Beneficial effects on obesity and dysmetabolism of a variety of functional ingredients contained in brown rice have attracted academic as well as clinical attention. On the other hand, it is noteworthy that the absorption efficiency of some of the functional ingredients derived from brown rice from the digestive tract is significantly low. Based on these backgrounds, we developed the “nanoparticulated brown rice germ extract” by encapsulating brown rice germ extract containing γ-oryzanol, one of the functional ingredients abundantly and specifically in brown rice (rice bran), in nanoparticles, and conducted safety and efficacy tests in humans. The present study was performed appropriately after the approval from the ethics committee of Hokkaido Information University. Japanese men and women whose BMI is 23 kg/m² or more and less than 25 kg/m², or 25 kg/m² or more and less than 30 kg/m², and whose visceral fat area is less than 100 cm² when measured by bioelectric-impedance methods were recruited for the study. We conducted a placebo-controlled, randomized, double-blind, parallel-group comparative study targeting approximately 78 people who met the eligible criteria, and examined metabolic improvements when the “nanoparticulated brown rice germ extract” tablets were ingested once-a-day continuously for 12 weeks. Although a decreasing trend was observed in the abdominal visceral fat area, which is a primary endpoint, there were no significant differences among the ingestion groups of test food (low dose group: 5 mg, and medium-dose group: 10 mg). Among the secondary endpoints, plasma LDL-cholesterol (LDL-C) level showed a marginally significant decrease in the medium and low dose (5 mg) groups compared to the control group (placebo ingestion) after 8 weeks of ingestion (p = 0.078, p = 0.098). The plasma lipid ratio (LDL-C/HDL-C) showed a significant decrease in the low dose group compared to the control group after 4 and 8 weeks of ingestion (p = 0.016, p = 0.018). The plasma non-HDL-C level showed a marginally significant or significant decrease in the medium and low dose groups compared to the control group after 8 weeks of ingestion (p = 0.099, p = 0.031). Blood level of HbA1c also showed a significant decrease in the medium-dose group compared to the control group after 4, 8, and 12 weeks of ingestion (p = 0.029, p = 0.011, p = 0.011). Furthermore, plasma level of adiponectin, which has potent anti-atherosclerotic actions, showed a marked increase in the high, medium, and low dose groups (p = 0.012, p = 0.039, p = 0.017) after 4 weeks of ingestion compared to the control group, and also showed a marginally significant or significant increase after 8 and 12 weeks of ingestion. During the hospital visit, problematic changes were not observed in blood pressure, pulse rate, general blood tests, liver and kidney functions, and urinalysis, and adverse events suggesting a causal relationship with the test food were not observed. This clinical intervention study confirmed the safety of ingestion of the “nanoparticulated brown rice germ extract”, which was also proven to improve the atherogenic lipid profile, reduce HbA1c level, and increase plasma adiponectin concentration. Results obtained tempt us to expect that nanoparticulated brown rice germ extract is well eligible for practical use.

抄録全体を表示

Glycative stress causes post-translational modifications of protein at the molecular level and increases the risks of various aging-related diseases, such as diabetic complications. There are two representative processes of the unphysiological protein modifications, i.e. (1) the carbonylation caused by aldehyde derived from glucose and lipids and the formation of advanced glycation end products (AGEs), and (2) cysteine succination derived from a disorder of the TCA cycle. Endoplasmic reticulum (ER) stress increases in pancreatic β-cells due to the formation of AGEs caused by glycative stress, and causes a reduction in insulin secretion. Lysine and arginine in amino acid sequence of insulin are susceptible to carbonyl modification and are resistant against the enzyme reaction to insulin from proinsulin. As a result, insulin synthetic quantity decreases. Approximately 9% of insulin in serum of patients with diabetes becomes glycated insulin, and it causes the patient’s insulin resistance. These findings show that glycative stress is involved not only in diabetic complications, but also the onset and development of diabetes. It has also become clear that there is a “vicious cycle” to increase the onset of diseases caused by glycative stress. Similarly, “vicious cycles” also exist through visceral fat, kidney and skeletal muscles. Recently the diseases caused by glycative stress are increasing worldwide. In order to prevent the onset and development of these diseases related to glycative stress, it is important to (1) implement countermeasures against glycative stress at an early stage and (2) understand the mechanisms of these vicious cycles and prevent them.

抄録全体を表示

Glycative stress is a comprehensive concept meaning biological stress caused by the formation and accumulation of advanced glycation end products (AGEs). The increase of glycative stress leads to the risk of onset and development of aging, diabetic complications, Alzheimer’s, and arteriosclerosis. The countermeasures against glycative stress are called anti-glycation, which includes inhibitions of postprandial hyperglycemia and glycation, the decrease of AGEs, and the lowering of dietary-derived AGEs. Oxidized protein hydrolase (OPH) is a kind of protease which is the decrease of aged protein and AGEs and is broadly distributed within living tissues. In this research, for the purpose of investigating components which decrease glycative stress, the effect of herb tea extracts on OPH activity were verified. The extracts of 58 products (38 categories) of herbal teas on OPH activity and OPH activity enhancing action was recognized in 47 herbal tea products (81%). OPH activity was observed in 34 categories (89%) of herbal tea. On the other hand, the extracts of 12 products inhibited OPH activity. Green tea (unfermented tea) and black tea (fermented tea) derived from Camellia sinesis showed an inhibitory effect; however, houji tea (roasted green tea) and pu-er tea (late fermented tea) enhanced the activity. The comparison of utilized portions of herbal teas in which an OPH activity enhancing action was observed showed that seed tea had a stronger influence than leaf tea. The active components enhancing OPH activity are possibly included in various plants. It was found that the roasting and fermenting process for tea leaves have an influence on OPH activity. It is possible that herbal teas could prevent the accumulation of aged protein and AGEs by enhancing OPH activity, and as a result, contribute to the prevention of the progression of aging caused by glycative stress.

抄録全体を表示

Objective: We investigated the effects of the intake of ostrich meat (OM), which is characterized by high protein and low fat, on the body, focusing on protein and amino acid metabolism and growth hormone (GH) secretion. Methods: Plasma amino acid levels, growth hormone (GH) secretion after exercise and autonomic nervous function (device used: VM500 [Fatigue Science Laboratory Inc.]) were measured in 12 healthy subjects (33.3 ± 6.9 years old, BMI 21.6 ± 1.6) after ingestion of the test food (OM) or control food for one week each. Results: A significant increase in the blood levels of branched-chain amino acids (BCAAs), lysine and histidine, and an increase in those for 1-methylhistidine and 3-methylhistidine, which are the indicators of muscle protein breakdown, were observed after the intake of OM, suggesting that protein metabolism in the muscles was activated. Subclass analysis excluding cases with high GH before exercise load showed a significant increase in GH secretion after a walking exercise (30 min) only after the intake of OM. The autonomic nervous function test did not reveal any significant findings. There were no OM-related adverse events during the study. Conclusion: OM is a low-fat meat containing physiologically significant amino acids in large quantities, and it was suggested that OM could be safe and suitable for a protein and amino acid supplement.

抄録全体を表示

An adrenal-derived androgen, dehydroepiandrosterone (DHEA), gradually reduces along with aging. It has been suggested that DHEA is an effective index for aging and has relationships with geriatric syndromes. There are suggestions that the decreased DHEA is related to the onset and progression of metabolic syndrome and diabetes mellitus and the decrease of bone mineral density, in terms of diseases. However, the underlying mechanisms are unknown to a great extent. Focusing on the relationship with diabetes mellitus, a large number of studies on animal models and cells, and cross-sectional studies on humans have suggested that DHEA has anti-diabetic properties. Nevertheless, longitudinal studies on humans and studies on DHEA administration with a small number of subjects have not led to a valid conclusion, providing controversial outcomes. Type II diabetes mellitus is known to exacerbate oxidative stress. The increase of reactive oxygen species in the blood, the decline of defense systems against oxidative stress, and the accumulation of glycation products are observed. Interestingly, it is indicated that DHEA administration to patients with type 2 diabetes improves these phenomena. Inhibitory effects of DHEA on arteriosclerosis are suggested and there is a potential that the effects are exerted along with the above effects against diabetes. DHEA has a variety of favorable properties for hormone replacement therapies in anti-aging fields. Further progress is expected for research on DHEA.

抄録全体を表示

The true nature of illness is interpreted by the theories of Yin-Yang Five Elements, meridians, acupuncture points, vital energy and blood and 5 viscera and 6 bowels of “Huangdi Neijing ” in China. There are 12 main meridians and 8 extra meridians. The main meridians are classified into yin and yang meridians. A yin meridian is divided into three, greater yin, lesser yin and faint yin, and yang is also divided into three, greater yang, yang bright and lesser yang. The 12 main meridians belong to the three yang and three yin meridians in each of the hands and feet. In Chinese medicine, the trueness of the body is determined by measuring the 12 main meridians. In the thermal sensitivity measurement method, diagnosis is performed by applying a thermal stimulus to the body surface of subjects corresponding to the meridians. In this paper, we are reporting the development of a meridian thermal stimulation diagnostic device that assists in the measurement and analysis using the thermal sensitivity measurement method. This method was used to measure the heat sensitivity in 31 Japanese subjects (13 males, 18 females, 65 to 90 years old), and 200 Chinese subjects (62 males, 138 females), and the association between glycative stress index and Skin AGEs Fluorescence (SAF) was analyzed. As a result, The Bladder Meridian of Foot-Taiyang and The Kidney Meridian of Foot-Shaoyin were found to have a significant association with SAF. When the measured values for bladder meridian and kidney meridian were within the standard range, SAF tended to be low. We plan to verify whether it is possible to predict the risk of disease in the pre-symptomatic stage by collecting measurement data on thermal sensitivity.

抄録全体を表示

Lifestyle and dietary habits aimed at the reduction of glycative stress are called anti-glycation. Specific measures for anti-glycation include reduction of postprandial glucose elevation, inhibition of glycative reaction, decomposition and excretion of advanced glycation end products (AGEs) produced and reducing the intake of AGEs in the diet. Since food contains nutrients such as proteins, lipids and carbohydrates, glycation proceeds during cooking, processing and storage. Melanoidins are dark brown substances in food having physiological functions such as imparting brown color to food and having an anti-oxidant effect (so-called “good AGEs”). On the other hand, heterocyclic amine, and acrylamide in food are substances that are involved in mutagenicity and carcinogenicity (so-called “bad AGEs”). Most AGEs ingested from food, are excreted in the urine. However, it is reported that AGEs contained in ingested food may accumulate in the body of patients with chronic renal failure caused by impaired renal function. In healthy persons, about 7% of the AGEs contained in ingested food may remain in the body. To suppress the effects of AGEs in food on the body, we can consider selecting a cooking method that produces fewer AGEs and the reduction of AGEs absorption in the body. Although various analytical methods have been reported for measuring AGEs in food, there are few examples where pretreatment methods of samples have been studied in detail. It is necessary to verify the effects of ingested AGEs in food, the accuracy of AGEs measurement, health condition, and eating habits of the person ingesting the food.

抄録全体を表示

Purpose: Results of previous studies suggest that improved sleep quality improves the secretion of growth hormone/insulin-like growth factor-I (IGF-I) and melatonin. In this study, we verified the effects of a mattress with “A Distinctive 4-Layer 3D Structure” as the study product, on sleep quality, skin quality, and fatigue, through a non-controlled open-label study. Method: 12 women (age 50.1 ± 4.9 years) with strong subjective and objective findings were selected from among 33 women who were dissatisfied with sleep and skin quality. A non-controlled open-label study was conducted for changes in physical information when the study product was used for 8 weeks. The study product was provided by Nishikawa Co., Ltd. (Chuo-ku, Tokyo). Pittsburgh Sleep Quality Index (PSQI-J), Anti-Aging QOL Common Questionnaire (AAQol), verification of subjective symptoms using Visual Analogue Scale (VAS), anthropometric measurements, skin moisture, transepidermal water loss (TEWL), skin viscoelasticity, and blood biochemistry tests were conducted before the commencement of the study and at 4 and 8 weeks after the start of the study. This study was conducted with the approval of the ethics review committee. Results: PSQI-J showed a significant improvement in sleep quality, time to fall asleep, difficulty sleeping, and daytime difficulty waking, 8 weeks after the start of the study. The PSQI global score improved significantly from 8.2 ± 1.4 to 4.2 ± 2.2 (p < 0.01). AAQoL and VAS also showed a significant improvement in symptoms related to sleep and fatigue. For skin quality (upper arm), the skin moisture increased significantly after 8 weeks (+35.9%, p < 0.05), and reactivity of TEWL also increased (+16.9%, p < 0.01). The skin viscoelasticity index R2 increased significantly after 8 weeks (p < 0.05). Conclusion: Improvements in subjective symptoms related to sleep and fatigue and improvement in skin quality (moisture and viscoelasticity) were observed with the use of the study product, suggesting that the improvement in sleep quality may also contribute to cosmetic effects.

抄録全体を表示

This study reports outcomes of investigations of special-glaze-applied ceramic pieces and water which was treated with the ceramic pieces. The ceramic pieces were developed in 2000 and used for the purpose of environmental improvements. They were pieces of bisque fired ceramics manufactured with the application of a special glaze and were characterized by a porous structure. Investigations have confirmed diverse effects from the use of ceramic pieces such as water purification, bactericidal action and soil amelioration, although the mechanisms have not been identified. However, it has been clarified currently that cyanobacteria are proliferated in the ceramic periphery. Cyanobacteria produce oxygen via the fixation of nitrogen and carbon, which exist in water and soil. Cases with the use of ceramic pieces and the treated water indicated the effectiveness of odor decomposition, bactericidal activities, and the water quality improvement due to the reduction of biochemical oxygen demand (SOD). A theory could explain the mechanisms of these effects; that cyanobacteria of the ceramic enhances oxidation due to its oxygen production and induces these effects. Improvements of carbohydrate metabolism due to ceramic pieces were confirmed in C57BLKS/J Iar -＋Lepr^db /+Lepr^db, type 2 diabetes animal models , with the ingestion of ceramic-treated water. Mechanisms for this finding have not been identified. Soil improvement effects were observed for the salt pollution caused by the tsunami of the Great East Japan earthquake in 2011 and the radioactive contamination following the Fukushima Nuclear Power Station accident. The ceramic pieces have diverse effects and further influences can exert global-scale significance for environmental improvements and increased agricultural productivities.

抄録全体を表示

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone secreted from the pineal gland during the night and is known as a synchronizer of the circadian rhythm. It is a hormone that has been present not only in vertebrates but all kinds of living organisms. Recently, several reports showed that the hormone plays very important roles such as energy metabolism and glucose metabolism, in particular. It has been reported that in animal models of type 2 diabetes, melatonin ameliorates glucose homeostasis by improving insulin action in muscles and adipose tissues. We demonstrated that melatonin treatment increased glucose uptake in a dose-dependent manner in a primary culture of goldfish brain cells using insulin-free medium. These findings suggest that nocturnal melatonin increases glucose uptake in the brain via insulin independent action. To the best of our knowledge, this study is the first to demonstrate that nocturnal melatonin directly regulates glucose uptake in place of insulin in a vertebrate species. In this paper, we introduce new findings concerning glucose metabolism by melatonin on mammals, and consider a role of melatonin in aspect of the evolution of glucose metabolism.

抄録全体を表示