To explore the effect of vitamin A supplements on iron metabolic homeostasis for preschoolers. This was a randomized, placebo-controlled and blinded intervention trial with 3- to 6-y old preschoolers. A total of 445 subjects were randomly divided into four groups: a vitamin A supplementation group (group 1, a single oral dose of vitamin A as retinol 200,000 IU), an iron supplement group (group 2, daily oral supplement with the elemental iron 1-2 mg/kg/d for 5 d a week, lasting for 6 mo) a combined vitamin A and iron (group 3) and administration of no vitamin A or iron as a placebo-control (group 4). A total of 387 (95, 98, 90 and 104 from groups 1, 2, 3 and 4) children completed the intervention. After intervention, serum retinol levels of children in group 1 and group 3 was markedly higher than those of children in groups 2 and 4 (p<0.05). The serum ferritin level of children in group 1 significantly decreased after intervention (p<0.05), but increased in group 2 (p<0.05). The sTfR-SF index (TFR-F) and total body iron content (BTIC) showed the same change after intervention. In group 2 and group 3, the levels of TRF-F index and BTIC had statistically increased to the same degree after intervention (p<0.05). The impact of vitamin A intervention on iron metabolic homeostasis was mainly manifested in storage and mobilization; there was no direct effect on total body iron content or iron absorption in the intestine.
In those with the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, enzyme activity is lowered. Therefore, these individuals might require an increased intake of folate to maintain or control blood levels of plasma folate or total homocysteine (tHcy). We examined associations of dietary folate intake with fasting plasma folate and total homocysteine (tHcy) according to genotype among 554 Japanese (207 men and 347 women aged 39-89 y) recruited in 2009. Intake of folate was estimated with a food frequency questionnaire. The MTHFR polymorphism was genotyped by a polymerase chain reaction with confronting two-pair primers. The log-transformed concentration of folate or tHcy was regressed on energy-adjusted folate intake in a linear regression analysis. Higher folate intake was associated with higher plasma folate among those with the CC (β=0.165, p=0.066) or CT (β=0.248, p<0.001) genotypes, and with lower tHcy levels only among those with the CC (β=−0.141, p=0.013) genotype. Plasma folate was significantly and inversely associated with tHcy, irrespective of MTHFR genotype. When the analysis was restricted to those with tHcy levels higher than the reference range (≥13.5 nmol/mL, n=20), these significant associations were not found. The interaction between folate intake or plasma folate and genotype was not significant in any analysis. In conclusion, dietary folate intake was positively associated with plasma folate among those with the CC or CT genotypes and inversely associated with tHcy among those with the CC genotype, but the associations were not clear among those with higher levels of tHcy.
Recently, there has been an increasing concern about noncommunicable diseases (NCDs), in which oxidative damage plays a role. In this paper, we have re-analyzed the data from the National Health and Nutrition Survey (NHNS) 2007 to study the relationship between an NCD (e.g. hypertension) and the dietary intake of vitamin E, a potent anti-oxidative vitamin. The inclusion criteria were those aged 40 and over, excluding pregnant or lactating women, and data from 1,405 males and 2,102 females were analyzed. The mean ages were 63.5 and 62.4, respectively. Nutrients intake was evaluated from a semi-weighted, 1-d household dietary record. When the subjects were categorized into tertiles based on their vitamin E intake, higher vitamin E intake was associated with a lower percentage of subjects with hypertension (p for trend=0.01). Subjects with higher vitamin E intake had higher energy intake-adjusted intake of other nutrients which have been considered to be related to hypertension such as potassium, magnesium, and vitamin C. Logistic regression analysis was done with the low tertile of vitamin E intake as the reference. The medium and high tertiles of vitamin E intake were associated with a significantly lower odds ratio for hypertension, 0.73 (95% CI; 0.62-0.87) for the former and 0.81 (95% CI; 0.69-0.96) for the latter. Additional analyses, one adjusted for the indices associated with hypertension and one excluding the subjects with vitamin E supplementation, have yielded the similar results. In summary, re-analysis of data from NHNS has revealed that higher vitamin E intake was significantly associated with lower prevalence of hypertension.
A standardized simple, indirect method for assessing the relative energy of dietary fiber carbohydrates is not yet established. There is a need for a standardized in vivo assay. The objective of the present study was to evaluate the relative available energy (RAE) for 9 major dietary fiber materials (DFMs) based on fermentability from breath hydrogen excretion (BHE) in subjects. Fructooligosaccharide (FOS) was used as a reference. The study was conducted using a within-subject, repeated measures design and approved by the Ethical Committee of University of Nagasaki. After DFM ingestion, end-expiratory gas (750-mL) was collected at 1-h intervals for 8 h, as well as at 2-h intervals between 8 h and 14 h, and 30 min after waking up and 24 h after DFM ingestion. Breath hydrogen concentration was assessed with a gas chromatograph. The RAE of DFMs tested was evaluated based on the area under the curve (AUC) of BHE of FOS. Based on the ratio of AUC for 8 h, the RAE of polydextrose, partially hydrolysed guar gum, resistant maltodextrin and partially hydrolysed alginate was 1 kcal/g, and that of glucomannan, heat-moisture treatment and high-amylose cornstarch and cellulose was 0 kcal/g, while the RAE of all tested DEMs including cellulose and glucomannan was 1 kcal/g in the calculation based on AUCs for 14 h and 24 h in subjects. We suggest that a breath hydrogen collection period of 14 h or more could be used to measure RAE for a range of fiber preparations in vivo.
We have previously reported that dietary supplementation with up to 5.0 g/d of L-tryptophan (L-Trp) for 21 d has no adverse effects, judging from the levels of general blood variables, in healthy women. We performed a randomized, double-blind, placebo-controlled, crossover intervention study in 17 apparently healthy Japanese women. The subjects were randomly assigned to receive a placebo (0 g/d) or 1.0, 2.0, 3.0, 4.0, or 5.0 g/d of L-Trp for 21 d each with a 5-wk washout period between trials. We examined the 24-h urine profiles on days −1 (1 d before starting L-Trp), 7, 14, and 21 to determine whether administration of L-Trp at doses of up to 5.0 g/d affects time-dependent urinary excretion of L-Trp or its metabolites in healthy women. The urinary excretion of L-Trp, kynurenic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide increased in an L-Trp dose-dependent manner on day 7. The amount of urinary excretion of these compounds was unchanged on days 14 and 21. The urinary excretion of serotonin, 5-hydroxyindole-3-acetic acid, 2-oxoadipic acid, and nicotinamide was unaffected by L-Trp at any of the doses tested. L-Trp doses had weak effects on the urinary excretion of kynurenine and anthranilic acid. Based on these findings, we conclude that there are no time-dependent effects of L-Trp administration in urinary excretion of L-Trp metabolites. Additionally, L-Trp and its metabolites do not accumulate in the body.
The adverse effects of D-tryptophan and the possibility of it being a surrogate index for predicting adverse effects in rats were investigated. Male rats were fed one of several test diets (20% casein diets with 0% (control), 0.1%, 0.2%, 0.3%, 0.4%, and 0.5% D-tryptophan) for 21 d, and 24-h urine samples on the final day of the experiment were collected. Analyses of food intake and body-weight changes revealed adverse effects to be observed in the group fed the 0.3% D-tryptophan diet. We propose urinary levels of 3-hydroxykynurenine/3-hydroxyanthranilic acid to be surrogate indicators for predicting the adverse effects of D-tryptophan from the break point of body-weight gains and urinary levels of D-tryptophan metabolites. The reaction 3-hydroxykynurenine→3-hydroxyanthranilic acid is catalyzed by the pyridoxal phosphate-dependent enzyme kynureninase. Increasing urinary 3-hydrokykynurenine indicates kynureninase deficiency. Intake of D-tryptophan in rats fed the 0.3% D-tryptophan diet was 0.21 g/kg body weight and feeding of the 0.3% D-tryptophan diet did not elicit adverse effects. Thus, the safe level of D-tryptophan was less than 0.2% in the diet, 0.15 g/kg body weight, in rats.
The association between vitamin D deficiency in the first trimester and GDM development remains controversial in various ethnicities. We prospectively assessed whether pregnant women with vitamin D deficiency during early pregnancy had an increased likelihood of GDM development or poor fetal growth or pregnancy outcomes compared to those with sufficient vitamin D levels. Serum 25-OH-D measurements and fetal ultrasonograms were carried out at 12-14, 20-22, and 32-34 wk in 523 pregnant women. Each woman was screened for GDM at 24-28 wk. There were no differences in serum 25-OH-D levels at 12-14 wk or 22-24 wk of pregnancy between GDM and non-GDM women after adjusting for maternal age, BMI at prepregnancy, BMI at first visit, BMI at GDM screening, gestational age at sampling, previous history of GDM, vitamin D intake, and seasonal variation in sampling. The risk of GDM, insulin resistance, and impaired β-cell function had no association with serum 25-OH-D levels in crude or adjusted logistic regression analysis. GDM was not associated with maternal serum 25-OH-D deficiency during the first trimester or fetal growth during the first and second trimesters. Pregnancy outcomes such as miscarriage, Apgar 1, Apgar 5 and birth weight were independent of maternal serum 25-OH-D levels during the first, second and third trimester of pregnancy. In conclusion, neither GDM prevalence nor fetal growth during pregnancy is associated with vitamin D deficiency at the first trimester in Korean women. Pregnancy outcomes are also independent of maternal vitamin D status.
Androgen-dependent prostate cancer inevitably progresses to incurable castration-resistant prostate cancer (CRPC) after androgen deprivation therapy. Because castration-induced hypoxia-inducible factor (HIF)-1α enhances the transcriptional activity of androgen receptor (AR) at low androgen levels mimicking the castration-resistant stage, HIF-1α is expected to be a promising target for suppression of growth of CRPC. We investigated the effect of resveratrol (3,4′,5-trihydroxy-trans-stilbene) on the growth of human prostate cancer LNCaP xenografts in castrated male BALB/cSlc-nu/nu mice (5 wk old). The mice were administered a control diet or a resveratrol diet (4 g/kg diet) for 40 d. The resveratrol diet significantly suppressed tumor growth compared to the control diet. In LNCaP xenografts, dietary resveratrol decreased the protein level of HIF-1α, but not the AR coactivator β-catenin, and reduced the mRNA levels of androgen-responsive genes. In the control group, β-catenin was predominantly localized in the nucleus with HIF-1α in LNCaP xenografts, whereas dietary resveratrol inhibited the nuclear accumulation of β-catenin. In hypoxic LNCaP cells at a low androgen level mimicking the castration-resistant stage, hypoxia-induced nuclear accumulation of β-catenin was inhibited by resveratrol. Furthermore, resveratrol repressed the expression level of HIF-1α even in the presence of a proteasome inhibitor and suppressed hypoxia-enhanced AR transactivation. These results indicate that dietary resveratrol represses nuclear localization of β-catenin by decreasing the HIF-1α expression, perhaps in a proteasome-independent manner, and inhibits β-catenin-mediated AR signaling; this contributes to suppression of tumor growth of CRPC.
Enzyme-treated asparagus extract (ETAS) has been developed as a novel anti-stress functional food ingredient that is produced from asparagus. Two human intervention trials with ETAS were conducted in healthy adult male volunteers. Study 1 was a randomized, double-blind, placebo-controlled study to assess the effects of ETAS on expression of heat shock protein 70 (HSP70) mRNA in blood and the autonomic nervous system (ANS). The ETAS group showed a tendency to enhance HSP70 mRNA expression level compared to the placebo group. Several ANS condition parameters were significantly improved in the ETAS group when compared to the placebo group. In Study 2, a randomized, double-blind, placebo-controlled, crossover trial investigated the influence on stress-related hormones and sleep. Serum and salivary cortisol levels were significantly elevated compared to baseline during the placebo period, but remained unchanged during the ETAS period. The salivary chromogranin A level was significantly decreased in the ETAS-treated subjects compared to their baseline levels. The actual sleep time was not significantly different between ETAS and placebo. However, when the subjects were divided into two categories based on sleep efficiency or the average of night sleeping time, ETAS intake was effective to modulate the sleep state among those with low sleep efficiency or excess sleep time.
S-Equol is enantioselectively produced from the isoflavone daidzein by gut microflora and is absorbed by the body. An increase of pancreatic β-cell death is directly associated with defects in insulin secretion and an increased risk of type 2 diabetes mellitus. In the present study, we demonstrate that only the S-enantiomer has suppressive effects against alloxan-induced oxidative stress in INS-1 pancreatic β-cells. S-Equol reduced alloxan-induced cell death in a dose-dependent manner, whereas R-equol had no effects. In contrast, no significant differences were observed between the enantiomers in estrogenic activity. The cytoprotective effects of S-equol were stronger than those of its precursor daidzein and were blocked by the protein synthesis inhibitor cycloheximide. The cytoprotection was diminished when cells were incubated with a protein kinase A (PKA) inhibitor (H89), but not an estrogen receptor inhibitor. S-Equol increased intracellular cAMP levels in an enantioselective manner. S-Equol, but not R-equol, induced phosphorylation of cAMP-response element-binding protein at Ser 133, and induced cAMP-response element-mediated transcription, both of which were diminished in the presence of H89. Taken together, these results show that S-equol enantioselectively increases the survival of INS-1 cells presumably through activating PKA signaling. Thus, S-equol might have applications as an anti-type 2 diabetic agent.
D-Sorbose is naturally occurring rare sugar. In this study, we examined the effects of dietary D-sorbose in rats. Four-week-old male Sprague-Dawley rats were fed either an AIN-93G-based control diet or a 3% D-sorbose diet for 28 d. Body weight and body fat accumulation were not different between the two diet groups. Dietary supplementation of D-sorbose lowered the serum insulin level (*p<0.05) significantly compared to the control, although the glucose was not changed. In addition, the relative weight of the cecum increased significantly in the D-sorbose group (**p<0.01). These findings suggest that intake of D-sorbose may improve the glucose metabolism by reducing insulin secretion, and D-sorbose can be used as a food ingredient.
Rice has storage proteins, e.g., glutelin, globulin and prolamin, in the seeds, which are used as nitrogen sources during germination. Rice prolamin has been reported to be an indigestible protein that decreases the nutritional value of rice. However, the causes for the indigestibility of prolamin are currently not clear. The objective of this study was to determine if prolamin is naturally indigestible or if cooking affects its digestibility. The gastrointestinal (GI) transit of rice 23 kDa glutelin (23G) and 13 kDa prolamin (13P) in Wistar/ST rats fed raw rice (RR) and cooked rice (CR) diets was assessed using Western blot analysis. We also measured the excretion of these proteins in the feces of these rats. Additionally, morphological observation of the structure of type-I protein bodies in the feces was performed using electron microscopy. Assessment of GI transit revealed that 23G rapidly disappeared from the GI contents of both the RR and CR groups, but 13P accumulated in the cecum of the CR group. In the CR group, prolamin, maintaining the structure of PB-I, was fully excreted in the feces. These results indicate that rice prolamin is not indigestible by nature, but is rendered indigestible by cooking.