Necessity of daily 1000-IU vitamin D supplementation for maintaining a sufficient vitamin D status.

The changes in the serum 25-hydroxyvitamin D (25(OH)D) concentrations after daily 1000-IU vitamin D intake for 3 months (3-month-VD), 6 months (6-month-VD) and then 6-month cessation of vitamin D in-take (6-month-VD cessation) were examined. The serum 25(OH)D levels in 11 male and 16 female subjects were 12.1±3.5 ng/mL at baseline, increased to 27.1±4.7 ng/mL at 3-month-VD, 28.5±5.1 ng/mL at 6-month-VD and decreased to 16.4±4.0 ng/mL at 6-month-VD cessation. The present study suggested that a vitamin D intake of 1000 IU/day is required to maintain the 25(OH) D concentration at 30 ng/mL or higher without vitamin D intoxication. J. Med. Invest. 69 : 135-140, February, 2022.

Effects of daily 1,000-IU vitamin D-fortified milk intake on skeletal muscle mass, power, physical function and nutrition status in Japanese.

An intervention study was conducted to investigate the effects of daily 1,000-IU vitamin D-fortified milk intake on skeletal muscle mass, power, physical function and nutrition status in 26 healthy people and 8 older adults living in a nursing home. The serum 25-hydroxyvitamin D [25(OH)D] level was 13.4 ±â€…0.8 ng / mL and it markedly increased to 29.6 ±â€…0.9 ng / mL after daily 1000-IU vitamin D-fortified milk intake for 6 months. Handgrip strength (kg) also significantly increased in the 21-50 years and total groups, and male subjects, and the timed up and go test significantly improved in the 21-50 years and total groups, and female subjects after 6-month vitamin D intake. However, there were no significant differences between baseline and post-treatment in the Barthel Index (BI), walking speed (m / sec) or skeletal muscle mass (kg, % of BW, kg / m2). Therefore, the present study suggested that vitamin D-fortified milk intake is effective at improving muscle strength and physical function in Japanese, although further studies are needed, particularly for older adults. J. Med. Invest. 68 : 249-255, August, 2021.

Dietary phosphate supplementation delays the onset of iron deficiency anemia and affects iron status in rats.

Inorganic phosphate (Pi) plays critical roles in bone metabolism and is an essential component of 2,3-diphosphoglycerate (2,3-DPG). It has been reported that animals fed a low-iron diet modulate Pi metabolism, whereas the effect of dietary Pi on iron metabolism, particularly in iron deficiency anemia (IDA), is not fully understood. In this study, we hypothesized the presence of a link between Pi and iron metabolism and tested the hypothesis by investigating the effects of dietary Pi on iron status and IDA. Wistar rats aged 4 weeks were randomly assigned to 1 of 4 experimental dietary groups: normal iron content (Con Fe)+0.5% Pi, low-iron (Low Fe)+0.5% Pi, Con Fe+1.5% Pi, and Low Fe+1.5% Pi. Rats fed the 1.5% Pi diet for 14 days, but not for 28 days, maintained their anemia state and plasma erythropoietin concentrations within the reference range, even under conditions of low iron. In addition, plasma concentrations of 2,3-DPG were significantly increased by the 1.5% Pi diets and were positively correlated with plasma Pi concentration (r=0.779; P<.001). Dietary Pi regulated the messenger RNA expression of iron-regulated genes, including divalent metal transporter 1, duodenal cytochrome B, and hepcidin. Furthermore, iron concentration in liver tissues was increased by the 1.5% Pi in Con Fe diet. These results suggest that dietary Pi supplementation delays the onset of IDA and increases plasma 2,3-DPG concentration, followed by modulation of the expression of iron-regulated genes.

Excessive dietary phosphorus intake impairs endothelial function in young healthy men: a time- and dose-dependent study.

Excessive dietary phosphorus (P) has been speculated to be a risk factor for cardiovascular disease (CVD). Here, we performed a double-blinded crossover study to investigate the time- and dose-dependent effects of dietary P intake on endothelial function in healthy subjects. Sixteen healthy male volunteers were given meals containing 400, 800, and 1,200 mg P (P400, P800, and P1200 meals, respectively) with at least 7 days between doses. There were no differences in nutritional composition among the experimental diets except for P content. Blood biochemistry data and flow-mediated dilation (%FMD) of the brachial artery were measured while fasted, at 0 h, 1 h, 2 h, and 4 h after meal ingestion, and the next morning while fasted. The P800 and P1200 meals significantly increased serum P levels at 1-4 h after ingestion. A significant decrease in %FMD was observed between 1-4 h,while the P400 meal did not affect %FMD. We observed no differences among meals in serum P levels or %FMD the next morning. A significant negative correlation was observed between %FMD and serum P. These results indicate that excessive dietary P intake can acutely impair endothelial function in healthy people.

Flaxseed oil intake reduces serum small dense low-density lipoprotein concentrations in Japanese men: a randomized, double blind, crossover study.

BACKGROUND: The effects of alpha-linolenic acid (ALA) on cardiovascular risk factors considerably vary between published reports. Therefore, we investigated the effects of 12-week supplementation with flaxseed oil (FO), which is a rich source of ALA, on cardiovascular risk factors such as serum small dense low-density lipoprotein (sd-LDL) concentrations. METHODS: In a randomized, double blind, crossover study, 15 subjects ingested 10 g of FO or corn oil (CO), containing 5.49 g and 0.09 g of ALA, respectively, once daily with dinner. Blood samples were collected at 0, 4 and 12 weeks, and were used for analysis of serum lipid, lipid-related proteins, serum fatty acids and serum sd-LDL cholesterol. Differences during the test period were identified using a repeated-measures analysis of variance (ANOVA) for within-group effects. Group differences were identified using paired t-test at each blood sampling time point. RESULTS: ALA and eicosapentaenoic acid concentrations were significantly higher in the FO period at 4 and 12 weeks than in the CO period. No significant differences in docosahexaenoic acid concentrations were observed between two periods, and cholesteryl ester transfer protein and apolipoprotein B concentrations were significantly lower in the FO period than in the CO period at 12 weeks. FO supplementation was associated with a significant decrease in sd-LDL concentrations at 4 and 12 weeks, and CO supplementation had no effect. Moreover, sd-LDL concentrations were significantly lower in the FO period than in the CO period at 4 weeks. Among subjects with triglyceride (TG) concentrations of >100 mg/dl, FO supplementation markedly reduced sd-LDL concentrations at 4 and 12 weeks compared with baseline. Sd-LDL concentrations significantly differed between the periods at both 4 and 12 weeks. CONCLUSION: This study indicates that the FO, which is a rich source of ALA, leads to lower sd-LDL cholesterol concentrations.

Influenza virus-host interactome screen as a platform for antiviral drug development.

Host factors required for viral replication are ideal drug targets because they are less likely than viral proteins to mutate under drug-mediated selective pressure. Although genome-wide screens have identified host proteins involved in influenza virus replication, limited mechanistic understanding of how these factors affect influenza has hindered potential drug development. We conducted a systematic analysis to identify and validate host factors that associate with influenza virus proteins and affect viral replication. After identifying over 1,000 host factors that coimmunoprecipitate with specific viral proteins, we generated a network of virus-host protein interactions based on the stage of the viral life cycle affected upon host factor downregulation. Using compounds that inhibit these host factors, we validated several proteins, notably Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) and JAK1, as potential antiviral drug targets. Thus, virus-host interactome screens are powerful strategies to identify targetable host factors and guide antiviral drug development.

[Calcium pros and cons significance and risk of phosphorus supplementation. The necessity of phosphorus supplementation for hypophosphatemia].

Phosphate plays a vital role forming the high-energy band within ATP. The pathophysiological results of phosphate deficiency are inadequate supplies of energy-rich phosphates and, in particular, inhibition of glyceraldehyde-3- phosphate dehydrogenase, which occupies a key position in glycolysis. The effect of this on the central nervous system, muscle and erythrocyte energy metabolism is to reduce ATP and 2,3-diphosphoglycerate levels, leading to left-hand displacement of the oxygen-hemoglobin dissociation curve with decreased peripheral oxygen uptake and transport. Therefore, detection and treatment of acute hypophosphatemia is important in many hospitalized patients particularly in ICU patients. Severe hypophosphatemia is also associated with a number of neuromuscular and cardiovascular sequelae, in which phosphate supplementation leads to improved symptoms and clinical parameters. In clinical practice it is common on administering 0.4 mmol (12 mg) phosphate/kg per day, and to adjust this on the basis of the serum phosphate analysis.

Inhibitory effect of 1α-hydroxyvitamin D3 on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in Syrian hamsters.

Sixty-three male 5-week-old Syrian hamsters received the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) s.c. in 5 weekly injections (the first, 70 mg/kg body, and the remaining, 20mg/kg each). The hamsters that received BOP were given intragastric administration of 0.2 ml of medium chain triglyceride (MCT) with or without 0.04 µg of 1α-hydroxyvitamin D3 [1α(OH)D3] through a feeding tube for 12 weeks. Thus, 3 groups were assigned:Group 1;BOP alone (n＝20), Group 2;BOP＋MCT (n＝18) and Group 3;BOP＋1α(OH)D3 (n＝25). The mean body weight of Group 3 was lower than those of Groups 1 and 2 at the end of the experiment (p＜0.001,Tukey-Kramer HSD test). At the end of week 12, all surviving hamsters were put to sleep. The incidences of liver tumors were 80%, 72% and 32% in Groups 1, 2 and 3, respectively. The incidence of tumors in Group 3 was significantly lower than in Group 1 and Group 2 (p＜0.05, χ2-test). All tumors were cholangiocarcinoma. These results indicated that BOP-induced cholangiocarcinogenesis was suppressed by the supplemental administration of 1α(OH)D3.

Protective effects of glycoglycerolipids extracted from spinach on 5-fluorouracil induced intestinal mucosal injury.

Glycoglycerolipids are mostly found in plants, however the beneficial effects of the glycoglycerolipids on mammalian body have not been understood. In this study, we investigated the effects of glycolipid extracts from spinach, which highly contained glycoglycerolipids, on mucosal injury induced by 5-fluorouracil (5-FU) in rats. Preadministration of glycolipid extracts from spinach (20 mg/kg body weight) prevented villous atrophy, misaligned crypts, and increased inflammatory cytokines in rat jejunum treated with 5-FU (300 mg/kg body weight) compared with the extracts from soybean. The glycolipid extracts from spinach highly contained monogalactosyl-diacylglycerol (MGDG) and diglactosyl-diacylglycerol (DGDG). In Caco-2 cells, MGDG and DGDG inhibited the production of reactive oxygen species induced by phorbol ester. We concluded that glycolipid extracts from spinach has anti-oxidative and anti-inflammatory effects, and the extract may be useful for prevention of drug-induced mucosal injury and other inflammatory diseases. Tokushima

The effect of leg hyperthermia using far infrared rays in bedridden subjects with type 2 diabetes mellitus.

We examined the effect of leg hyperthermia on oxidative stress in bedridden subjects with type 2 diabetes mellitus using 15-min sessions of far infrared rays over a two-week period. Four subjects (male 1, female 3) incapacitated by a stroke were recruited for this study. All patients were admitted to Takahashi Central Hospital and ate the same hospital meals. Fasting plasma glucose, HbA1c, tumor necrosis factor (TNF)alpha, free fatty acid, leptin, adiponectin and plasma 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) levels as a marker of oxidative stress were measured on admission, just before and 2 weeks after local heating of the leg. Results showed that plasma total 8-epi-PGF2alpha levels were decreased significantly while TNFalpha levels were increased significantly. On the other hand, glucose, HbA1c, free fatty acid, leptin and adiponectin levels were not changed during the study period. These results suggest that repeated leg hyperthermia may protect against oxidative stress.

Consultation clinics for complementary and alternative medicine at Japanese university hospitals: An analysis at Tokushima University Hospital.

Here, we report on a Consultation Clinic for Complementary and Alternative Medicine (CAM) which we established at Tokushima University Hospital in July of 2007 with the aim of providing person-to-person information on CAM, though not CAM therapy itself. In December of 2008, we received 55 applications for consultation, 37% concerning health foods, 37% Japanese herbal medicine (Kampo), and 26% various other topics. The consultants (nutritionists and pharmacists) communicated individually with 38 applicants; malignancies (26%) and cardiovascular disease (24%) were the main underlying concerns. To promote the quality of consultation, data was collected by means of focus group interviews concerning the perspective of the consultants. Safe and effective use of CAM requires a network of communication linking individuals, consultation teams, physicians, primary care institutions and university hospitals. To advance this goal, we plan to broaden the efforts described herein. Our findings indicate that the specific role of the consultation clinic in promoting the scientific use of CAM merits further study.

Dietary phosphorus acutely impairs endothelial function.

Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

Fermented ginseng improves the first-night effect in humans.

STUDY OBJECTIVES: The goal of this study was to clarify whether ginseng fermented by lactic acid bacteria (fermented ginseng, FG), can improve the first-night effect (FNE) in humans. DESIGN: Behavioral tests and quantification of mRNA expression related to GABAergic neurotransmission in brain (glutamic acid decarboxylase 1, gamma-aminobutyrate aminotransferase [Abat], gamma-aminobutyric acid transporter 1 [GAT1], gamma-aminobutyric acid transporter 4, gamma-aminobutyric acid A receptor subunit alpha 1 and gamma-aminobutyric acid A receptor subunit alpha 2) were carried out in FG-treated mice. We also performed double-blind sleep recordings of human subjects given FG or placebo. SETTING: A university-based sleep laboratory. PATIENTS OR PARTICIPANTS: Sixteen healthy male volunteers (aged 20.69 +/- 0.44 years) were observed in the human study. INTERVENTIONS: At the end of administration, 2 consecutive all-night polysomnography recordings were performed. Subjects also completed psychological questionnaires, and urine and saliva samples were taken to analyze stress-sensitive markers. MEASUREMENTS AND RESULTS: The light-dark transition test demonstrated that FG had some anxiolytic effect in mice, but other anxiety measures were unaffected. The hippocampal mRNA expression showed a decrease of Abat and GAT1 suggesting an increase of GABA. Other regions (amygdala and cerebellum) showed no differences. Furthermore, there was some evidence (using simple pairwise comparisons but not supported in the full ANOVA model) that administration of FG tended to diminish decreases in total sleep time and sleep efficiency (seen as first night effects in the placebo group) without affecting sleep architecture. CONCLUSIONS: Our results suggest the administration of FG could improve the FNE in humans. The improvement may be related to an anxiolytic effect of FG which acts via GABAergic modification.

Nutritional treatment of a patient with hepatic cirrhosis with the novel low glycemic index liquid food (Inslow).

A sixty-six year-old patient with liver cirrhosis and diabetes was nutritionally treated by administration of the low glycemic index liquid food (Inslow) as a late evening sack (LES) for 6 weeks. The mean energy intake increased from 825+/-48 kcal/d to 1567+/-66 kcal/d after the 6-week treatment period. The fasting glucose level did not change, remaining at about 100 mg/dl throughout this period. Interestingly, the amount of insulin administered was reduced from 38 units before treatment to 28 units in the fifth week of treatment without a change in the fasting glucose level. This indicates a marked improvement in insulin sensitivity due to Inslow administration in this patient. In conclusion, the long-term administration of Inslow as an LES may be an effective treatment for cirrhotic patients.

Water extract of Cordyceps sinensis (WECS) inhibits the RANKL-induced osteoclast differentiation.

It has been reported that Cordyceps sinensis, a traditional Chinese medicine, has various pharmacological effects. The aim of this study was to clarify the effect of water extract of Cordyceps sinensis (WECS) on osteoclast differentiation in vitro. In mouse bone marrow cells and monocyte/macrophage cell line RAW264.7, WECS dose-dependently inhibited the receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL)-induced osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. In fact, cytotoxic effect was not observed in the RAW264.7 cells treated with WECS. Moreover, the mRNA expression of osteoclast related genes (calcitonin receptor, cathepsin K, matrix metalloprotease 9 and nuclear factor of activated T cells c1) was also inhibited by WECS. Investigation of inhibitory mechanism by using electrophoretic mobility shift assay (EMSA) and Western blot analysis revealed that WECS inhibited the activation of NF-kappaB through the prevention of IkappaBalpha phosphorylation. In conclusion, the present results demonstrate for the first time that WECS is a potent inhibitor of the RANKL-induced osteoclast differentiation through a mechanism involving the NF-kappaB pathway.

Extracts of Momordica charantia suppress postprandial hyperglycemia in rats.

Momordica charantia (bitter melon) is commonly known as vegetable insulin, but the mechanisms underlying its hypoglycemic effect remain unclear. To address this issue, the effects of bitter melon extracts on postprandial glycemic responses have been investigated in rats. An aqueous extract (AE), methanol fraction (MF) and methanol insoluble fraction (MIF) were prepared from bitter melon. An oral sucrose tolerance test revealed that administration of AE, MF or MIF each significantly suppressed plasma glucose levels at 30 min as compared with the control. In addition, the plasma insulin level at 30 min was also significantly lower after MF administration than in the control in the oral sucrose tolerance test. By contrast, these effects of bitter melon extracts were not observed in the oral glucose tolerance test. In terms of mechanism, bitter melon extracts dose-dependently inhibited the sucrase activity of intestinal mucosa with IC(50) values of 8.3, 3.7 and 12.0 mg/mL for AE, MF and MIF, respectively. The fraction with a molecular weight of less than 1,300 (LT 1,300) obtained from MF inhibited the sucrase activity most strongly in an uncompetitive manner with an IC(50) value of 2.6 mg/mL. Taken together, these results demonstrated that bitter melon suppressed postprandial hyperglycemia by inhibition of alpha-glucosidase activity and that the most beneficial component is present in the LT 1,300 fraction obtained from MF.

[Phosphorus intake and bone mineral density (BMD)].

Phosphorus regulates the bone formation and inhibits the bone resorption. It is still expected as one of anti-osteoporosis nutrients. The amounts of phosphorus intake with calcium are increasing from 1960 to 1995. Because phosphorus affects the regulation of calcium metabolism, the balance of these nutrients is important. Tuero suggested that more than 1,000 mg/day of calcium intake and more than 0.74 of Ca/P were associated with better bone mineral density (BMD) values in young women. However, there are few reports of correlations between appropriate phosphorus intake, Ca/P rate and BMD.

Stress control and human nutrition.

Stress is a pervasive factor in everyday life that critically affects development and functioning. Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. Brain food is aimed at preventing as well as treating a growing number of stress-related mental disorders. Some topics on the association of stress and nutrition is reviewed. (1) An increased activity of serotonergic neurons in the brain is an established consequence of stress. An increase in brain tryptophan levels on the order of that produced by eating a carbohydrate-rich/protein-poor meal causes parallel increases in the amounts of serotonin released into synapses. (2) Eating is thought to be suppressed during stress, due to anorectic effects of corticotrophin releasing hormone, and increased during recovery from stress, due to appetite stimulating effects of residual cortisol. (3) A strong inverse association between coffee intake and risk of suicide. (4) Night eating syndrome has been found to occur during periods of stress and is associated with poor results at attempts to lose weight and disturbances in the hypothalamic-pituitary-adrenal axis. (5) Dietary antioxidants present in fruits and vegetables may improve cognitive function. Therefore, it is concluded that the establishment of functional foods that correctly regulate stress response must be firmly based upon scientific knowledge and legal regulation.

Phosphorus supply per capita from food in Japan between 1960 and 1995.

The awareness of phosphorus intake is important because hyperphosphatemia and hypophosphatemia both impair bone metabolism. Phosphorus consumption from food was obtained from values in the Food Balance Sheet (PBS) of Japan from 1960 to 1995. The amounts of phosphorus calculated from the FBS increased gradually from 1,243 mg/d in 1960 to 1,332 mg/d in 1975 and to 1,421 mg/d in 1995. This is explained by the increased consumption of cow's milk and milk products, meat, and chicken eggs. The main foods supplying phosphorus in 1995 were cereals, milk and milk products, fishes and shellfishes, and vegetables; their contributions were 24.4, 15.8, 14.2, and 10.9%, respectively. The phosphorus-to-calcium ratio calculated from the FBS was 3.51 in 1960, which decreased to 2.89 in 1975 and 2.44 in 1995. Therefore total phosphorus consumption in 1995 was presumably more than 1,500 mg/d when imported food containing phosphorus and the consumption of phosphorus-containing food additives in Japan are also considered. These findings suggest that the phosphorus consumption estimated from the FBS is increasing and that more attention should be paid to the maintenance of healthy bones in Japan, where the average amount of calcium intake is less than 600 mg/d.