Role of Vitamins and Minerals in Health and Diseases.

We have adopted the following four topics: 1) dietary phosphorus management in chronic kidney disease (CKD) patients, 2) inadequate nutrient intakes in Filipino schoolchildren and adolescents, 3) clinical and societal implications of vitamin insufficiency, and 4) zinc transporters. Vitamins and minerals play essential roles in health promotion in clinical and societal perspectives with marked advances in understanding the mechanism underlying such effects.

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.

High-fat diets provoke phosphorus absorption from the small intestine in rats.

OBJECTIVE: The ratio of dietary carbohydrate to fat may affect phosphorus metabolism because both calcium and phosphorus are regulated by similar metabolic mechanisms, and a high-fat diet (HFD) induces deleterious effects on the absorption of dietary calcium. We hypothesized that an HFD induces an increase in phosphorus absorption. The aim of this study was to evaluate the effects of differences in the quantity and quality of dietary fat on phosphorus metabolism over the short- and long-term. METHODS: Eighteen 8-wk-old Sprague-Dawley male rats were fed an isocaloric diet containing varied ratios of carbohydrates to fat energy and sources of fat (control diet, HFD, and high- saturated fat diet [HF-SFA]). At 3 d and 7 wk after the allocation and initiation of the test diets, feces and urine were collected and used for phosphorus and calcium measurement. RESULTS: The fecal phosphorous concentration (F-Pi) was lower in the HF-SFA group than in the other two groups; however, the urine phosphorus concentration (U-Pi) was significantly higher in the HF-SFA group than the other two groups when the rats were fed over the short- (P < 0.01) and long -term (P < 0.01 versus control, P < 0.05 versus HFD group). There were no significant differences in type-IIa sodium-phosphate cotransporter (NaPi-2 a) and type-IIc sodium-phosphate cotransporter (NaPi-2 c) mRNA expression, which are renal phosphate transport-related genes; however, the expression of type-IIb sodium-phosphate cotransporter (NaPi-2 b) and type-III sodium-phosphate cotransporter (Pit-1) mRNA in the duodenum was higher in the HFD and HF-SFA groups than in the control group (P < 0.05), although there were no significant differences in these in the jejunum. CONCLUSIONS: The present results indicated that an HFD, particularly HF-SFA, increases intestinal phosphate absorption compared with control.

Management of phosphorus load in CKD patients.

Disturbances in mineral and bone metabolism play a critical role in the pathogenesis of cardiovascular complications in patients with chronic kidney disease (CKD). The term "renal osteodystrophy" has recently been replaced with "CKD-mineral and bone disorder (CKD-MBD)", which includes vascular calcification as well as bone abnormalities. In Japan, proportions of the aged and long-term dialysis patients are increasing which makes management of vascular calcification and parathyroid function increasingly more important. There are three main strategies to manage phosphate load: phosphorus dietary restriction, administration of phosphate binder and to ensure in the CKD 5D setting, an adequate dialysis.

Combination of n-3 polyunsaturated fatty acids reduces atherogenesis in apolipoprotein E-deficient mice by inhibiting macrophage activation.

BACKGROUND AND AIMS: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are major components of n-3 polyunsaturated fatty acids (n-3 PUFAs) which inhibit atherogenesis, although few studies have examined the effects of the combination of EPA and DHA on atherogenesis. The aim of this study was to investigate whether DHA has additional anti-atherosclerotic effects when combined with EPA. METHODS: Male 8-week-old apolipoprotein E-deficient (Apoe-/-) mice were fed a western-type diet supplemented with different amounts of EPA and DHA; EPA (2.5%, w/w), low-dose EPA + DHA (2.5%, w/w), or high-dose EPA + DHA (5%, w/w) for 20 weeks. The control group was fed a western-type diet containing no n-3 PUFA. Histological and gene expression analysis were performed in atherosclerotic lesions in the aorta. To address the mechanisms, RAW264.7 cells were used. RESULTS: All n-3 PUFA treatments significantly attenuated the development and destabilization of atherosclerotic plaques compared with the control. The anti-atherosclerotic effects were enhanced in the high-dose EPA + DHA group (p < 0.001), whereas the pure EPA group and low-dose EPA + DHA group showed similar results. EPA and DHA additively attenuated the expression of inflammatory molecules in RAW264.7 cells stimulated with LPS. DHA or EPA + DHA suppressed LPS-induced toll-like receptor 4 (TLR4) expression in lipid rafts on RAW264.7 cells (p < 0.05). Lipid raft disruption by methyl-ß-cyclodextrin suppressed mRNA expression of inflammatory molecules in LPS-stimulated macrophages. CONCLUSION: n-3 PUFAs suppressed atherogenesis. DHA combined with EPA had additional anti-inflammatory effects and inhibited atherogenesis in Apoe-/- mice. The reduction of TLR4 expression in lipid rafts in macrophages by DHA might be involved in this mechanism, at least partially.

[Key treatment of lifestyle-related diseases:nutritional education and practice].

In modern times, calcium and vegetable intake is known to be generally insufficient in the population. In addition, many patients increasingly have lifestyle-related diseases, such as obesity, and they require lifestyle modification to increase their energy consumption compared to their energy intake. Therefore, it is important for these patients to continue weight loss and to improve their dietary habits. The overall energy density (ED) of one's diet decreases by eating more vegetables and fruits. Moreover, higher vegetable intake contributes to an improvement in lifestyle as well as improves the calcium intake. In this article, we show that sufficient vegetable intake provides satiety and satisfaction.

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.

[Bone and Nutrition. A novel function of phosphorus].

Phosphorus is an essential nutrient for bone formation by forming hydroxyapatite with calcium. Simultaneously, phosphorus is also a component of high energy bond of ATP, nucleic acids, and phospholipids. Recent studies have demonstrated that excess or lack of dietary phosphorus intake may cause vascular dysfunction, cardiac hypertrophy, and impaired glucose tolerance. Here, we introduce recent findings about the effects of high or low dietary phosphorus intake on several organs except for bone.

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.

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

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.

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 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.