Saengmaeksan, a traditional polyherbal formulation containing Panax ginseng, improves energy metabolism during exercise.

Saengmaeksan (SMS), a representative oriental medicine that contains Panax ginseng Meyer, Liriope muscari, and Schisandra chinensis (1:2:1), is used to improve body vitality and enhance physical activity. However, there is limited scientific evidence to validate the benefits of SMS. Here, we investigated the in vitro and in vivo regulatory effects of SMS and its constituents on energy metabolism and the underlying molecular mechanisms. For this, quantitative real-time polymerase chain reaction, 3D holotomographic microscopy, western blotting, and glucose uptake experiments using 18F-fluoro-2-deoxy-D-glucose (18F-FDG) were performed using L6 cells to investigate in vitro energy metabolism changes. In addition, 18F-fluorocholine (18F-FCH) and 18F-FDG positron emission tomography/computed tomography (PET/CT) analyses, immunohistochemistry, and respiratory gas analysis were performed in mice post-endurance exercise on a treadmill. In the energy metabolism of L6 cells, a significant reversal in glucose uptake was observed in the SMS-treated group, as opposed to an increase in uptake over time compared to the untreated control group. Furthermore, P. ginseng alone and SMS significantly decreased the volume of lipid droplets. SMS also regulated the phosphorylation of extracellular signal-regulated kinase (ERK), phosphorylation of p38, mitochondrial morphology, and the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE/Ref-1) in H2O2-stimulated L6 cells. In addition, SMS treatment was found to regulate whole body and muscle energy metabolism in rats subjected to high-intensity exercise, as well as glucose and lipid metabolism in skeletal muscle. Therefore, SMS containing P. ginseng ameliorated imbalanced energy metabolism through oxidative stress-induced APE/Ref-1 expression. SMS may be a promising supplemental option for metabolic performance.

Vitamin C and glutathione supplementation: a review of their additive effects on exercise performance.

PURPOSE: This review aimed to investigate the effects of vitamin C and glutathione supplementation on exercise performance. METHODS: We conducted a literature search across the PubMed, Google Scholar, and Web of Science databases using the keywords vitamin C, glutathione, antioxidants, exercise, and oxidative stress. RESULTS: The effects of vitamin C supplementation on exercise performance and oxidative stress levels are inconsistent. Glutathione, with its diverse forms of supplementation and methods, presents mixed outcomes. Vitamin C and glutathione have deeply interconnected antioxidant functions and are mutually essential to each other. Research investigating the combined intake of these two substances, which are intricately linked biochemically, and their effects on exercise performance remain largely unexplored. CONCLUSION: Studies on the effects of vitamin C and glutathione intake on exercise have been conducted using diverse approaches; however, the results have not been consistent. Although an additive effect is anticipated with the combined intake of vitamin C and glutathione, research on this topic is currently insufficient, and further studies are required.

Enhancing Supplemental Effects of Acute Natural Antioxidant Derived from Yeast Fermentation and Vitamin C on Sports Performance in Triathlon Athletes: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Trial.

This study investigated the acute effects of natural antioxidants, derived from yeast fermentation containing glutathione and dietary vitamin C supplementation, on metabolic function, skeletal muscle oxygenation, cardiac function, and antioxidant function during submaximal exercise in middle-aged triathlon athletes. Twelve participants (aged 49.42 ± 5.9 years) completed 90 min submaximal cycling trials corresponding to 70% maximal oxygen uptake with either vitamin C and glutathione (VitC+Glu), vitamin C (VitC), glutathione (Glu) supplementation, or placebo. Metabolic function (minute ventilation, oxygen uptake, carbon dioxide output [VCO2], respiratory exchange ratio [RER], oxygen pulse [O2pulse], carbohydrate oxidation, fat oxidation, and energy expenditure), skeletal muscle oxygenation (oxidized hemoglobin and myoglobin in skeletal muscle tissue, total hemoglobin and myoglobin in skeletal muscle tissue [tHb]), cardiac function (heart rate [HR], stroke volume [SV], cardiac output, end-diastolic volume, end-systolic volume, and ejection fraction), and antioxidant function parameters (blood lactate, superoxide dismutase, catalase, glutathione peroxidases, glutathione [GSH], diacron reactive oxygen metabolite [dROM], and biological antioxidant potential [BAP]) were measured during submaximal exercise and recovery. VCO2, RER, HR, blood lactate after exercise, and dROM were significantly lower, and O2pulse, tHb, and BAP were significantly higher for VitC+Glu than for the other trials (p < 0.05). In conclusion, combined vitamin C and glutathione supplementation was more effective in improving metabolic function, skeletal oxygenation, cardiac function, and antioxidant function during prolonged submaximal exercise in middle-aged triathletes.

Dietary Arginine and Citrulline Supplements for Cardiovascular Health and Athletic Performance: A Narrative Review.

The global market for nutritional supplements (NS) is growing rapidly, and the use of L-arginine (Arg), L-citrulline (Cit), and citrulline malate (CitMal) supplements has been shown to enhance cardiovascular health and athletic performance. Over the past decade, Arg, Cit, and CitMal supplements have received considerable attention from researchers in the field of exercise nutrition, who have investigated their potential effects on hemodynamic function, endothelial function, aerobic and anaerobic capacity, strength, power, and endurance. Previous studies were reviewed to determine the potential impact of Arg, Cit, and CitMal supplements on cardiovascular health and exercise performance. By synthesizing the existing literature, the study aimed to provide insight into the possible uses and limitations of these supplements for these purposes. The results showed that both recreational and trained athletes did not see improved physical performance or increased nitric oxide (NO) synthesis with 0.075 g or 6 g doses of Arg supplement per body weight. However, 2.4 to 6 g of Cit per day for 7 to 16 days of various NSs had a positive impact, increasing NO synthesis, enhancing athletic performance indicators, and reducing feelings of exertion. The effects of an 8 g acute dose of CitMal supplement were inconsistent, and more research is needed to determine its impact on muscle endurance performance. Based on the positive effects reported in previous studies, further testing is warranted in various populations that may benefit from nutritional supplements, including aerobic and anaerobic athletes, resistance-trained individuals, elderly people, and clinical populations, to determine the impact of different doses, timing of ingestion, and long-term and acute effects of Arg, Cit, and CitMal supplements on cardiovascular health and athletic performance.

Capsiate Intake with Exercise Training Additively Reduces Fat Deposition in Mice on a High-Fat Diet, but Not without Exercise Training.

While exercise training (ET) is an efficient strategy to manage obesity, it is recommended with a dietary plan to maximize the antiobesity functions owing to a compensational increase in energy intake. Capsiate is a notable bioactive compound for managing obesity owing to its capacity to increase energy expenditure. We aimed to examine whether the antiobesity effects of ET can be further enhanced by capsiate intake (CI) and determine its effects on resting energy expenditure and metabolic molecules. Mice were randomly divided into four groups (n = 8 per group) and fed high-fat diet. Mild-intensity treadmill ET was conducted five times/week; capsiate (10 mg/kg) was orally administered daily. After 8 weeks, resting metabolic rate and metabolic molecules were analyzed. ET with CI additively reduced the abdominal fat rate by 18% and solely upregulated beta-3-adrenoceptors in adipose tissue (p = 0.013) but did not affect the metabolic molecules in skeletal muscles. Surprisingly, CI without ET significantly increased the abdominal fat rate (p = 0.001) and reduced energy expenditure by 9%. Therefore, capsiate could be a candidate compound for maximizing the antiobesity effects of ET by upregulating beta-3-adrenoceptors in adipose tissue, but CI without ET may not be beneficial in managing obesity.

The Effect of a 2-Week Red Ginseng Supplementation on Food Efficiency and Energy Metabolism in Mice.

Red ginseng (RG) ingestion reportedly affects body weight, food intake, and fat accumulation reduction. It also induces changes in energy metabolism regulation and glycemic control. Previously, 2-week RG ingestion with endurance training was found to enhance fat oxidation during exercise. However, such effects on energy metabolism and the expression of mRNAs related to energy substrate utilization in resting mice (untrained mice) are still unclear. Here, we determined the effect of RG on energy metabolism and substrate utilization in untrained male mice. Twenty-four mice were separated into an RG group that received a daily dosage of 1 g/kg RG for 2 weeks, and a control (CON). Energy expenditure, blood and tissue glycogen levels, and expression of mRNAs related to energy substrate utilization in muscles were measured before and 2 weeks after treatment. Total food intake was significantly lower in the RG than in the CON group (p < 0.05), but final body weights did not differ. Carbohydrate and fat oxidation over 24 h did not change in either group. There were no significant differences in gastrocnemius GLUT4, MCT1, MCT4, FAT/CD36, and CPT1b mRNA levels between groups. Thus, the effects of RG ingested during rest differ from the effects of RG ingestion in combination with endurance exercise; administering RG to untrained mice for 2 weeks did not change body weight and energy metabolism. Therefore, future studies should consider examining the RG ingestion period and dosage for body weight control and improving energy metabolism.

Dietary Factors and Eating Behaviors Affecting Diet-Induced Thermogenesis in Obese Individuals: A Systematic Review.

Obese individuals are considered to have lower energy expenditure (EE) rates than non-obese individuals. We aimed to investigate the effects of various factors related to food intake on diet-induced thermogenesis (DIT) in the EE of obese individuals. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed relevant literature from PubMed, Embase, and Medline databases from study inception till the end of July 2019. Studies on dietary factors affecting DIT in obese individuals were included. Fifteen studies were included; these studies assessed macronutrient, single-nutrient, or supplement meal compositions, as well as dietary patterns and behaviors. The effect of obesity on DIT was not constant in each study. Differences in DIT pertained to the protein ratio being higher than the fat ratio or the carbohydrate ratio being higher than the fat ratio. High intake of calcium and vitamin D as well as high-oleic peanut supplements increased DIT in obese people. In addition, ascorbic acid intake, fatty acid saturation, and the chain length of various fatty acids had no effects on DIT. In conclusion, the findings suggest that in obese individuals, DIT is associated with various factors related to meal, nutrient, and dietary habits. However, because of the complexity of the relationship between DIT and obesity, it is difficult to determine the critical element underlying this association.

Effect of Korean Magnolia obovata Extract on Platelet-Derived Growth Factor-Induced Vascular Smooth Muscle Cells.

OBJECTIVE: To investigate the effects of Korean Magnolia obovata crude extract (KME) on plateletderived growth factor (PDGF)-BB-induced proliferation and migration of vascular smooth muscle cells (VSMCs). METHODS: KME composition was analyzed by high-performance liquid chromatography (HPLC). VSMCs were isolated from the aorta of a Sprague-Dawley rat, incubated in serum free-Dulbecco's modified Eagle's medium in the presence or absence of KME (10, 30, 100, and 300 µg/mL), then further treated with PDGF-BB (10 ng/mL). VSMC proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and VSMC migration was determined using the Boyden chamber and scratch wound healing assays. Western blot analysis was used to detect phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (p-ERK1/2), protein kinase B (p-Akt), and stress-activated protein kinase/c-Jun NH2-terminal kinase (p-SAPK/JNK). The antimigration and proliferation effects of KME were tested using aortic sprout outgrowth. RESULTS: The HPLC analysis identified honokiol (0.45 mg/g) and magnolol (0.34 mg/g) as the major components of KME. KME (30, 100, and 300 µg/mL) significantly decreased the proliferation and migration of PDGF-BB-stimulated (10 ng/mL) VSMCs and the PDGF-BB-induced phosphorylation of EKR1/2, Akt, and SAPK/JNK (P<0.05). Furthermore, PDGF-BBinduced VSMCs treated with 300 µg/mL of KME showed reduction in aortic sprout outgrowth. CONCLUSION: KME could inhibit abnormal proliferation and migration of VSMCs by down-regulating the phosphorylation of EKR1/2 and Akt. Thus, KME might be a functional food for preventing vascular disorders.

Changes in the Paradigm of Traditional Exercise in Obesity Therapy and Application of a New Exercise Modality: A Narrative Review Article.

BACKGROUND: Obesity is recognized as an important global health problem that increases the risk of all-cause death. It is a major risk factor for various cardiovascular and metabolic diseases. METHODS: We conducted this review through searching the related literature plus internet links. RESULTS: Recently, many researchers have been applying various efficient alternative exercise paradigms for treating obesity, such as high-intensity interval training, whole-body vibration training, and hypoxic therapy. Compared with moderate-intensity continuous training, high-intensity interval training involves a shorter exercise time but higher energy expenditure and excess post-exercise oxygen consumption via a higher exercise intensity and is effective for treating obesity. Whole-body vibration training effectively reduces the rate of fat production and accumulation through passive vibration of the whole body and improving the body composition, muscle function, and cardiovascular function of the obese population. Hypoxic therapy has been reported to improve obesity and obesity-related diseases through appetite loss, reduced dietary intake, increased energy consumption, improved glycogen storage and fatty acid oxidation, angiogenesis and left ventricle remodeling, decreased mechanical load, and reduced sarcopenia progression due to aging. CONCLUSION: The new therapeutic exercise modalities, namely, high-intensity interval training, whole-body vibration training, and hypoxic therapy, are practical, useful, and effective for improving obesity and various metabolic and cardiovascular diseases induced by obesity.

l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats.

l-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of l-carnitine administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that l-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with l-carnitine administration (1250 mg·kg-1·day-1) group, and pair-fed group adjusted hindlimb suspension. l-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition, l-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that l-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that l-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that l-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.

Nutrition Supplements to Stimulate Lipolysis: A Review in Relation to Endurance Exercise Capacity.

Athletes make great efforts to increase their endurance capacity in many ways. Using nutrition supplements for stimulating lipolysis is one such strategy to improve endurance performance. These supplements contain certain ingredients that affect fat metabolism; furthermore, in combination with endurance training, they tend to have additive effects. A large body of scientific evidence shows that nutrition supplements increase fat metabolism; however, the usefulness of lipolytic supplements as ergogenic functional foods remains controversial. The present review will describe the effectiveness of lipolytic supplements in fat metabolism and as an ergogenic aid for increasing endurance exercise capacity. There are a number of lipolytic supplements available on the market, but this review focuses on natural ingredients such as caffeine, green tea extract, L-carnitine, Garcinia cambogia (hydroxycitric acid), capsaicin, ginseng, taurine, silk peptides and octacosanol, all of which have shown scientific evidence of enhancing fat metabolism associated with improving endurance performance. We excluded some other supplements owing to lack of data on fat metabolism or endurance capacity. Based on the data in this review, we suggest that a caffeine and green tea extract improves endurance performance and enhances fat oxidation. Regarding other supplements, the data on their practical implications needs to be gathered, especially for athletes.

Gintonin enhances performance of mice in rotarod test: Involvement of lysophosphatidic acid receptors and catecholamine release.

Ginseng has a long history of use as a tonic for restoration of vigor. One example of ginseng-derived tonic effect is that it can improve physical stamina under conditions of stress. However, the active ingredient and the underlying molecular mechanism responsible for the ergogenic effect are unknown. Recent studies show that ginseng contains a novel ingredient, gintonin, which consists of a unique class of herbal-medicine lysophosphatidic acids (LPAs). Gintonin activates G protein-coupled LPA receptors to produce a transient [Ca(2+)]i signal, which is coupled to diverse intra- and inter-cellular signal transduction pathways that stimulate hormone or neurotransmitter release. However, relatively little is known about how gintonin-mediated cellular modulation is linked to physical endurance. In the present study, systemic administration of gintonin, but not ginsenosides, in fasted mice increased blood glucose concentrations in a dose-dependent manner. Gintonin treatment elevated blood glucose to a maximum level after 30min. This elevation in blood glucose level could be abrogated by the LPA1/3 receptor antagonist, Ki16425, or the ß-adrenergic receptor antagonist, propranolol. Furthermore, gintonin-dependent enhanced performance of fasted mice in rotarod test was likewise abrogated by Ki16425. Gintonin also elevated plasma epinephrine and norepinephrine concentrations. The present study shows that gintonin mediates catecholamine release through activation of the LPA receptor and that activation of the ß-adrenergic receptor is coupled to liver glycogenolysis, thereby increasing the supply of glucose and enhancing performance in the rotarod test. Thus, gintonin acts via the LPA-catecholamine-glycogenolysis axis, representing a candidate mechanism that can explain how ginseng treatment enhances physical stamina.

Protective effect of branched chain amino acids on hindlimb suspension-induced muscle atrophy in growing rats.

PURPOSE: The effect of BCAA (branched chain amino acid) administration on muscle atrophy during growth phases is not well known. We investigated whether BCAA administration can prevent the muscle atrophy induced by hindlimb suspension in growing male rats. METHODS: Male Wistar rats were assigned to 1 of 2 groups (n = 7/group): hindlimb suspension and hindlimb suspension with oral BCAA administration (600 mg·kg(-1)·day(-1), valine 1: leucine 2: isoleucine 1). After 14 days of hindlimb suspension, the weight and mRNA levels of the soleus muscle were measured. RESULTS: BCAA administration prevented a decrease in soleus muscle weight. BCAA administration attenuated atrogin-1 and MuRF1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. CONCLUSION: BCAA could serve as an effective supplement for the prevention or treatment of muscle atrophy, especially atrophy caused by weightlessness.

Red ginseng treatment for two weeks promotes fat metabolism during exercise in mice.

PURPOSE: Red ginseng (RG) has been reported to improve the blood and organ lipid profile when combined with exercise. However, the effect of RG on energy metabolism during exercise is poorly understood. Therefore, this study was designed to investigate whether RG treatment alters fat utilization during exercise; METHODS: We used seven-week-old ICR mice (n = 42). RG (1 g/kg) was administered orally daily during two weeks of endurance training. All mice were randomized into two groups: training only group (CON group) and training with RG group (RG group). Endurance training consisted of 20~25 m/min on a slope of 8° for one hour five times a week. After a two-week experimental period, we measured substrate utilization during exercise at the same intensity and duration of training using a respiratory calorimetry chamber. Mice were dissected for glycogen measurement of muscles and liver before, immediately after, and one hour after the exercise; RESULT: Fat oxidation during the initial 20 min of the one-hour exercise significantly increased in the RG group compared to the CON group. In addition, the liver glycogen stores significantly decreased immediately after the one-hour exercise compared to at rest in the RG group, but did not differ between immediately after the one-hour exercise and at rest in the RG group. The glycogen concentration in white and red gastrocnemius muscle did not differ between the groups immediately after the one-hour exercise; CONCLUSIONS: These results suggest that RG treatment for two weeks promotes fat oxidation and a glycogen-sparing effect during exercise. This might lead to a delay in peripheral fatigue during endurance exercise performance.

Silk peptide intake increases fat oxidation at rest in exercised mice.

Silk peptides (SP) have been reported to decrease body weight and accumulate fat. We investigated the effects of SP administration by using an open circuit calorimetry system on resting energy expenditure and substrate utilization in resting mice for the duration of 24 h. Seven-week-old male ICR-mice were orally administered SP (800 mg/kg) for 2 wk and were subjected to endurance training. The results indicated that not only was oxygen uptake higher in the SP group than in the CON group (*p<0.05), but also the respiratory exchange rate was lower than that in the CON group for the duration of 24 h (**p<0.01). Moreover, fat oxidation was increased in the SP group. Body weight of the SP group was significantly decreased compared to that of the CON group (*p<0.05). These results suggest that intake of silk peptides increases fat oxidation during rest in exercised mice. Intake of silk peptides is considered to be a favorable supplement for athletes in training. In particular, it would be an effective supplement for athletes who require weight loss along with an increase in muscle mass.

(-)-Hydroxycitrate ingestion and endurance exercise performance.

We have been interested in the ergogenic aid effects of food components and supplements for enhancing endurance exercise performance. For this purpose, acute or chronic (-)-hydroxycitrate (HCA) ingestion might be effective because it promotes utilization of fatty acid as an energy source. HCA is a competitive inhibitor of the enzyme ATP: citrate lyase, thereby increasing inhibition of lipogenesis in the body. Many researchers have reported that less body fat accumulation and sustained satiety cause less food intake. After focusing on exercise performance with HCA ingestion, we came up with different results that show positive effects or not. However, our previously reported data showed increased use of fatty acids during moderate intensity exercise. For future research, HCA and co-ingestion of other supplements, such as carnitine or caffeine, might have greater effect on glycogen-sparing than HCA alone.