Miki Tokunaga

Effect of Brain Derived Neurotrophic Factor, In Relation to Diet and Lifestyle Factors, for Prevention of Neuropsychiatric and Vascular Diseases and Diabetes

Background: Brain-derived neurotrophic factor (BDNF) is a major neurotrophin which may have promise to be a nutraceutical of this decade. It has a documented role in neurogenesis, angiogenesis, and neuronal survival. BDNF can have beneficial effects on several cardio-metabolic and neuro-psychiatric disorders, indicating that it is important in brain- body interactions. Diet and lifestyle factors may also have an influence on BDNF levels. In this review, we examine the beneficial role of BDNF on risk factors of vascular diseases, type 2 diabetes mellitus and anxiety disorders. Methods: In- ternet search and discussion with peer colleagues. Results: Majority of the BDNF (70-80%) is derived from dendrite of neurons but it is also present in other body tissues. BDNF controls the food intake and appetite as well as lipid and glu- cose metabolism. Sedentary behavior and tobacco intake may be associated with BDNF deficiency. Lower serum concen- tration of BDNF and higher vascular endothelial growth factor (VEGF) concentrations were associated with increased risk of incident stroke/TIA. BDNF may serve as an intermediate biomarker for subclinical vascular disease and may also have biological potential to serve as a therapeutic target for primary and secondary prevention of vascular diseases, as well as clinical and subclinical vascular brain disease. BDNF deficiency has been observed in association with anxiety, depres- sion, insomnia, dementia, insulin resistance, type 2 diabetes and vascular diseases. The phenotypes associated with insulin resistance are at increased risk for developing cognitive decline and neuro-degeneration resulting in vascular dementia, and depression as well as diabetes mellitus and metabolic syndrome, which are risk factors for CVDs. BDNF may be ad- ministered as nutraceutical due to its protective influence on BDNF concentrations, insulin receptors and hypothalamic dysfunction leading to beneficial effects on cardiovascular risk and neuropsychological dysfunction. It is proposed that omega-3 fatty acids and moderate physical activity may enhance BDNF release. Conclusions: It is possible that circulat- ing BDNF deficiency is a risk factor for obesity, CVDs and diabetes as well as risk factor for neuropsychiatric diseases. BDNF administration may modify the risk of clinical and subclinical stroke, depression, and dementia as well as of obe- sity and type 2 diabetes.

Study of Functional Foods Consumption Patterns Among Decedents Dying Due to Various Causes of Death

Background: Western diet appears to be a risk factor for non-communicable diseases (NCDs), cardiovascular diseases (CVDs), diabetes and cancer whereas dietary supplements of functional foods rich Mediterranean diets are inversely associated, among individuals and populations with underlying lack of general and health education. We have only scanty information about functional foods which may be considered as nutraceuticals. The prevalence of optimal functional food eating behavior pattern in the population is unknown. This study examines the prevalence of optimal functional foods eating behavior as a protective factor among victims dying due to NCDs to find out the accuracy of the verbal autopsy questionnaire. Subjects and Methods: Death records of 2,222 (1,385 men and 837 women) decedents, aged 25-64 years, out of 3,034 death records, were randomly selected and studied by verbal autopsy questionnaires. All the risk factors and protective factors were assessed by questionnaires which were completed with the help of the victims spouse and a local treating doctor, by a trained scientist. The lack of knowledge on health education about the role of adverse effects of Western foods was assessed by the questionnaires. Functional food intake was considered in presence of fruit, vegetable and legume intake of minimum 250g/day (moderate) and ideally 400g/day consistent with WHO guidelines. Results: The prevalence of optimal prudent foods intake behavior; fruit, vegetable and legume (>250g/day) intake were observed among 51.4% (n=712) men and 50.4% (n=422) women. Western type food (>255g/day)intake was observed among 63.2% (n=875)men and 59.9% (n=502) women. The prevalence of optimal functional food intake was significantly greater among men compared to women (19.4 vs 14.6%, P<0.05). The consumption of functional food not fruits; grapes and apples, guava, stargoose berry and lemon and onion, garlic ginger was significantly greater among men as compared to women. Other functional foods such as soy products, mustard or olive oil, curd or yogurt, nuts and fish, tea and cocoa, spices; turmeric, cumin, coriander seeds and peppers intake showed no significant difference between two sexes. Multivariate logistic regression analysis revealed that after adjustment of age and body weight, total functional foods intakes and fruit, vegetable, legume and nuts intake were significantly inversely associated with deaths due to NCDs, whereas Western type foods (red meat and eggs, refined foods ) were positively associated with these causes of deaths, in both sexes. Total spices intake, mustard/olive oil intake and curd or yogurt intake, were inversely but weakly associated with causes of deaths due to NCDs, among both men and women. The prevalence of protective behavior pattern was observed among half of the victims, dying due to injury and accidents where such behaviors were uncommon among decedents dying due to NCDs. Conclusions: It is possible that protective health behavior about functional food intake can be accurately assessed by a verbal autopsy questionnaire administered to a spouse of the decedents among Indians. The consumption of functional food appears to be lower among victims dying due to CVDs and cancer.

Reversal of Immunogenicity of Hepatitis B Antigen by Treatment with Nutraceuticals (OMEGA QGEL)

Two patients presented with positive hepatitis B virus antigen reactivity. Both the patients had medical records indicating clinical and biochemical manifestations of viral hepatitis. Treatment with coenzyme Q10 and w-3 fatty acids was associated with reversal of antigenicity causing negative hepatitis B antigen reactivity.

Increased Subjective Distaste and Altered Insula Activity to Umami Tastant in Patients with Bulimia Nervosa

The aim of this study was to examine differences in brain neural activation in response to monosodium glutamate (MSG), the representative component of umami, between patients with bulimia nervosa (BN) and healthy women (HW) controls. We analyzed brain activity after ingestion of an MSG solution using functional magnetic resonance imaging (fMRI) in a group of women with BN (n = 18) and a group of HW participants (n = 18). Both groups also provided a subjective assessment of the MSG solution via a numerical rating scale. The BN group subjectively rated the MSG solution lower in pleasantness and liking than the control group, although no difference in subjective intensity was noted. The fMRI results demonstrated greater activation of the right insula in the BN group versus the control group. Compared with the HW controls, the BN patients demonstrated both altered taste perception-related brain activity and more negative hedonic scores in response to MSG stimuli. Different hedonic evaluation, expressed as the relative low pleasing taste of umami tastant and associated with altered insula function, may explain disturbed eating behaviors, including the imbalance in food choices, in BN patients.

Effect of Diet and Nutrient on Cell Signaling: Is the Tissue the Main Issue,Proposes Dr. Wilson?

Western diet is characterized with energy dense, refined, ready prepared foods with a high glycemic index (e.g. refined starches; bread, biscuits, candies, cornflakes, pizza, potato chips, cola drinks and sugar) and unhealthy lipids (e.g. trans fats, saturated fat , w-6 rich oils) poor in w-3 fatty acids, phytochemicals and fiber that are abundant in the Mediter- ranean type of diet. Western type of diets are known to predispose inflammation and increase in free fatty acids causing endothelial cell and beta cell dysfunction leading to the epidemic of cardiovascular diseases (CVDs). The cell signaling and the changes in cell membrane properties of the tissues induced by dietary lipids may have important consequences on the development of obesity, atherosclerosis and hypertension. The structural properties and function of cell membrane proteins appear to be modified in hypertensive humans and animal models of hypertension and atherosclerosis. Diet in- duced alterations in membrane lipid composition of hypertensive subjects have been associated with alterations in the transmembrane fluxes of Na + and K + , including Na + -Li + countertransport, which is a marker of essential hypertension, and in cell signaling proteins that participate in the control of blood pressure. It has been demonstrated that dietary lipids have an effect on membrane lipid composition and cell signaling proteins. Since changes in the dietary lipid composition yield to variations in the biophysical properties of the plasma membrane, it is likely that cellular functional changes could result from alterations in the structure of the lipid membrane properties under influence of the diet. Thus, the changes in mem- brane properties induced by dietary lipids may have important consequences on blood pressure regulation. The Mediterra- nean diet has been associated with changes in membrane structure and function. Consumption of olive oil-rich diets in- creases the concentration of oleic acid in plasma membrane lipids of different rat and human cells, with beneficial conse- quences on membrane functionality. In contrast, very little is currently known regarding the effects of nuts, another key ingredient of such diets, on membrane lipid composition and structure. CVD, diabetes mellitus and obesity, that are asso- ciated with increased production of thromboxane A2(TXA2), leukotrienes, prostacyclin, interleukins-1 and 6, tumor ne- crosis factor-alpha and C-reactive proteins in the tissues, is the major issue. Increased dietary intake of w-6 fatty acids is known to enhance all these biomarkers as well as atherogenicity of cholesterol in the tissues which have adverse pro- inflammatory effects resulting in CAD. Mediterranean diet rich in fruits, vegetables, nuts, mustard oil, and olive oil char- acterized with low w-6/w-3 ratio in the diet, can modulate inflammation and endothelial dysfunction of the tissues and may be protective against risk of coronary artery disease (CAD) and all-cause mortality. Inflammation appears to be an important unifying hypothesis, because in the absence of inflammation in the tissues, total cholesterol and other lipids may have neutral effects in the arterial tissues and myocardium. Therefore, it seems that endothelial dysfunction and in- flammation in the tissue is the main issue for treatment.

Association of Wealth and Mortality Due to Cardiovascular Diseases Thank You. Dr. Wilson

Industrialization and urbanization may be associated with increase in income, resulting in increased consump- tion of ready-prepared Western foods, meat and eggs and cola drinks and decreased intake of traditional foods; whole grains, and vegetables. There is also associated greater use of automobiles causing sedentary behaviours, due to decreased occupational physical activity. These diet and lifestyle factors predispose obesity and central obesity which is a risk factor of cardiovascular diseases (CVDs) mortality.

Association of Western Diet and Lifestyle with Circadian Hyperamplitude Tension and Mesor Hypertension Measured by Ambulatory Blood Pressure Monitoring

Effects of Western diet and lifestyle factors resulting in hypertension are known, however, the effects of life- style on blood pressure variability measured by ambulatory blood pressure monitoring are not sufficiently well known. In the present case, it has been observed that Western diet, sedentary behavior and mental load in a subject with normal blood pressures were associated with blood pressure disorders (VVD). Moderation in diet and lifestyle reversed the blood pressure variability, demonstrated by ambulatory blood pressure monitoring.

New Developments in Coenzyme Q10 Research Contributed by A Single Group. Editorial

Coenzyme Q10 (CoQ10), first identified by Moor et al in 1940, is a fat soluble quinone with characteristics common to vitamins [1]. It is found in the organs of various animal species with highest concentrations in the heart, liver, kidney, muscles and pancreas [2, 3]. Festenstein et al in 1955 named the substance ubiquinone [2] while Crane et al in 1957 choose the name coenzyme Q [4]. Ubiquinone is a component of the mitochondrial respiratory chain, participating in electron transport in NADH-coenzyme Q reductase (complex I), succinate coenzyme Q reductase (complex II) and the cytochrome system [4, 5]. Folkers and his group determined the structure of the quinone moiety which was found identical to that described by Morton and his team, and suggested the name “ubiquinone” referring to the ubiquitous occurrence of this compound in various tissues [2-5]. It is also rich in pancreas and may be protective against type 2 diabetes [6]. In 1957, Crane et al demonstrated that it has an important role as a redox carrier in the mammalian respiratory transport chain [4]. A high concentration of CoQ10 observed in healthy human myocardium has led to the assumption that a myocardial deficiency of CoQ10 is detrimental to cardiac function [7]. In 1972, Littarru, of Italy and the late Prof. Folkers from Texas, documented a deficiency of CoQ10 in human heart disease, particularly among patients subjected to bypass surgery in Houston, USA [8-10]. Lower than normal levels of CoQ10 have also been found in blood samples from patients with cardiovascular diseases (CVDs) compared with levels in healthy human subjects [9, 10]. Yamamura and his group were the first to use CoQ10 for the treatment of cardiovascular disease (CVD) in the 1960’s [11] and later Folkers et al. presented the rationale for using CoQ10 in treating congestive heart failure (CHF) [8].