This study investigated the effect of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, on the cecal levels of microbial metabolites of tryptophan (Trp) in rats. Rats were fed either a control diet or a...This study investigated the effect of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, on the cecal levels of microbial metabolites of tryptophan (Trp) in rats. Rats were fed either a control diet or a diet containing 0.25% (w/w) EGCG for 1 wk. The results showed that dietary EGCG treatment increased the concentration of indole-3-lactic acid while decreasing indole-3-propionic acid in the cecal contents compared to the control group. Furthermore, analysis of fecal microbial composition by 16S rRNA gene sequencing revealed that EGCG supplementation reduced the relative abundance of the genus Clostridium. This study provides fundamental insights into the role of EGCG in modulating the production of biologically active Trp metabolites.
Energy intake assessed using the food frequency questionnaire for Japanese athletes (FFQJA) was evaluated with the doubly labeled water method. The subjects (n=10) were recruited from a male track and field team in one u...Energy intake assessed using the food frequency questionnaire for Japanese athletes (FFQJA) was evaluated with the doubly labeled water method. The subjects (n=10) were recruited from a male track and field team in one university. The average total energy intake assessed using the FFQJA was 2,662 (standard deviation: 445) kcal, and the average total energy expenditure assessed using the doubly labeled water method was 3,149 (337) kcal. The FFQJA estimate of total energy intake was 486 (897) kcal lower than the total energy expenditure corrected for changes in body weight. A percentage difference between total energy intake and corrected total energy expenditure was -10.3% on average. No significant difference was found between energy intake and corrected energy expenditure. However, Kendall's τ and weighted Kappa suggested poor agreement at the individual level. Bland-Altman plot analysis suggested that there was no significant relation between differences in total energy intake and corrected total energy expenditure and average of total energy intake and corrected total energy expenditure (r=-0.493, p=0.147). Because the present study examined only a small number of participants and all of whom were male track and field athletes from the same team, future studies will be needed to clarify the generalizability of these findings.
This study aimed to evaluate sex-specific associations between food intake and frailty using cross-sectional data from 786 participants (317 men, 469 women) aged 65-101 y from the baseline survey of the Kyotango cohort s...This study aimed to evaluate sex-specific associations between food intake and frailty using cross-sectional data from 786 participants (317 men, 469 women) aged 65-101 y from the baseline survey of the Kyotango cohort study. In multivariate-adjusted models, men in the highest quartile of bean intake and vegetable intake other than green and yellow vegetables (other vegetables) had 78% and 83% lower risks of frailty, respectively, than those in the lowest quartile. Similarly, women in the highest quartile of other vegetable intake had 76% lower risks of frailty than those in the lowest quartile. Hierarchical cluster analysis revealed that Cluster 3, characterized by frequent intake of seafood, milk, and plant-based foods, including tuber vegetables, beans, green and yellow vegetables, other vegetables, and fruits, was associated with a reduced risk of frailty. In conclusion, plant-based dietary patterns were associated with a lower prevalence of frailty in men and women. Within this pattern, women consumed more seafood, suggesting a sex-specific feature of the dietary profile.
Food processing and cooking methods that involve high-temperature heating (such as roasting) alter the composition of raw food materials. Even polyphenols, which are generally considered thermally stable, undergo changes...Food processing and cooking methods that involve high-temperature heating (such as roasting) alter the composition of raw food materials. Even polyphenols, which are generally considered thermally stable, undergo changes in their chemical structure during roasting. This study investigated the roasting reaction of catechin, a functional polyphenol, at a temperature of approximately 200ºC and found that it enhanced xanthine oxidase inhibitory activity. Purification and separation of the products derived from the catechin roasting reaction revealed two types of moderately active compounds: dimeric products with a linkage between the C and A rings, and an aurone-like benzofuran product. Additionally, several fractions containing oligomeric products were identified as highly active fractions. These results suggest that catechin enhances xanthine oxidase inhibitory activity by transforming into dimeric, aurone-type, and probably oligomeric products.
This study quantified phytosterol contents in cereals, vegetables, fruits, legumes, nuts/seeds, and plant oils commonly consumed in Korea and estimated daily phytosterol intake using nationally representative dietary dat...This study quantified phytosterol contents in cereals, vegetables, fruits, legumes, nuts/seeds, and plant oils commonly consumed in Korea and estimated daily phytosterol intake using nationally representative dietary data. Phytosterol concentrations varied substantially across food groups, with the highest levels observed in plant oils (rapeseed oil, 311.63 mg/100 g; sesame oil, 302.72 mg/100 g) and seeds (sesame seeds, 159.59 mg/100 g). The average daily intake among Koreans was 84.52 mg/d. Cereals contributed 35.84 mg/d, followed by vegetables (20.40 mg/d) and oils (12.60 mg/d). Major contributors included rice (15.90 mg/d), baechu kimchi (4.60 mg/d), tofu (3.17 mg/d), and soybean oil (6.23 mg/d). In international comparisons, Korea had the lowest intake among the countries examined (China, 392.30 mg/d; Spain, 275.40 mg/d; the Netherlands, 285.00 mg/d; Finland, 238.00 mg/d; Indonesia, 223.80 mg/d; Poland, 282.97 mg/d; and the United Kingdom, 163.00 mg/d). The relatively low intake appears to reflect dietary patterns characterized by high cereal consumption and limited use of plant oils. Given that habitual intake remains far below the 2 g/d level associated with cholesterol-lowering effects, these findings provide essential baseline data for evaluating phytosterol exposure in the Korean population and for developing culturally appropriate nutritional strategies.
Thiols, as a class of organic compounds containing sulfhydryl, play important roles in antioxidant, cytoprotective and signaling activities. This study aimed to investigate thiol/disulfide metabolite homeostasis in child...Thiols, as a class of organic compounds containing sulfhydryl, play important roles in antioxidant, cytoprotective and signaling activities. This study aimed to investigate thiol/disulfide metabolite homeostasis in children with diabetic ketoacidosis (DKA) and their correlation with disease severity and renal impairment. Children with type 1 diabetes mellitus complicated with ketoacidosis from June 2022 to December 2024 were selected for this study. The metabolite levels of thiols and disulfides were measured by collecting blood samples from the children and testing them using a highly automated spectrophotometric assay. Clinical data, including blood glucose, blood ketones, blood gas analysis, and renal function indicators, were collected from the children to assess the severity of the disease and renal impairment. Seventy-two children with DKA (19 mild, 25 moderate, and 28 severe cases), were included. Native thiols were elevated with disease exacerbation, while total thiols and disulfides did not change significantly. Homeostatic index 1 and index 3 differed among the three groups. Reduced renal function was observed in 34 children with DKA, who also had decreased natural thiols, total thiol, and homeostatic index 3. Elevated native thiols were protective factors for disease exacerbation (OR 0.980, 95% CI 0.960-1.000) and renal function decline (OR 0.970, 95% CI 0.950-0.990) in children with DKA. Thiol/disulfide metabolite homeostasis in children with DKA is strongly associated with disease severity and renal impairment. Reduced native thiols are associated with more severe DKA and renal impairment.
Japanese-style diet has been reported to be associated with decreased risk of cardiovascular disease. However, no study has examined the association between a Japanese-style diet and LOX-index, which reflects the progres...Japanese-style diet has been reported to be associated with decreased risk of cardiovascular disease. However, no study has examined the association between a Japanese-style diet and LOX-index, which reflects the progression of atherosclerosis and is a predictive biomarker of cardiovascular disease. We examined the cross-sectional association between a Japanese-style diet assessed using the 12-component Japanese diet index (JDI12) score, which is a modified version of the original Japanese Diet Index, and LOX-index in Japanese municipal workers. Participants were 338 workers (166 men and 172 women aged 19-71 y) without a history of serious disease. Dietary intake was assessed using a validated brief self-administered diet history questionnaire. The JDI12 was characterized by a high intake of rice, miso soup, fish and shellfish, green and yellow vegetables, seaweeds, pickled vegetables, green tea, soybeans and soybean foods, fruits, and mushrooms and low intakes of beef and pork and coffee. LOX-index was calculated by multiplying serum concentrations of the soluble form of lectin-like oxidized LDL receptor-1 (LOX-1) by those of LOX-1 ligands containing apolipoprotein B. Multiple regression analysis was used to estimate the geometric mean of LOX-index according to tertile of JDI12 score. The JDI12 score was not associated with LOX-index after adjustment for covariates. Geometric means (95% confidence interval) of LOX-index for the lowest through highest tertile of JDI12 score were 590 (532-654), 592 (506-693), and 618 (557-687) (p for trend=0.55). Our results suggest that a Japanese-style diet as assessed by JDI12 score was not associated with LOX-index among Japanese municipal workers.Japanese-style diet has been reported to be associated with decreased risk of cardiovascular disease. However, no study has examined the association between a Japanese-style diet and LOX-index, which reflects the progression of atherosclerosis and is a predictive biomarker of cardiovascular disease. We examined the cross-sectional association between a Japanese-style diet assessed using the 12-component Japanese diet index (JDI12) score, which is a modified version of the original Japanese Diet Index, and LOX-index in Japanese municipal workers. Participants were 338 workers (166 men and 172 women aged 19-71 y) without a history of serious disease. Dietary intake was assessed using a validated brief self-administered diet history questionnaire. The JDI12 was characterized by a high intake of rice, miso soup, fish and shellfish, green and yellow vegetables, seaweeds, pickled vegetables, green tea, soybeans and soybean foods, fruits, and mushrooms and low intakes of beef and pork and coffee. LOX-index was calculated by multiplying serum concentrations of the soluble form of lectin-like oxidized LDL receptor-1 (LOX-1) by those of LOX-1 ligands containing apolipoprotein B. Multiple regression analysis was used to estimate the geometric mean of LOX-index according to tertile of JDI12 score. The JDI12 score was not associated with LOX-index after adjustment for covariates. Geometric means (95% confidence interval) of LOX-index for the lowest through highest tertile of JDI12 score were 590 (532-654), 592 (506-693), and 618 (557-687) (p for trend=0.55). Our results suggest that a Japanese-style diet as assessed by JDI12 score was not associated with LOX-index among Japanese municipal workers.
Vitamin D deficiency is mainly caused by lack of sun exposure and low intake. Data on its prevalence and optimal sun exposure in Indonesian infants, particularly aged 7-12 mo, are lacking. This randomized controlled stud...Vitamin D deficiency is mainly caused by lack of sun exposure and low intake. Data on its prevalence and optimal sun exposure in Indonesian infants, particularly aged 7-12 mo, are lacking. This randomized controlled study aimed to evaluate the effect of sun exposure on serum 25(OH)D concentration in infants in Semarang, Indonesia. Conducted between February and May 2019, the study involved 109 infants who met inclusion criteria (no congenital/chronic illness, parental consent) and excluded those with moderate to severe malnutrition, non-yellow or brown skin tone, clinically significant vitamin D deficiency, or those receiving vitamin D supplements. Intervention group received sun exposure on 50% of body surface for 5 min, three times weekly between 10:00 am and 2:00 pm for 2 mo. Serum 25(OH)D concentration were measured pre- and post-intervention, and food recall was used to assess daily intake in both groups. Pre-intervention, there was no significant difference in serum 25(OH)D concentration between intervention (mean 39.1±14.9 ng/mL) and control group (mean 38.6±15.4 ng/mL). However, post-intervention results showed a statistically significant increase in serum 25(OH)D concentration in intervention group (mean 47.9±21.9 ng/mL) compared to control group (mean 36.6±13.7 ng/mL; p=0.005). Notably, there was no significant difference in dietary vitamin D intake between two groups throughout the study. This study concluded that brief and consistent sun exposure significantly increased serum 25(OH)D concentration in infants, suggesting that sun exposure is an effective natural strategy to improve vitamin D status in this age group.
Depression is a significant public health issue affecting relationships, work, and overall quality of life. In Japan, the number of patients with mood disorders, including depression, has increased significantly in recen...Depression is a significant public health issue affecting relationships, work, and overall quality of life. In Japan, the number of patients with mood disorders, including depression, has increased significantly in recent years. Although malnutrition is known to worsen mental health and elevate the risk of depression and anxiety, the role of specific nutrients in preventing and managing depression remains unclear. This study investigated the association between nutrient intake, particularly vitamin K, and depressive symptoms, accounting for frailty in the Japanese population. Among the 607 participants in this study, 122 (20.1%) experienced depressive symptoms. Vitamin K was independently associated with depressive symptoms using a forward stepwise selection method. The relationship between vitamin K tertiles and depressive symptoms was assessed through multivariate logistic regression analysis. Adjusted for covariates (age, sex, frailty, education level, living status, exercise habits, energy intake, and alcohol consumption), the odds ratios (ORs) for depressive symptoms were significantly lower in tertile 3 compared to tertile 1. The ORs (95% confidence interval, p-value) for tertile 2 and tertile 3 were 0.64 (0.38-1.07, 0.087) and 0.48 (0.28-0.82, 0.008), respectively. Lower vitamin K intake was independently associated with depressive symptoms. Further research is necessary to confirm the role of vitamin K in preventing depressive symptoms.
The association between serum level of folate and length of hospital stay (LOS) remains unclear. Adult participants were retrospectively recruited from two teaching hospitals in Shanghai, China. Serum level of folate and...The association between serum level of folate and length of hospital stay (LOS) remains unclear. Adult participants were retrospectively recruited from two teaching hospitals in Shanghai, China. Serum level of folate and vitamin C were measured within three days after hospital admission. LOS was defined as the interval between admission and discharge. Patients were classified into tertile groups based on serum level of folate to assess the association with LOS. We further re-analyzed the association between serum level of folate and LOS under different serum level of vitamin C (also divided into tertile groups). A total number of 9,645 patients were included. Each standard deviation (SD) increase in serum level of folate was associated with 0.41 d (95% CI: -0.73 d, -0.09 d) decrease in LOS in the crude model; however, it lost significance after full adjustment. Taken the interaction effect of vitamin C into consideration, serum level of folate was inversely associated with LOS in those whose serum level of vitamin C was higher than 41.6 μmol/L. Serum level of folate was inversely associated with LOS, but the association was limited to patient with high vitamin C level.
Coronary artery disease (CAD) remains one of the leading causes of death worldwide. This study aimed to evaluate the predictive value of combining the serum to high-density lipoprotein cholesterol ratio (TG/HDL-C) with t...Coronary artery disease (CAD) remains one of the leading causes of death worldwide. This study aimed to evaluate the predictive value of combining the serum to high-density lipoprotein cholesterol ratio (TG/HDL-C) with the Controlling Nutritional Status (CONUT) score for assessing lesion severity and short-term prognosis in CAD patients. A total of 138 patients undergoing their first coronary angiography were enrolled and divided into CAD (n=88) and non-CAD (n=50) groups. Baseline characteristics and laboratory parameters were collected, and TG/HDL-C ratio and CONUT score were calculated. Lesion severity was assessed using the Gensini score, and CAD patients were followed for 6 mo. Multivariate logistic regression was performed to identify independent risk factors, evaluated the predictive performance. Both TG/HDL-C ratio (odds ratio [OR]=3.58) and CONUT score (OR=1.70) were independent predictors of CAD severity and showed significant positive correlations with Gensini scores. ROC analysis demonstrated that the combined model of TG/HDL-C and CONUT score achieved an area under the curve (AUC) of 0.86 for predicting CAD severity, outperforming individual markers. The combined model also exhibited stable predictive value for short-term prognosis (AUC=0.80). Serum TG/HDL-C ratio and CONUT score are independent and effective biomarkers for evaluating lesion severity and short-term prognosis in CAD patients. The combined predictive model enhances accuracy and may serve as a clinical tool for risk assessment and intervention decisions.
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are polyunsaturated fatty acids that are essential to human health. DHA in particular plays an important role in the development and maintenance of the brain. As...Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are polyunsaturated fatty acids that are essential to human health. DHA in particular plays an important role in the development and maintenance of the brain. As seafood consumption has decreased sharply in Japan, concerns have grown about brain growth and development in infants and school-aged children. It is therefore critical to investigate the effects of DHA/EPA intake on the brain functions of school-aged children. The International Society for the Study of Fatty Acids and Lipids has proposed the erythrocyte omega-3 index as the standard measure of omega-3 fatty acid uptake. In this pilot study, we investigated the effects of consuming a DHA-enriched milk beverage fortified with 297 mg DHA and 137 mg EPA on the erythrocyte omega-3 and stress indices in schoolchildren. Intake of the DHA-enriched milk beverage for 12 wk led to an increase in the erythrocyte omega-3 index from 6.46% to 7.67% in children aged 12 to 15 y. Moreover, it led to a significant decrease in the "helplessness" score, which is an item on the stress response scale. These results suggest that daily intake of DHA, even in low amounts, could alleviate stress in school-aged children, potentially preventing various problematic behaviors.
The purpose of this study was to evaluate changes in the indices of appetite and hunger before and after the practice among university students of the athletic club in summer and winter. The participants were 16 healthy...The purpose of this study was to evaluate changes in the indices of appetite and hunger before and after the practice among university students of the athletic club in summer and winter. The participants were 16 healthy university female students (age: 19.8±1.3 y) who were members of the university basketball team. The survey was conducted once in July and once in February (2 d total). Basketball practice was held after school on both days (around 5:00 p.m. to 8:00 p.m.). The indices of appetite and hunger were measured immediately before and after practice, 15 and 30 min after practice. The indices of appetite and hunger increased significantly after 15 min of practice in winter, and a significant high positive correlation (r=0.88, p<0.05) was found between the appetite and hunger. On the other hand, the index of hunger in summer showed no significant difference between the immediately after practice and the thereafter. Although a significant positive correlation (r=0.50, p<0.05) was found between the appetite and the hunger, the correlation coefficient was significantly lower than that in winter. No significant differences were found between the seasons for both indices. It is thought that physiological responses to energy expenditure and increased heat dissipation increased appetite and hunger after winter practice among the students. After summer practice, the appetite for cold foods increased, however, there was no significant increase in hunger due to the effect of increased water intake.
Although exercise is the most effective strategy for increasing the skeletal muscle mass, the underlying molecular mechanisms remain poorly understood. We previously demonstrated that β-carotene, a provitamin A compound,...Although exercise is the most effective strategy for increasing the skeletal muscle mass, the underlying molecular mechanisms remain poorly understood. We previously demonstrated that β-carotene, a provitamin A compound, enhances muscle mass through a retinoic acid receptor γ (RARγ)-dependent pathway. However, the involvement of vitamin A in exercise-induced muscle hypertrophy remains unclear. In this study, we used a mouse model of functional overload to mimic resistance exercise and investigated the role of vitamin A in overload-induced muscle growth. Overload increased the expression of Rdh10, Dhrs9 and Aldh1a2, an enzyme required for active vitamin A synthesis in the skeletal muscle. In contrast, the expression of Aldh1a1, Dhrs3, and Rarb was decreased by the overload. Vitamin A deficiency significantly suppressed overload-induced muscle hypertrophy and protein synthesis. Moreover, local administration of an RAR antagonist to the skeletal muscle reduced overload-induced protein synthesis. These findings suggest that vitamin A contributes to skeletal muscle hypertrophy during muscle overload by promoting protein synthesis via RAR-mediated signaling.
Extended longevity has resulted in an increased number of patients with dementia. Therefore, new methods for treating and preventing dementia are highly desirable. Multiple health benefits have been reported for Grifola...Extended longevity has resulted in an increased number of patients with dementia. Therefore, new methods for treating and preventing dementia are highly desirable. Multiple health benefits have been reported for Grifola frondosa (maitake mushrooms). In this study, we investigated the safety and effects of continuous intake of maitake mushrooms on cognitive function in healthy older individuals. We conducted a randomized, double-blind, placebo-controlled trial over 18 wk targeting 47 healthy Japanese individuals aged 60 y or older. The individuals were randomly divided into three groups: a Y10M group consumed bread containing 50 g of the maitake mushroom strain Y10M, a C5304 group consumed bread containing 50 g of the maitake mushroom strain C5304, and a placebo group consumed bread without maitake mushrooms. No participants discontinued the intervention due to adverse effects in any group. The Y10M group showed a significant improvement in cognitive assessment based on the Japanese version of the Montreal Cognitive Assessment (MoCA-J) score compared to the placebo group after the intervention. However, no difference was observed in the MoCA-J scores between the C5304 and placebo groups. The activity of natural killer cells, a type of immune cell, was also significantly augmented in the Y10M group and positively correlated with MoCA-J scores. These results suggest that improved cognitive function is, at least in part, attributable to the activation of the immune system. This study suggests that consumption of maitake mushrooms may help inhibit the decline in cognitive function in healthy older individuals.
β3 adrenergic receptor (β3AR) agonists were originally developed to overcome obesity. Administration of selective β3AR agonist CL316,243 induces lipolysis and elevates the blood concentrations of growth differentiation f...β3 adrenergic receptor (β3AR) agonists were originally developed to overcome obesity. Administration of selective β3AR agonist CL316,243 induces lipolysis and elevates the blood concentrations of growth differentiation factor 15 (GDF15), which exerts appetite-suppressing effects in mice. Liver is the main source of GDF15 in the circulation; however, it does not express β3AR. In this study, we hypothesized that free fatty acids (FFAs) released into the circulation upon lipolysis by the β3AR agonist induce GDF15 secretion from the liver. To verify this hypothesis, we manipulated the adiposity of mice using two different models, diet-induced obesity and surgical removal of white adipose tissue models, and measured the blood FFA and GDF15 levels after CL316,243 administration. Sustained elevation of blood FFA levels correlated with elevated blood GDF15 levels in the diet-induced obesity model. Conversely, surgical removal of white adipose tissue reduced the blood concentrations of FFAs and GDF15 after CL316,243 administration. Notably, CL316,243 failed to induce Gdf15 expression in AML12 mouse hepatocytes. However, FFAs induced Gdf15 expression in AML12 cells, with stearic acid acting as the most potent FFA. These data suggest that FFAs released via β3AR agonist-induced lipolysis increase Gdf15 expression levels in the liver and elevate blood GDF15 concentrations in mice. The sustained elevation of blood GDF15 levels in obese model mice by the β3AR agonist possibly reduced appetite more effectively in the obesity state than in the lean state.
To test the efficacy of heat-killed Saccharomyces cerevisiae PA YEAST SC-1 (PA YEAST SC-1) in improving the gut environment, we conducted a culture study using feces from healthy adults and a randomized double-blind plac...To test the efficacy of heat-killed Saccharomyces cerevisiae PA YEAST SC-1 (PA YEAST SC-1) in improving the gut environment, we conducted a culture study using feces from healthy adults and a randomized double-blind placebo-controlled crossover controlled trial in healthy adults. In human clinical trials, the gut microbiota was used as the primary endpoint and defecation status, fecal physicochemical tests, blood immune system tests, Constipation Assessment Scale-middle term (CAS-MT), and clinical laboratory values were measured as secondary endpoints. Culture tests showed that adding PA YEAST SC-1 substantially increased acetic acid and propionic acid levels. In a human clinical trial, PA YEAST SC-1 intake significantly increased the occupancy of short-chain fatty acid-producing bacteria (such as Parabacteroides genus), while propionic acid and the total amount of short-chain fatty acids tended to increase. Phenol, skatole, and fecal pH levels were significantly reduced. These studies indicate that PA YEAST SC-1 was utilized by the human gut bacteria and influenced the gut microbiota and metabolites, improving the gut environment.
Nicotinamide adenine dinucleotide (NAD) is an important coenzyme involved in various redox reactions. Further, NAD is a substrate for poly-ADP-ribose polymerase (PARP). DNA single-strand break (SSB) induces PARP auto-ADP...Nicotinamide adenine dinucleotide (NAD) is an important coenzyme involved in various redox reactions. Further, NAD is a substrate for poly-ADP-ribose polymerase (PARP). DNA single-strand break (SSB) induces PARP auto-ADP-ribosylation and recruits DNA repair complex. Oxidative stress, due to hydrogen peroxide (HO), generally induces SSB DNA damage and depletes NAD via PARP-mediated poly ADP-ribosylation. A low dose of HO treatment induces NAD depletion but not cell death; therefore, we used it to induce synthetic lethality. After inducing DNA damage in A549 cells, a significant decline in NAD levels was observed at 1 h after HO treatment; however, NAD levels were restored to normal levels at 24 h after the treatment. Next, we investigated how NAD was resynthesized after the treatment. In particular, the source of ribose moiety in NAD was unknown. We used a stable isotope-labeled glucose and identified that phosphoribosyl pyrophosphate (PRPP), the source of the ribose moiety in NAD, originated from glucose and not from ADP-ribose, a degradation product of auto-ADP-ribosylated PARP through NUDT5. Then, we examined whether the NAD resynthesis inhibition by glucose depletion could induce synthetic lethality with the low-dose HO treatment. HO treatment or glucose depletion did not induce cell death when used separately; however, a combination of both treatments induces the synthetic lethality in A549 cells. These results signify that a combination of oxidative stress and NAD synthesis inhibition is an optimal and minimal invasive therapeutic option to induce cell death in cancer cells.
α-Lipoic acid (LA) and coenzyme Q (CoQ) are frequently taken alone or in combination as dietary supplements with expectations of energy-stimulating effects and antioxidant actions. However, although the amino derivative...α-Lipoic acid (LA) and coenzyme Q (CoQ) are frequently taken alone or in combination as dietary supplements with expectations of energy-stimulating effects and antioxidant actions. However, although the amino derivative of LA, α-lipoamide (LA-NH), has more powerful biological activities than LA, its clinical use is limited. In the body, most of LA and CoQ are in their unstable reduced form, but the reduction mechanisms and interactions between these compounds in the body are not well-understood. Therefore, we investigated their cell-mediated-reductions and interactions between exogenous CoQ and LA or LA-NH. The reduction of exogenously added CoQ was promoted by the co-addition of LA or LA-NH only in the presence of Hep G2 cells, and this promotion was stronger with LA-NH than LA. As a mechanism, we found that exogenous LA and LA-NH were first reduced to their corresponding reduced forms mainly by thioredoxin reductase 1 and lipoamide dehydrogenase, respectively, in cells, and then the reduced forms were rapidly excreted from the cells, where they reduced extracellular CoQ to ubiquinol-10 (CoQH) non-enzymatically. Moreover, it was suggested that exogenous CoQ reduction by reduced LA-NH may also occur not only outside but also inside the cells. These results suggest that the combination of LA or LA-NH and CoQ can effectively increase the extracellular CoQH level in the body. Therefore, it is expected that their combined use will further potentiate the preventive and/or protective effects against various diseases caused by oxidative stress compared with single use, and contribute more effectively to health promotion and anti-aging.