for SARS-CoV-2 3CLpro and SARS-CoV-2 RdRp, primary COVID-19 target proteins as did clinically used drugs. These results were confirmed with molecular dynamics simulation. In conclusion, multiple components of HCT, especially quercetin and kaempferol, have the potential to treat COVID-19 infection and COVID-19-induced cytokine storm by targeting multiple proteins.

Sarcopenia Is a Cause and Consequence of Metabolic Dysregulation in Aging Humans: Effects of Gut Dysbiosis, Glucose Dysregulation, Diet and Lifestyle.

Skeletal muscle mass plays a critical role in a healthy lifespan by helping to regulate glucose homeostasis. As seen in sarcopenia, decreased skeletal muscle mass impairs glucose homeostasis, but it may also be caused by glucose dysregulation. Gut microbiota modulates lipopolysaccharide (LPS) production, short-chain fatty acids (SCFA), and various metabolites that affect the host metabolism, including skeletal muscle tissues, and may have a role in the sarcopenia etiology. Here, we aimed to review the relationship between skeletal muscle mass, glucose homeostasis, and gut microbiota, and the effect of consuming probiotics and prebiotics on the development and pathological consequences of sarcopenia in the aging human population. This review includes discussions about the effects of glucose metabolism and gut microbiota on skeletal muscle mass and sarcopenia and the interaction of dietary intake, physical activity, and gut microbiome to influence sarcopenia through modulating the gut-muscle axis. Emerging evidence suggests that the microbiome can regulate both skeletal muscle mass and function, in part through modulating the metabolisms of short-chain fatty acids and branch-chain amino acids that might act directly on muscle in humans or indirectly through the brain and liver. Dietary factors such as fats, proteins, and indigestible carbohydrates and lifestyle interventions such as exercise, smoking, and alcohol intake can both help and hinder the putative gut-muscle axis. The evidence presented in this review suggests that loss of muscle mass and function are not an inevitable consequence of the aging process, and that dietary and lifestyle interventions may prevent or delay sarcopenia.

Protection against Alzheimer's disease by luteolin: Role of brain glucose regulation, anti-inflammatory activity, and the gut microbiota-liver-brain axis.

Luteolin is a widely distributed flavone herbs and vegetables. It has anti-oxidant and anti-inflammatory activities and improves glucose metabolism by potentiating insulin sensitivity and improving ß-cell function and mass. Alzheimer's disease (AD) is induced by the deposition of amyloid-beta (Aß) in the hippocampus and the formation of neurotoxic Aß plaques. The Aß deposition is associated with increased formation of Aß from amyloid precursor protein by up-regulation of ß-secretase and ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1). Furthermore, Aß accumulation is increased by brain insulin resistance. The impairment of insulin/IGF-1 signaling mainly in the hippocampus and brain insulin resistance is connected to signals originating in the liver and gut microbiota, known as the gut microbiota-liver-brain axis. This indicates that the changes in the production of short-chain fatty acids by the gut microbiota and pro-inflammatory cytokines can alter insulin resistance in the liver and brain. Luteolin is detected in the brain tissues after passing through the blood-brain barrier, where it can directly influence neuroinflammation and brain insulin resistance and modulate Aß deposition. Luteolin (10-70 mg/kg bw for rodents) can modulate the systemic and brain insulin resistance, and it suppresses AD development directly, and it influences Aß deposition by activation of the gut microbiota-liver-brain axis. In this review, we evaluate the potential of luteolin to mitigate two potential causes of AD, neuroinflammatory processes, and disruption of glucose metabolism in the brain. This review suggests that luteolin intake can enhance brain insulin resistance and neuroinflammation, directly and indirectly, to protect against the development of Alzheimer's-like disease, and the gut microbiota-liver-brain axis is mainly involved in the indirect pathway. However, most studies have been conducted in animal studies, and human clinical trials are needed.

Gene-gene and gene-lifestyle interactions of AKAP11, KCNMA1, PUM1, SPTBN1, and EPDR1 on osteoporosis risk in middle-aged adults.

OBJECTIVES: Osteoporosis is associated with genetic and environmental factors. The aim of this article was to determine how the polygenic risk scores (PRS) of genetic variants that affect osteoporosis and its related signaling interact with the lifestyle of middle-aged adults. METHODS: The study examined 8845 participants from Ansan/Ansung cohorts. Osteoporosis was defined as a T-score of bone mineral density ≤-2.5 in either the wrist or tibia; 1136 participants had osteoporosis. Genome-wide association studies of individuals 40 to 65 y of age were conducted and the best gene-gene interactions from the genetic variants related to osteoporosis were selected and explored using the generalized multifactor dimensionality reduction method. PRS for the best model (PRSBM) was calculated by weighted PRS that was divided into low, medium, and high groups. RESULTS: The model that contributed the most influence on osteoporosis risk with gene-gene interactions included AKAP11_rs238340, KCNMA1_ rs628948, PUM1_rs7529390, SPTBN1_ rs6752877, and EPDR1_rs2722298. The risk for osteoporosis in the tibia was elevated by 1.71-fold in the high PRSBM group compared with the low PRSBM group. Energy and nutrient intake did not have any interaction with PRSBM and thus did not influence risk for osteoporosis. However, interestingly, only coffee and caffeine intake did interact with PRSBM and affected risk for osteoporosis. In patients with low coffee (<3 cup/wk) and caffeine(<60 mg/d) consumption, osteoporosis risk was higher in the high PRSBM group than the low PRSBM group by 2.27- and 2.29-fold, respectively. In the low coffee intake group, bone mineral density in the high PRSBM group was significantly higher than in the low PRSBM arm. CONCLUSIONS: Carriers with high PRSBM increased susceptibility to osteoporosis, especially in low coffee and caffeine intake. The results can be applied to personalized nutrition for lowering the risk for osteoporosis.

Short-Term Fermented Soybeans with Bacillus amyloliquefaciens Potentiated Insulin Secretion Capacity and Improved Gut Microbiome Diversity and Intestinal Integrity To Alleviate Asian Type 2 Diabetic Symptoms.

We determined that consuming chungkookjang fermented by Bacillus subtilis (BS) or Bacillus amyloliquefaciens (BA) alleviated hyperglycemia in partially pancreatectomized (Px) rats, an Asian type 2 diabetic (T2D) animal model. Px rats had deteriorated glucose metabolism with decreased glucose-stimulated insulin secretion and insulin sensitivity. Insulin secretion capacity was improved in the ascending order of the Px-control, positive control (3 mg of metformin/kg of body weight), BS (4.5% BS diet), BA (4.5% BA diet), and normal-control (sham-operated rats). BA and BS increased ß-cell mass and decreased malondialdehyde contents and tumor necrosis factor α expression in the islets. BA increased hepatic peroxisome proliferator-activated receptor (PPAR)-α and PPAR-ß similar to the positive control. Bacillales, Lactobacillales, and Verrucomicrobiales (Akkermensia muciniphila) increased and Enterobacteriales decreased in the BA and BS compared to the Px-control. BA prevented the decrease in the villi area and the number of goblet cells in intestinal tissues. In conclusion, BA improved glucose regulation by potentiating insulin secretion and reducing insulin resistance while maintaining gut mucin contents by improving gut microbiota in lean T2D rats.

Subcutaneous fat mass is associated with genetic risk scores related to proinflammatory cytokine signaling and interact with physical activity in middle-aged obese adults.

BACKGROUND AND AIMS: Subcutaneous fat mass is negatively correlated with atherogenic risk factors, but its putative benefits remain controversial. We hypothesized that genetic variants that influence subcutaneous fat mass would modulate lipid and glucose metabolism and have interactions with lifestyles in Korean middle-aged adults with high visceral fat. MATERIALS AND METHODS: Subcutaneous fat mass was categorized by dividing the average of subscapular skin-fold thickness by BMI and its cutoff point was 1.2. Waist circumferences were used for representing visceral fat mass with Asian cutoff points. GWAS of subjects aged 40-65 years with high visceral fat (n = 3303) were conducted and the best gene-gene interactions from the genetic variants related to subcutaneous fat were selected and explored using the generalized multifactor dimensionality reduction. Genetic risk scores (GRS) were calculated by weighted GRS that was divided into low, medium and high groups. RESULTS: Subjects with high subcutaneous fat did not have dyslipidemia compared with those with low subcutaneous fat, although both subject groups had similar amounts of total fat. The best model to influence subcutaneous fat included IL17A_rs4711998, ADCY2_rs326149, ESRRG_rs4846514, CYFIP2_rs733730, TCF7L2_rs7917983, ZNF766_rs41497444 and TGFBR3_rs7526590. The odds ratio (OR) for increasing subcutaneous fat was higher by 2.232 folds in the high-GRS group, after adjusting for covariates. However, total and LDL cholesterol, triglyceride and C-reactive protein concentrations in the circulation were not associated with GRS. Subjects with high-GRS had higher serum HDL cholesterol levels than those with low-GRS. Physical activity and GRS had an interaction with subcutaneous fat. In subjects with low physical activity, the odds ratio for high subcutaneous fat increased by 2.232, but subcutaneous fat deposition was not affected in the high-GRS group with high physical activity. CONCLUSION: Obese adults with high-GRS had more subcutaneous fat, but they did not show more dyslipidemia and inflammation compared to low-GRS. High physical activity prevented subcutaneous fat deposition in subjects with high GRS for subcutaneous fat.

Moderate intake of aspartame and sucralose with meals, but not fructose, does not exacerbate energy and glucose metabolism in estrogen-deficient rats.

Both nutritive and non-nutritive sweeteners may influence energy and glucose metabolism differently. The hypothesis that sucrose, fructose, aspartame, and sucralose intake differently modulate energy and glucose metabolism was tested in an estrogen-deficient animal model. At 30 min after giving aspartame and sucralose (10 mg/kg body weight), an oral glucose tolerance test (OGTT) was conducted with glucose, sucrose, and fructose in ovariectomized (OVX) rats. After OGTT, they were continuously fed high fat diets including either 10% corn starch (Control), 10% sucrose (Sucrose), 10% fructose (Fructose), 0.05% aspartame + 9.95% starch (Aspartame) or 0.05% sucralose + 9.95% starch (Sucralose) for 8 week. During 30 min after acute administration of aspartame and sucralose, serum glucose concentrations increased despite slightly increased serum insulin levels before glucose infusion. However, glucose tolerance was not significantly different among the groups. In chronic study, serum glucose concentrations were lowest and insulin highest at the overnight-fasted state in Aspartame and Sucralose. Postprandial serum glucagon-like peptide-1 (GLP-1) and insulin levels were higher in Aspartame and Sucralose than Control. Hepatic insulin signaling (pAkt → pGSK-3ß) and phosphoenolpyruvate carboxykinase (PEPCK) expression were lower in Sucralose and Aspartame than the Fructose. Serum acetate levels produced by gut microbiota were higher were lower in the fructose group than Aspartame and Sucralose groups. In conclusion, aspartame and sucralose with a meal might be preferable sweeteners to fructose and sucrose in estrogen deficient rats, and possibly post-menopausal women; however, this needs to be confirmed in human studies.

Chronic water insufficiency induced kidney damage and energy dysregulation despite reduced food intake, which improved gut microbiota in female rats.

Water intake is recommended for weight loss, but the relationship between water intake and energy metabolism is not clear. We hypothesized that long-term water insufficiency would influence energy, glucose, and lipid metabolism while modulating gut microbiota. Female rats were provided with high-fat diets with different amounts of water and food intake for 6 weeks as follows: water provided for 1 h per day with food ad libitum (WRFA), water supply ad libitum plus pair feeding of with water restricted rats(WAFR), water restriction with ad libitum food for 3 weeks and water and food intake ad libitum for 3 weeks (WR-WA) and ad libitum supply of water and food (WAFA). Water intake in WRFA was about one-third of WAFR and WAFA, whereas food intake was lowered by 30% in WRFA and WAFR than WAFA. Body fat decreased in WRFA and WAFR, but WAFR decreased fat mass more than WRFA. Energy expenditure was lower in WRFA than WAFA and carbohydrate utilization was much higher in WRFA than the other groups. The peak serum glucose concentrations were lower in WAFA than the other groups and WRFA lowered serum insulin levels more than WAFA during OGTT. WRFA shrank the glomerulus with increased apoptotic cells and damaged renal tubules compared to the WAFA and WAFR. WR-WA also exhibited greater glomerular shrinkage and apoptosis that WAFA, but not as much WRFA, indicating that the kidneys were healing after water restriction damage. WRFA exacerbated dyslipidemia compared to the WAFA and WAFR groups. The gut microbiome was similarly modulated in WRFA and WAFR, compared to WAFA, but it was mainly affected by food intake, not water restriction in the host. WRFA and WAFR increased Bacteroidetes and decreased Firmicutes compared WAFA. In conclusion, chronic insufficient water intake induced renal damage, decreased energy expenditure, and exacerbated dyslipidemia in rats with reduced food intake. However, the reduction of food intake improved gut microbiome regardless of insufficient water intake and only minor effects on the microbiome were observed due to water restriction.

Equol Decreases Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Soy isoflavones may benefit some, but not all, menopausal women, and the ability of the women to produce equol may be the major determinant of effectiveness. We assessed the efficacy of soy isoflavones and equol for alleviating menopausal symptoms, especially vasomotor symptoms, in postmenopausal women who were equol producers and nonproducers by using systematic review and meta-analysis of randomized clinical trials (RCTs). We searched 12 English, Korean, and Chinese language scientific and medical databases. We selected all available RCTs that assessed the effect of equol, either equol itself or soy isoflavone in equol producers, on menopausal symptoms in peri- or postmenopausal women. The primary outcome was the effect on hot flashes. The severity of hot flashes was determined by the scores, and sensitivity and risk of bias analyses were conducted. Other outcomes of the review, but not meta-analysis, included depression and adverse events. Six studies (779 total subjects) met all criteria for the systematic review, 5 of those could be included in the meta-analysis (728 total subjects). Two studies included in the meta-analysis reported no statistically significant benefits of equol; the other three did report significant benefits of equol. Meta-analysis revealed a significant benefit of equol for lowering hot flash scores and revealed a generally low risk of bias. In conclusion, this study found that supplementing equol to equol nonproducers significantly lowered the incidence and/or severity of hot flashes in menopausal women.

High genetic risk scores for impaired insulin secretory capacity doubles the risk for type 2 diabetes in Asians and is exacerbated by Western-type diets.

BACKGROUND: Asians have among the highest incidence of type 2 diabetes (T2DM) in the world, partly due to low ß-cell function, causing them to rapidly develop T2DM when insulin resistant. This study tested the hypothesis that genetic polymorphisms are responsible for the low ß-cell function and that dietary factors interact with the genes to exacerbate their risk of T2DM. METHODS: We selected 10 genetic variants of 5 genes involved in insulin secretion (CDKAL1, KCNQ1, IDE, HHEX, and ABCA1) from the genome-wide association studies to calculate the genetic risk scores (GRSs) in 8842 Korean adults in the Ansan/Ansung cohort in the Korean Genome Epidemiology Study. The genetic risk score were divided into low, medium, and high groups, and the association between T2DM and the genetic risk score was measured using logistic regression. We also analysed the interaction between the genetic risk score and the nutrition intakes. RESULTS: The individual genetic variants were positively associated with T2DM even when adjusted for covariates. Individuals with medium and high genetic risk score had higher T2DM risk by 1.68 and 2.17 folds compared to those with the low genetic risk score after adjusting for covariates. The increased risk was mainly associated with lower HOMA-B, an indicator of insulin secretion capacity, but not HOMA-IR, an indicator of insulin resistance. Subjects with high carbohydrate intakes and a medium genetic risk score did not have a higher risk of T2DM, and the risk was partially mitigated in the high genetic risk score group. CONCLUSION: Seventy-two percent of the Korean population had either medium or high genetic risk scores for impaired insulin secretion, which approximately doubled their risk of type 2 diabetes, and the risk was exacerbated by consuming a low carbohydrate Western-style diets.

Efficacy and Safety of GuiZhi-ShaoYao-ZhiMu Decoction for Treating Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

OBJECTIVES: GuiZhi-ShaoYao-ZhiMu decoction (GSZD), a traditional Chinese herbal medication for the management of rheumatoid arthritis (RA), has a long history of use and modern scientific research support for efficacy, but the studies have not been systematically evaluated. Therefore, this study systematically reviewed the efficacy of GSZD using the available human clinical trials and conducted a meta-analysis. METHODS: The available databases were searched using proper languages of English, Korean, and Chinese. The key erms used for searching were "GSZD," "Cassia Twig," "Guizhi," "Paeonia lactiflora," "Shaoyao," "Anemarrhena Rhizome," "Zhimu," "rheumatoid arthritis," "randomized," "controlled trial," and "clinical trial." Randomized clinical trials (RCTs) using GSZD were included in the review and meta-analysis. According to heterogeneity, odds ratio and confidence intervals in the pooled RCTs were assessed by a fixed or random model in meta-analysis. Risk of bias was evaluated for all included studies. RESULTS: Thirteen RCTs met the inclusion criteria and were included in the meta-analysis. All studies evaluated the efficacy of GSZD for treating RA, but the herbal formulations varied since some studies added herbs to the basic GSZD formulation. However, all formulations contained the essential herbs: Guizhi, Shaoyao, and Zhimu. Each RCT included an experimental group (GSZD with or without Western-style medicine) and a control group (either standard Western-style medicines or placebo). When compared to placebo, the GSZD treatment was found to be three to six times more effective than standard Western drugs for some symptoms. Furthermore, only two studies reported any adverse events associated with the GSZD group, whereas several reported serious adverse events in the control groups. CONCLUSIONS: The Traditional Chinese Medicine, GSZD, may have equal or superior effectiveness and safety for treating RA compared to Western RA drugs. It should be considered a viable alternative to Western medicine. However, more long-term research is needed in larger patient groups to better establish its safety and efficacy.

Association of ß3-adrenergic receptor rs4994 polymorphisms with the risk of type 2 diabetes: A systematic review and meta-analysis.

AIM: The association of ADRB3 polymorphism with the risk of T2DM remains unclear perhaps due to different ethnicities and small study sizes. We systemically evaluated the association of ß3-adrenergic receptor(ADRB3)rs4994 and type 2 diabetes(T2DM) by pooling all of the case-control studies reported, and also elucidated the association according to the ethnicity and obesity of the subjects. METHODS: A literature search was conducted using PubMed, EMBASE, Cochrane Library, Korean scientific database, Chinese medical databases, and the Indian medical database to identify eligible studies for determining the association of ADRB3 rs4994 and T2DM risk. The association was examined in five genetic models: the allelic(AG), recessive(RG), dominant(DG), homozygous(HMG), and heterozygous(HTG) genetic models. Subgroup analyses stratified by ethnicity(Asians and others) were assessed. RESULTS: This meta-analysis included 17 eligible studies meeting Hardy-Weinberg equilibrium consisting of 4864 patients with T2DM(cases) and 8779 people without diabetes(controls). All models had no heterogeneity or publication bias in the meta-analysis including all subjects. ADRB3 rs4994 polymorphism of all subjects was significantly associated with an increased risk of T2DM in all genetic models with random effects: AG(OR=1.18, 95% CI: 1.05-1.32), RG(OR=1.76, 95% CI: 1.27-2.42), DG(OR=1.16, 95% CI: 1.03-1.30), HMG (OR=1.78, 95% CI: 1.25-2.52), and HTG(OR=1.11, 95% CI: 1.01-1.23). Furthermore, in sub-group analysis all models except HTG exhibited significant associations between T2DM and ADRB3 in Asians. However, the non-Asian group had no significant association in any genetic models with random effects. CONCLUSIONS: Middle-age adult Asians with the ADRB3 rs4994 minor alleles are at increased risk of T2DM.

Interaction of BDNF rs6265 variants and energy and protein intake in the risk for glucose intolerance and type 2 diabetes in middle-aged adults.

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) is associated with the risk for Alzheimer's disease and type 2 diabetes. The aim of this study was to examine the association of BDNF variants with type 2 diabetes and the interactions of different BDNF genotypes with dietary habits and food and nutrient intakes in middle-aged adults. METHODS: The study population included 8840 adults ages 40 to 65 y from the Ansan and Asung areas in the Korean Genome Epidemiology Study, a cross-sectional study of Korean adults, conducted from 2001 to 2002. Adjusted odd ratios for the prevalence of glucose intolerance and type 2 diabetes according to BDNF genotypes were calculated after adjusting for age, sex, residence area, body mass index, physical activity, and smoking and stress status. Nutrient intake was calculated from usual food intake determined by semiquantitative food frequencies using the nutrient assessment software. RESULTS: BDNF rs6265 Val/Met and Met/Met variants were negatively associated with the risk for type 2 diabetes after adjusting for covariates. Serum glucose levels after glucose loading and hemoglobin A1c, but not serum insulin levels, also were negatively associated with BDNF Val/Met and Met/Met. In subgroup analysis, sex and stress levels had an interaction with BDNF Val/Met in the risk for type 2 diabetes. Glucose-intolerant and diabetic, but not nondiabetic, patients with BDNF Met/Met had nominally, but significantly higher intakes of energy than those with BDNF Val/Val. BDNF rs6265 had consistent gene-diet interactions with energy and protein intake. With low-energy, low-protein, and high-carbohydrate intake, BDNF Val/Met lowered the risk for type 2 diabetes after adjusting for confounding factors. BDNF Val/Met did not compensate for developing type 2 diabetes with high-energy intake. Additionally, indexes of insulin resistance and insulin secretion showed the same gene-energy interaction as type 2 diabetes. CONCLUSIONS: BDNF Val/Met and Met/Met variants (rs6265) decreases the risk for glucose intolerance and type 2 diabetes. BDNF variants interacted with nutrient intake, especially energy and protein intake: Middle-aged individuals with BDNF Val/Val are prone to developing type 2 diabetes even with low energy and protein intake.

Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Although turmeric and its curcumin-enriched extracts have been used for treating arthritis, no systematic review and meta-analysis of randomized clinical trials (RCTs) have been conducted to evaluate the strength of the research. We systemically evaluated all RCTs of turmeric extracts and curcumin for treating arthritis symptoms to elucidate the efficacy of curcuma for alleviating the symptoms of arthritis. Literature searches were conducted using 12 electronic databases, including PubMed, Embase, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were "turmeric," "curcuma," "curcumin," "arthritis," and "osteoarthritis." A pain visual analogue score (PVAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used for the major outcomes of arthritis. Initial searches yielded 29 articles, of which 8 met specific selection criteria. Three among the included RCTs reported reduction of PVAS (mean difference: -2.04 [-2.85, -1.24]) with turmeric/curcumin in comparison with placebo (P < .00001), whereas meta-analysis of four studies showed a decrease of WOMAC with turmeric/curcumin treatment (mean difference: -15.36 [-26.9, -3.77]; P = .009). Furthermore, there was no significant mean difference in PVAS between turmeric/curcumin and pain medicine in meta-analysis of five studies. Eight RCTs included in the review exhibited low to moderate risk of bias. There was no publication bias in the meta-analysis. In conclusion, these RCTs provide scientific evidence that supports the efficacy of turmeric extract (about 1000 mg/day of curcumin) in the treatment of arthritis. However, the total number of RCTs included in the analysis, the total sample size, and the methodological quality of the primary studies were not sufficient to draw definitive conclusions. Thus, more rigorous and larger studies are needed to confirm the therapeutic efficacy of turmeric for arthritis.

Interactions with the MC4R rs17782313 variant, mental stress and energy intake and the risk of obesity in Genome Epidemiology Study.

BACKGROUND: The melanocortin-4 receptor (MC4R) regulates metabolism by modulating eating behavior and MC4R variants (rs17782313 and rs571312) are associated with obesity in Asians and Caucasians. However, the impact of their interactions with nutritional and lifestyle factors on obesity are poorly described. Therefore, we investigated the interaction of MC4R variants and dietary patterns on the risk of obesity in Korean middle-aged adults. METHODS: Data collected included, genetic variations, anthropometric and biochemical measurements, dietary and lifestyle habits, and food intake. Data were obtained from the 8830 adults aged 40-69 years in the Ansung and Ansan cohort of the Korean Genome Epidemiology Study. RESULTS: The MC4R rs18882313 minor allele had a higher frequency in the obese group (P < 0.01). MC4R genotypes were not associated with differences in daily energy and macronutrient intakes. However, the intakes of processed foods and fat (as percentages of energy) were significantly higher and intake of fruits were significantly lower in subjects with MC4R minor alleles (P < 0.05). Interestingly, there was a positive interaction between MC4R variants and mental stress levels that were associated with the risk of obesity after adjusting for age, gender, residence area, daily energy intake, smoking status and physical activity (interaction P = 0.0384). Only in subjects with high stress were MC4R minor alleles associated with higher BMIs after adjusting for confounders. The association was present without modulating energy and nutrient intake. In the group with energy intakes higher than estimated energy requirement (EER), subjects with MC4R minor alleles had higher BMIs than those with the major alleles (P < 0.001). CONCLUSIONS: The interactions of mental stress and energy intakes with the MC4R minor allele genotype might be associated with increased risk of obesity in Korean adults. This research might identify subjects with a specific MC4R minor alleles as a human subset of people with a low metabolic tolerance for excessive energy intake, especially when under stress.

Efficacy of Ginger for Alleviating the Symptoms of Primary Dysmenorrhea: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

OBJECTIVE: There has been no attempt to date to synthesize the available evidence for the efficacy of ginger for treating primary dysmenorrhea. This systematic review evaluates the current evidence for the effectiveness of ginger for treating primary dysmenorrhea. METHODS: Literature searches were conducted using 12 electronic databases including PubMed, EMBASE, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were: "ginger" or "Zingiber officinale" and "dysmenorrhea" and "pain." Studies using ginger as a treatment of primary dysmenorrhea were considered for inclusion. The major outcome of primary dysmenorrhea was assessed using a pain visual analogue score (PVAS). RESULTS: Initial searches yielded 29 articles. Of these original results, seven met specific selection criteria. Four of the RCTs compared the therapeutic efficacy of ginger with a placebo during the first 3-4 days of the menstrual cycle and were included in the meta analysis. The meta-analysis of these data showed a significant effect of ginger in reducing PVAS in subjects having primary dysmenorrhea (risk ratio, -1.85; 95% CI of -2.87, -0.84, P = 0.0003). Six RCTs out of 7 exhibited low to moderate of risk of bias. CONCLUSION: Collectively these RCTs provide suggestive evidence for the effectiveness of 750-2000 mg ginger powder during the first 3-4 days of menstrual cycle for primary dysmenorrhea.

Red peppers with moderate and severe pungency prevent the memory deficit and hepatic insulin resistance in diabetic rats with Alzheimer's disease.

BACKGROUND: Dementia induced by ß-amyloid accumulation impairs peripheral glucose homeostasis, but red pepper extract improves glucose homeostasis. We therefore evaluated whether long-term oral consumption of different red pepper extracts improves cognitive dysfunction and glucose homeostasis in type 2 diabetic rats with ß-amyloid-induced dementia. METHODS: Male diabetic rats received hippocampal CA1 infusions of ß-amyloid (25-35) (AD) or ß-amyloid (35-25, non-plaque forming), at a rate of 3.6 nmol/day for 14 days (Non-AD). AD rats were divided into four dietary groups receiving either 1% lyophilized 70% ethanol extracts of either low, moderate and severe pungency red peppers (AD-LP, AD-MP, and AD-SP) or 1% dextrin (AD-CON) in Western diets (43% energy as fat). RESULTS: The ascending order of control < LSP < MSP and SSP potentiated the phosphorylation of CREB and GSK and inhibited Tau phosphorylation in the hippocampus which in turn inhibited ß-amyloid accumulation. The inhibition by MP and SP reduced the memory deficit measured by passive avoidance test and water maze test. Furthermore, the accumulation of ß-amyloid induced glucose intolerance, although serum insulin levels were elevated during the late phase of oral glucose tolerance test (OGTT). All of the red pepper extracts prevented the glucose intolerance in AD rats. Consistent with OGTT results, during euglycemic hyperinulinemic clamp glucose infusion rates were lower in AD-CON than Non-AD-CON with no difference in whole body glucose uptake. Hepatic glucose output at the hyperinsulinemic state was increased in AD-CON. ß-amyloid accumulation exacerbated hepatic insulin resistance, but all red pepper extract treatments reversed the insulin resistance in AD rats. CONCLUSIONS: The extracts of moderate and severe red peppers were found to prevent the memory deficit and exacerbation of insulin resistance by blocking tau phosphorylation and ß-amyloid accumulation in diabetic rats with experimentally induced Alzheimer's-like dementia. These results suggest that red pepper consumption might be an effective intervention for preventing age-related memory deficit.