Breast cancer is one of the most common malignancies in women worldwide and is associated with a variety of risk factors. Folate and vitamin B₁₂ are key elements of the one-carbon metabolism pathway where methylenetetrahydrofolate reductase (MTHFR) plays a significant role. Though many molecular and epidemiological studies have been performed to explore the relationship between intake folate, vitamin B₁₂, MTHFR gene polymorphism and breast cancer risk, there is no consensus to date. By reviewing the relevant literatures and summarizing the potential effect of dietary folate intake on MTHFR genes polymorphism and breast cancer risk, we conclude that MTHFR C677T gene polymorphism is associated with breast cancer risk among Asian, but not Caucasians, and the MTHFR A1298C gene polymorphism is not a susceptibility factor of breast cancers. Concomitant low activity of MTHFR enzyme resulted from C677T gene polymorphism and low dietary folate intake is associated with increased breast cancer risk.

Cardiovascular disease (CVD) is the leading cause of death globally, except Africa, and poses a severe health burden worldwide. Both in vitro and in vivo studies have demonstrated the protective effects of myricetin for preventing CVD. For this review, we have assessed the literature from 2009 to 2019 at home and abroad to uncover the protective roles of myricetin for preventing CVD. Myricetin exhibits cardioprotective, anti-hypertensive, anti-atherosclerotic, anti-hyperglycemic, and anti-hyperlipidemic effects. In addition, myricetin may alleviate some of the complications caused by adult-onset diabetes. The combined functions of myricetin allow for the prevention of CVD. This review describes the possible therapeutic benefits of myricetin, along with its potential mechanisms of action, to support the clinical use of the myricetin for the prevention of CVD.

The aim of this study was to investigate the association of serum 25-hydroxyvitamin D (25(OH)D) with skeletal muscle mass (SMM) and grip strength in patients on peritoneal dialysis. In this single center retrospective study, a total of 113 incident peritoneal dialysis patients (65 men, 48 women) were included. Serum concentrations of 25(OH)D were measured through radioimmunoassay. Hypovitaminosis was classified when the level of serum 25(OH)D was <20 ng/mL. SMM was assessed through bioelectrical impendence analysis, whereas grip strength was assessed through handgrip dynamometer. On the basis of expert consensus of the Asian Working Group for Sarcopenia, low muscle mass was defined as relative skeletal mass index (RSMI)<7.0 kg/m² for men and <5.7 kg/m² for women. The general linear and noncondition logistical regression model were employed to explore the association between vitamin D and both muscle mass and grip strength. The mean serum 25(OH)D level was 19.3(±8.4) ng/mL. Compared with 25(OH)D<20 ng/mL, the mean values of SMM, appendicular skeletal muscle mass (ASM), ASMI, and grip strength were higher for ≥20 ng/mL. Subjects (25(OH)D<20 ng/mL) had a greater proportion of low SMM (55.8%) and low grip strength (66.4%). After adjusting for multiple factors, serum 25(OH)D was positively associated with grip strength (β=0.18, p=0.009), ASM (β=0.14, p<0.001), and RSMI (β=0.07, p<0.001); 25(OH)D<20 ng/mL was significantly associated with low grip strength (OR=2.97, 95% CI: 1.17-7.55), and low SMM (OR=2.73, 95% CI: 1.15-6.45). The present study demonstrated a positive association between serum vitamin D status and skeletal muscle mass and grip strength in patients on peritoneal dialysis.

Calcium supplements were necessary for those people with low calcium intake and high risk of osteoporosis. Recent cohort studies have shown that long-term calcium supplements may raise the risk of cardiovascular disease, but its mechanism is still unclear. In this study, metabonomics were employed to evaluate the changes of metabolism in rats with long-term calcium supplementation and further seek the potential markers of cardiovascular risk. SD rats were divided into two groups including normal control group (calcium intake, 0.50 g/kg bw) and high calcium supplement group (calcium intake, 2.50 g/kg bw). After 6 mo, the cardiovascular system and bone mineral density were observed. UPLC-MS was used to analyze serum metabonomics in rats. The results showed that the contents of total cholesterol and low-density lipoprotein cholesterol in the high calcium group were significantly higher than those in normal control group (p<0.05). The interventricular septum thickness (IVS), left ventricular mass (LVM), left ventricular posterior wall thickness (LVPW) in the high calcium group were higher than those in normal control group (p<0.05). Serum metabonomics analysis showed that there were persistent changes in many metabolites such as sphingosine and its derivatives (p<0.01) in the comparison between the high calcium group and the normal group. These results indicated that long term calcium supplementation can lead to dyslipidemia in rats, such as the rise of cholesterol and low-density lipoprotein, which might induce myocardial hypertrophy. Long-term calcium supplementation can cause the changes of the amount of sphingosine and its derivatives in the body, which many have potential risk to cardiovascular diseases such as myocardial hypertrophy and atherosclerosis.

Exercise can improve obesity and metabolic disorders in mice fed a high-fat diet (HFD), but the role of AMPKα2 in the process remains unclear. The aim of this study was to investigate the role of AMPKα2 in the exercise-induced improvements in glucose tolerance and metabolic turnover in obesity mice. Male wild-type mice (n=12) and AMPKα2 knockout (AMPKα2 KO) mice (n=12) were fed a HFD for 16 wk and were then randomly divided into four groups: WT HFD group (WT HF), AMPKα2 KO HFD group (AMPKα2 KO HF), WT HFD exercise group (WT HE), and AMPK HFD exercise group (AMPKα2 KO HE). The HF groups continue to be fed a HFD from 16 wk to 24 wk, and the HE groups were fed a HFD and performed exercise training. After 8 wk of exercise, all mice were placed in an energy metabolism chamber to test their metabolic turnover, include locomotor activity, food intake, oxygen consumption (VO₂), carbon dioxide production (VCO₂), energy expenditure (EE) and respiratory exchange ratio (RER), over a period of 3 d. Exercise improved glucose tolerance, VO₂, VCO₂ and EE in mice fed a HFD (p<0.05). The VO₂, VCO₂ and EE in AMPKα2 KO HE group were lower than these in WT HE group (p<0.05). Our findings revealed exercise improved glucose tolerance and metabolic disorders in C57 and AMPKα2 KO mice fed a HFD. AMPKα2 is not essential for exercise-induced improvements in glucose tolerance and metabolic disorders.

Diarrhea is the most common complication of enteral nutrition (EN). Pro/prebiotics are typically used to prevent diarrhea during EN. This study aimed to demonstrate the effects of enteral formula containing fermented dairy products (FDPs) and galacto-oligosaccharides on intestinal mucosal functions in rats. After feeding rats with regular rodent chow (RRC), standard formula (STD-F), and FDP-containing formula (FDP-F) for 2 wk, the rats were sacrificed with their intestines removed. Then, the electrophysiological properties of intestinal epithelia were measured using the Ussing chamber. In addition, organic acids and microbiota in the cecal contents were analyzed. In FDP-F-fed rats, electrical nerve activation-evoked increase in short-circuit current (I_sc) in the cecum and middle colon was reduced compared with STD-F-fed rats. Mucosal propionate-evoked changes in I_sc in FDP-F-fed rats were also reduced in the terminal ileum. The total cecal organic acid concentration in STD-F-fed rats decreased compared with RRC-fed rats, and approximately half was recovered in FDP-F-fed rats, which contributed to the recovery of acetate and butyrate concentrations. In microbiota analysis, the density of total bacteria, particularly Bifidobacterium, in cecal contents increased in FDP-F-fed rats. In conclusion, the consumption of FDP-F changed the total amounts and components of gut microbiota and organic acids, and resulted in inhibitory changes in mucosal luminal stimulant- and nervous system-mediated fluid secretory function. These findings suggest that FDP-F might prevent the incidence of diarrhea during EN.

Tryptophan (TRP), a precursor of serotonin is believed to have an antidepressant effect. The pathway for brain uptake of TRP is shared by other large neutral amino acids; therefore, the best time to take TRP may be between meals. No previous study has, however, designated the time of TRP dosing to improve mood. Further, the effects of TRP on autonomic nervous system (ANS) activity are unclear. This study investigated the effects of TRP, vitamin B₆, and nicotinamide-containing supplements loading between meals on mood and ANS activity in depressive young adults. Thirty depressive young adults were randomly allocated to receive TRP, vitamin B₆, and nicotinamide-containing supplements or a placebo supplements twice daily between meals for 7 d. Mood was measured using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Profile of Mood States (POMS). ANS activities were analyzed by heart rate variability power spectral analysis. Blood samples were assayed for plasma total TRP concentration. For analysis, TRP and placebo groups were further classified into two subgroups according to CES-D score (mild to moderate vs. severe depressive symptoms). The CES-D score significantly improved following both treatments in the severe depression subgroups, while the POMS depression score was significantly improved only in the TRP severe depression subgroup. There was no significant change in ANS activity or plasma total TRP in any group. TRP, vitamin B₆, and nicotinamide-containing supplements loading between meals can quickly improve depressed mood in quite low dose in young adults with severe subclinical depression.

Previous studies suggest that circulating fibroblast growth factor 21 (FGF21) levels are elevated in patients with fatty liver, while fasting-induced secretion of FGF21 is lower in obese patients. It has been reported that soy protein prevents hepatic fat accumulation and induces FGF21 secretion. The present study was designed to evaluate the response of circulating FGF21 levels to feeding and fasting in mice fed soy protein-rich diets. For this, C57BL/6J mice were distributed into control, high-fat high-sucrose (HFHS)-casein protein, HFHS-soy protein, and HFHS-β-conglycinin diet groups. Plasma samples were collected after 10 and 11 wk either in dark periods with feeding conditions or light periods under fasting conditions using a crossover design. After a 12-wk period of feeding, HFHS-induced hepatic fat accumulation was significantly reduced in the groups fed HFHS-soy protein and HFHS-β-conglycinin as compared to that in the HFHS-casein-fed group (p<0.05). Plasma FGF21 concentration was significantly higher in the dark/feeding periods in the HFHS-casein group (p<0.05), while in the HFHS-β-conglycinin group it was higher in the light/fasting periods (p<0.05). The amount of mesenteric fat was significantly lower in the HFHS-β-conglycinin group than in the HFHS-casein and HFHS-soy protein groups (p<0.01). The fasting-induced FGF21 secretion was significantly and negatively correlated with hepatic fat content (p<0.05). The present study revealed that hepatic fat accumulation was associated with lower fasting-induced FGF21 secretion, which was regulated better by dietary intake of soy protein. These results support the preventive effects of soy protein on central obesity.

Pentosidine is the most well-characterized advanced glycation end product (AGE). It has been measured by HPLC, although this approach cannot be adapted to analyze many clinical samples and is also time-consuming. Furthermore, the detection of pentosidine using a reported ELISA kit and HPLC system requires pretreatment by heating, which generates artificial pentosidine leading to overestimation. We developed a novel pentosidine ELISA system that don’t require sample pretreatment for analyzing urine samples. We then analyzed the accuracy, precision, and reliability of this system. Urinary samples for analysis were obtained from healthy volunteers and stored urinary samples from the participants of the Nagano cohort study were also used. The LoB and LoD were 4.25 and 6.24 pmol/mL, respectively. Intra- and inter-assay coefficients of variation were less than 5%. The spiking and dilution recoveries were 101.4% and 100.5%, respectively. Analysis of the cross-reactivities against seven compounds representative of AGEs and structurally similar to pentosidine showed no significant cross-reactivity. The correlation coefficient between the concentrations of pentosidine obtained from HPLC and ELISA for the same urine samples was r=0.815. The urinary excretion of pentosidine upon overnight fasting was lower than that after a meal, suggesting the presence of diurnal variation in urinary pentosidine. In contrast, day-to-day variation was not observed. These results indicate that the ELISA system has sufficient reliability, accuracy, and precision for measuring urinary pentosidine. Sampling of fasting urine is suitable for minimizing variation. In conclusion, this ELISA system is promising to evaluate the effect of AGE on lifestyle-related diseases.

Impaired glucose tolerance (IGT) induces chronic inflammation and subsequent development of complications triggered by arteriosclerosis. Moreover, undernutrition in pregnant rodents can induce IGT in their offspring. Here, we assessed whether undernutrition in pregnant rats would induce chronic inflammation in their offspring by measuring the expression levels of inflammation-related genes in peripheral blood leukocytes. Pregnant Wistar rats were divided into two groups: the control group received an American Institute of Nutrition Rodent diet (AIN-93G) ad libitum, and the undernutrition group had their diet restricted by 50% (w/w) compared with the control group from day 10 of pregnancy until birth of the offspring. Subsequently, mothers and pups were allowed to access the AIN-93G diet freely. At day 35 after birth, male pups were fasted for 4 h and subsequently orally administered with glucose solution (2 g/kg body weight). Blood glucose area under the curve (AUC) after glucose loading was significantly greater in the undernutrition group than the control group. The mRNA levels for inflammatory cytokines were increased by glucose loading especially in the undernutrition group. Expressions of genes encoding S100A9 and cell adhesion molecule CD11b were increased by glucose loading in the undernutrition group. Thus, undernutrition of pregnant rats during mid to late gestation induced the expression of inflammation-related genes in peripheral blood leukocytes of their offspring, with the development of IGT and impaired insulin secretion.

The absorption of vitamin B₁₂ is a complex process involving gastric acid and intrinsic factor as the indispensable components. In this study, we have investigated the effects of the administration site in enteral feeding on vitamin B₁₂ status in subjects with severe motor and intellectual disabilities (SMID). This is a cross-sectional study conducted from January to June 2016. Blood concentrations of vitamin B₁₂, folate, vitamin B₆, and homocysteine (Hcy) were measured in a total of 82 subjects (38 men, 44 women). Also, nutrients intake was assessed. Subjects with enteral feeding (EF) had significantly higher intakes of vitamin B₁₂, folate, and vitamin B₆ than those with oral ingestion (OI). Serum folate and vitamin B₆ concentrations in subjects with EF were significantly higher than those with OI. Among the EF subjects, serum vitamin B₁₂ concentration was significantly higher in those fed with gastric tube than those fed with jejunal tube in spite of similar vitamin B₁₂ intakes. No significant difference was observed between the two groups regarding the circulating concentrations of folate, vitamin B₆, or Hcy. Although each administration route has its own benefit, gastric tube is advantageous in the absorption of vitamin B₁₂.

This study investigated the effect of various concentrations of pteroyl-mono-γ-glutamate (PteGlu₁) and pteroyl-di-γ-glutamate (PteGlu₂) on the growth of Lactobacillus rhamnosus strains ATCC 7469 (wild-type strain) and ATCC 27773 (chloramphenicol-resistant strain) used for folate microbiological assays. At concentrations of 0.025-0.20 nmol/L, the growth of the chloramphenicol-resistant strain was stimulated to a greater extent by PteGlu₁ than by PteGlu₂, but the wild-type strain did not show such phenomena. L. rhamnosus ATCC 27773 bioassays were used to determine the total folate content of various foods treated with a chicken pancreas folate conjugase. This showed a significantly lower value when PteGlu₁ was used as a calibrator than with PteGlu₂. These results indicated that PteGlu₂ should be the standard folate compound when chicken pancreas folate conjugase is used in preparing samples for L. rhamnosus ATCC 27773 bioassay.