Does the Protective Effect of Zinc on Telomere Length Depend on the Presence of Hypertension or Type 2 Diabetes? Results from the Iwaki Health Promotion Project, Japan.

Telomeres, repeated TTAGGG sequences at chromosomal ends, shorten with age and indicate cellular lifespan. Zinc can protect against telomere damage through its anti-oxidative effect. Meanwhile, telomere shortening was correlated with metabolic diseases of hypertension and type 2 diabetes. The objective of this study was to investigate whether the association between zinc and telomere length differs by the presence or absence of hypertension/type 2 diabetes. This is a cross-sectional study with 1064 participants of the Iwaki area, Japan. Multiple linear regression models were performed to test the hypothesis. A higher serum zinc concentration was significantly associated with a longer G-tail length (ß = 48.11, 95% confidence intervals [CI]: 25.69, 70.54, p < 0.001). By multivariate linear regression analysis, there was a significant positive association between zinc and G-tail length in both hypertensive (ß = 46.84, 95%CI: 9.69, 84.0, p = 0.014) and non-hypertensive groups (ß = 49.47, 95%CI: 20.75, 78.18, p = 0.001), while the association was significant only in the non-diabetes group (ß = 50.82, 95%CI: 27.54, 74.11, p < 0.001). In conclusion, higher zinc concentration was significantly associated with longer G-tail length. The protective effect of zinc on G-tail did not differ by hypertension status; however, it disappeared in individuals with type 2 diabetes.

Intake of 25-Hydroxyvitamin D3 May Reduce the Severity of Upper Respiratory Tract Infection: Post hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Parallel Group Comparison Study.

To evaluate the effects of 25-hydroxyvitamin D3 (25OHD) on symptoms at the onset of the upper respiratory tract infection (URTI) in subjects with insufficient or deficient serum 25-hydroxyvitamin D levels, we conducted a post hoc analysis of data from a randomized, placebo-controlled study; the subjects received 10 µg of 25OHD per day or a placebo for 16 weeks. The Wisconsin Upper Respiratory Symptom Survey-21 was used to determine URTI. The study endpoints included WURSS-21 scores, number of URTI events, and proportion of medication (antibiotics, antipyretic analgesics) usage. We found that the physical symptom scores for "Runny nose," "Sneezing," and "Head congestion" were significantly lower in the 25OHD group than in the placebo group; for all items except "Breathe easily, "the quality of life" scores were significantly improved in the 25OHD group. There was no significant difference in the number of URTI events or the proportion of medication use between the groups. Collectively, the findings of this study indicate that a sufficient 25OHD intake can reduce physical symptoms at the onset of upper respiratory tract infection, particularly nasal symptoms, and may improve the quality of life at the time of onset.

Oral Ingestion of Collagen Hydrolysate Leads to the Transportation of Highly Concentrated Gly-Pro-Hyp and Its Hydrolyzed Form of Pro-Hyp into the Bloodstream and Skin.

Collagen hydrolysate is a well-known dietary supplement for the treatment of skin aging; however, its mode of action remains unknown. Previous studies have shown that the oral ingestion of collagen hydrolysate leads to elevated levels of collagen-derived peptides in the blood, but whether these peptides reach the skin remains unclear. Here, we analyzed the plasma concentration of collagen-derived peptides after ingestion of high tripeptide containing collagen hydrolysate in humans. We identified 17 types of collagen-derived peptides transiently, with a particular enrichment in Gly-Pro-Hyp. This was also observed using an in vivo mouse model in the plasma and skin, albeit with a higher enrichment of Pro-Hyp in the skin. Interestingly, this Pro-Hyp enrichment in the skin was derived from Gly-Pro-Hyp hydrolysis, as the administration of pure Gly-Pro-Hyp peptide led to similar results. Therefore, we propose that functional peptides can be transferred to the skin by dietary supplements of collagen.

Rice Bran Extract Reduces the Risk of Atherosclerosis in Post-Menopausal Vietnamese Women.

We investigated whether pre-germinated brown rice bran extract containing acylated steryl glucosides (PSG) reduces the risk of atherosclerosis in post-menopausal Vietnamese women. A total of 60 post-menopausal Vietnamese women (45-65 y old) with high LDL cholesterol levels (over 140 mg/dL) were randomly divided into PSG (n=30) and placebo (n=30) groups. The subjects in the PSG group were assigned a daily intake of 6 capsules containing 50 mg PSG, and the subjects in the placebo group were assigned a daily intake of 6 capsules containing corn oil for 6 mo. Before baseline and after month 2, month 4, and month 6 of the intervention, we conducted anthropometric measurements, blood biochemical examinations, a nutrition survey, and physical activity, flow-mediated dilation (FMD), and cardio-ankle vascular index (CAVI) measurements. Serum LDL cholesterol concentrations were significantly reduced from 163.6±25.3 (mg/dL) to 135.9±26.8 (mg/dL) compared to the placebo group (p<0.001). FMD values of the placebo group were significantly reduced from 6.6±5.1 (%) to 4.7±2.6 (%) compared to the PSG group (p<0.05). Tumor necrosis factor (TNF)-α concentrations in the PSG group were significantly reduced from 19.8±11 (pg/mL) to 10.6±5.5 (pg/mL) compared to the placebo group (p<0.05). The findings suggest that PSG may improve LDL cholesterol, TNF-α levels, and FMD values. PSG might be considered in reducing the risk of atherosclerosis in post-menopausal Vietnamese women with high LDL cholesterol.

Systemic administration of resveratrol suppress the nociceptive neuronal activity of spinal trigeminal nucleus caudalis in rats.

Although a modulatory role has been reported for the red wine polyphenol resveratrol on several types of ion channels and excitatory synaptic transmission in the nervous system, the acute effects of resveratrol in vivo, particularly on nociceptive transmission of the trigeminal system, remain to be determined. The aim of the present study was to investigate whether acute intravenous resveratrol administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from 18 SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was inhibited by resveratrol (0.5-2 mg/kg, i.v.) and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 10 min. These inhibitory effects were reversed after approximately 20 min. The relative magnitude of inhibition by resveratrol of SpVc WDR neuronal discharge frequency was significantly greater for noxious than non-noxious stimulation. These results suggest that, in the absence of inflammatory or neuropathic pain, acute intravenous resveratrol administration suppresses trigeminal sensory transmission, including nociception, and so resveratrol may be used as a complementary and alternative medicine therapeutic agent for the treatment of trigeminal nociceptive pain, including hyperalgesia.

Rice bran extract containing acylated steryl glucoside fraction decreases elevated blood LDL cholesterol level in obese Japanese men.

People who frequently consume whole grains show a lower incidence of arteriosclerotic disease than people who consume primarily refined grains. We examined whether or not rice bran extract containing the acylated steryl glucosides (ASG) fraction decreases blood LDL cholesterol levels in obese Japanese men with high blood levels of LDL cholesterol. The study utilized a randomized, double-blind design. A total of 51 subjects were randomly allocated to either a rice bran extract containing ASG fraction (RB-ASG) group or a placebo group. Subjects in the RB-ASG group received 30-50 mg/day of RB-ASG, and the placebo group took 9 capsules/day for 12 weeks. Before and after intake, height, weight, body fat percentage, systolic and diastolic blood pressure were measured, blood was collected, and visceral fat area, subcutaneous fat area, and abdominal circumference were determined based on umbilical computed tomography. Percentage decreases in blood LDL cholesterol, non-HDL cholesterol, LDL/HDL ratio, abdominal circumference and subcutaneous fat area were significantly better in the RB-ASG group than in the placebo group. These findings suggest that RB-ASG fraction may reduce blood LDL cholesterol levels and the risk of arteriosclerosis in obese Japanese men with high LDL cholesterol levels.

Effects of L-serine ingestion on human sleep.

To investigate the effects of L-serine intake on human sleep, we conducted two randomized double-blinded crossover studies. In Study 1, healthy subjects who were dissatisfied with their sleep were given L-serine or a placebo 30 min before going to bed. After waking the next morning, subjective sleep quality was rated using the Ogri-Shirakawa-Azumi subjective sleep rating scale. In Study 2, subjective sleep quality was rated using the St. Mary's Hospital sleep questionnaire, and objective parameters, including sleep initiation time, number of nighttime awakenings, and hours of sleep, were evaluated using actigraphy. In Study 1, factors related to "sleep initiation" and "sleep maintenance" during the L-serine intake period were significantly improved compared to the placebo intake period (p = 0.02 and p = 0.008, respectively). In Study 2, scores for "How well did you sleep last night?" and "How satisfied were you with last night's sleep?" were significantly better during L-serine intake compared to placebo (p = 0.04 and p = 0.03, respectively). Subjective evaluation of sleep quality on waking was thus improved. In addition, objective evaluation using actigraphy showed that the "number of nighttime awakenings" tended to be decreased (p = 0.08). These findings suggest that intake of L-serine before going to bed may improve human sleep.

Pre-germinated brown rice reduced both blood glucose concentration and body weight in Vietnamese women with impaired glucose tolerance.

We have reported that newly diagnosed type 2 diabetes mellitus (DM) patients in Vietnam have a low body mass index (BMI) of around 23 and that the major factor for this is high white rice (WR) intake. Brown rice (BR) is known to be beneficial in the control of blood glucose levels; however, it has the property of unpleasant palatability. Pre-germinated brown rice (PGBR) is slightly germinated by soaking BR in water as this reduces the hardness of BR and makes it easier to eat. This study was designed to evaluate the effect of a 4-mo PGBR administration on various parameters in Vietnamese women aged 45-65 y with impaired glucose tolerance (IGT). Sixty subjects were divided into a WR or PGBR group. For the first 2 wk, WR was replaced by 50% PGBR, then for 2 wk by 75% PGBR and from the second month 100%. Before the beginning of the study and at the end of the study, 1) anthropometric measurements, 2) a nutrition survey for 3 nonconsecutive days by the 24 h recall method and 3) blood biochemical examinations were conducted. Fasting plasma concentrations of glucose and lipids and the obesity-related measurements and blood pressure were favorably improved only in the PGBR diet group. The present results suggest that replacing WR with PGBR for 4 mo may be useful in controlling body weight as well as blood glucose and lipid levels in Vietnamese women with IGT.

Replacing white rice with pre-germinated brown rice mildly ameliorates hyperglycemia and imbalance of adipocytokine levels in type 2 diabetes model rats.

Pre-germinated brown rice (PR) has been developed industrially in order to enhance the nutritional functions of its source material, brown rice (BR). The present study was aimed at clarifying the effect of PR on the type 2 diabetes mellitus. We employed Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a model of type-2 diabetes mellitus. OLETF rats were fed on either PR or white rice (WR) from the age of 4 to 35 wk. Age-matched male Long-Evans Tokushima Otsuka (LETO) rats as a non-diabetic control were also fed on WR. The HbA(1c) level in OLETF rats was significantly higher than that in LETO rats. However, the level was lower in PR-fed OLETF rats than in WR-fed OLETF rats. The plasma concentrations of TNF-α and PAI-1 in OLETF rats were higher than those in LETO rats. However, both elevated levels were decreased by the PR-feeding, but not by the WR-feeding. On the other hand, the plasma adiponectin concentration in OLETF rats was lower than that in LETO rats. The decrease in adiponectin level of OLETF rats was ameliorated by PR-feeding. The size of adipocytes in PR-fed OLETF rats was smaller than that in WR-fed OLETF rats. In summary, intake of PR instead of WR ameliorates both insulin resistance and imbalance of the levels of plasma adipocytokines leading to diabetic complications.

Effects of pre-germinated brown rice on blood glucose and lipid levels in free-living patients with impaired fasting glucose or type 2 diabetes.

White rice (WR) is made by polishing brown rice (BR) and has lost various nutrients; however, most people prefer it to BR, maybe because of the hardness of BR. Pre-germinated brown rice (PGBR) improves the problem of BR. It is made by soaking BR kernels in water to germinate and becomes softer than BR. In this study we compared the effects of WR and PGBR on blood glucose and lipid concentrations in the impaired fasting glucose (IFG) or type 2 diabetes patients. Six men and 5 women with impaired fasting glucose (IFG) or type 2 diabetes were randomly allocated to 6 wk on WR or PGBR diet separated by a 2 wk washout interval in a crossover design. Each subject was instructed to consume 3 packs of cooked WR or PGBR (180 g/pack) daily in each intervention phase. Blood samples were collected 4 times (in study weeks 0, 6, 8 and 14) for biochemical examination. Blood concentrations of fasting blood glucose, fructosamine, serum total cholesterol and triacylglycerol levels were favorably improved on the PGBR diet (p<0.01), but not on the WR diet. The present results suggest that diets including PGBR may be useful to control blood glucose level.

Effect of pre-germinated brown rice intake on diabetic neuropathy in streptozotocin-induced diabetic rats.

BACKGROUND: To study the effects of a pre-germinated brown rice diet (PR) on diabetic neuropathy in streptozotocin (STZ)-induced diabetic rats. METHODS: The effects of a PR diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with those fed brown rice (BR) or white rice (WR) diets with respect to the following parameters: blood-glucose level, motor-nerve conduction velocity (NCV), sciatic-nerve Na+/K+-ATPase activity, and serum homocysteine-thiolactonase (HTase) activity. RESULTS: Compared with diabetic rats fed BR or WR diets, those fed a PR diet demonstrated significantly lower blood-glucose levels (p < 0.001), improved NCV (1.2- and 1.3-fold higher, respectively), and increased Na+/K+-ATPase activity (1.6- and 1.7-fold higher, respectively). The PR diet was also able to normalize decreased serum homocysteine levels normally seen in diabetic rats. The increased Na+/K+-ATPase activity observed in rats fed PR diets was associated with elevations in HTase activity (r = 0.913, p < 0.001). The in vitro effect of the total lipid extract from PR bran (TLp) on the Na+/K+-ATPase and HTase activity was also examined. Incubation of homocysteine thiolactone (HT) with low-density lipoprotein (LDL) in vitro resulted in generation of HT-modified LDL, which possessed high potency to inhibit Na+/K+-ATPase activity in the sciatic nerve membrane. The inhibitory effect of HT-modified LDL on Na+/K+-ATPase activity disappeared when TLp was added to the incubation mixture. Furthermore, TLp directly activated the HTase associated with high-density lipoprotein (HDL). CONCLUSION: PR treatment shows efficacy for protecting diabetic deterioration and for improving physiological parameters of diabetic neuropathy in rats, as compared with a BR or WR diet. This effect may be induced by a mechanism whereby PR intake mitigates diabetic neuropathy by one or more factors in the total lipid fraction. The active lipid fraction is able to protect the Na+/K+-ATPase of the sciatic-nerve membrane from the toxicity of HT-modified LDL and to directly activate the HTase of HDL.

Hypocholesterolemic action of pre-germinated brown rice in hepatoma-bearing rats.

The effect of pre-germinated brown rice (PGBR) on cholesterol metabolism was studied in Donryu rats subcutaneously implanted with the ascites hepatoma cell line AH109A and compared with that of white rice (WR). The effect of brown rice (BR), the source of PGBR, was also studied. Hepatoma-bearing rats fed a WR diet exhibited hypercholesterolemia compared with normal rats fed the same diet. Feeding hepatoma-bearing rats a PGBR or BR diet suppressed hepatoma-induced hypercholesterolemia, and enhanced fecal bile acid excretion and the activity of cholesterol 7alpha-hydroxylase, the rate-limiting enzyme of bile acid biosynthesis, in the microsomal fraction of the liver without affecting cholesterol synthesis in the host liver of hepatoma-bearing rats. These results suggest that PGBR as well as BR suppresses hypercholesterolemia induced by hepatoma growth by up-regulating cholesterol catabolism.

Postprandial blood glucose and insulin responses to pre-germinated brown rice in healthy subjects.

Effects of pre-germinated brown rice (PGBR) on postprandial blood glucose and insulin concentrations were compared with brown rice (BR) and white rice (WR) in two studies. In the first study, we investigated the time course of postprandial blood glucose and insulin concentrations after ingesting 25% (W/V) glucose solution, PGBR, BR or WR in 19 healthy young subjects. In the second study, dose-dependent effect of PGBR on the time course of postprandial blood glucose concentrations was compared among 4 different mixtures of PGBR and WR in 13 healthy young subjects. They were solely PGBR, 2/3 PGBR (PGBR: WR = 2 : 1), 1/3 PGBR (PGBR : WR = 1 : 2) and solely WR. Each sample was studied on a different day. The samples were selected randomly by the subjects. All the rice samples contained 50 g of available carbohydrates. The previous day the subjects ate the assigned dinner by 9:00 pm and then were allowed only water until the examination. The next morning, they ingested each test rice sample with 150 ml of water in 5-10 min. Blood was collected into capillary tubes from finger at 0, 30, 60, 90 and 120 min after the ingestion. The incremental areas under the curve (IAUC) of blood glucose concentrations (IAUC-Glc) for 120 min after the administration of PGBR and BR were lower than those after WR. In contrast the IAUC-Glc of BR and PGBR were not different (Study 1). The higher the ratio of PGBR/WR, the lower the glycemic index became (Study 2). These results suggest that intake of PGBR instead of WR is effective for the control of postprandial blood glucose concentration without increasing the insulin secretion.

Insoluble fiber is a major constituent responsible for lowering the post-prandial blood glucose concentration in the pre-germinated brown rice.

The intake of pre-germinated brown rice (PR) instead of white rice (WR) ameliorates the hyperglycemia. To clarify the mechanism(s) to decrease the post-prandial blood glucose concentration, the effect of water-soluble/oil-soluble fraction-depleted PR bran (termed as "DB"; which is destarched and defatted PR bran) on post-prandial blood glucose was compared with that of full-fat PR bran (PB) or WR. The test diets, WR diet, PB diet and DB diet which are containing identical amount of available carbohydrate (1.5 g) were fed to Wistar strain rats. Post-prandial blood glucose concentration and incremental area under the curve (IAUC) for DB diet were lower than those for WR diet, and there was no difference between the DB diet and PB diet. Changes in plasma insulin concentration and the IAUC obtained also revealed the same tendency as those observed in blood glucose concentration. These results indicate that the blood glucose-lowering effect of PB diet may be derived from the properties of PB involving substantially higher content of dietary fiber than WR, and that the potential benefit of intake of PR instead of WR in the prevention of diabetic vascular complications.

Effects of pre-germinated brown rice on beta-amyloid protein-induced learning and memory deficits in mice.

We evaluated the effects of pre-germinated brown rice (hatsuga genmai, PGR) on learning and memory and compared them with those of polished rice or cornstarch. In mice that were fed pellets of polished rice or PGR for two weeks, the learning ability in the Morris water maze test was significantly enhanced compared with mice that were fed cornstarch pellets. In the Y-maze test, the intake of food pellets for two weeks failed to affect spontaneous alternation behavior. Beta-amyloid(25-35) (Abeta(25-35): 3 nmol/mouse, i.c.v.) protein impaired spontaneous alternation behavior in mice that were fed pellets of cornstarch or polished rice. In contrast, PGR pellets prevented the Abeta(25-35)-induced impairment of spontaneous alternation behavior. These results suggest that polished rice and PGR have facilitating effects on spatial learning. In particular, it is surmised that PGR may prevent Alzheimer's disease associated with Abeta.

Exercise training increases membrane bound form of tumor necrosis factor-alpha receptors with decreases in the secretion of soluble forms of receptors in rat adipocytes.

We examined the effects of exercise training (treadmill running over 9 weeks) on the ability of isolated adipocytes to secrete tumor necrosis factor-alpha (TNF-alpha) and type 1 soluble TNF receptor (sTNFR1) in vitro in Wistar rats. We also examined the effects of exercise training on the expression of membrane bound forms of type 1 TNF receptor (mTNFR1) in adipocyte crude membranes of the same rat subjects. Exercise training significantly increased the secretions of TNF-alpha from isolated adipocytes. Treatment with a cyclooxygenase inhibitor, either indomethacin (100 microM) or eicosatetraynoic acid (100 microM), significantly blocked the release of TNF-alpha from adipocytes in both exercise-trained rat group and sedentary control rat group, suggesting that some cyclooxygenase metabolite(s) acts as a ligand in TNF-alpha synthesis. Decreased amounts of TNF-alpha were found to be significantly greater in both exercise-trained rat group than in sedentary control rat group after incubation with inhibitors. Thus, the inhibitory effect of both indomethacin and eicosatetraynoic acid was significantly greater in adipocytes from exercise-trained rats. Both plasma sTNFR1 levels and adipocytes-derived sTNFR1 were found to be significantly less in the exercise-trained rat group. Western blot analysis revealed that exercise training remarkably increased the expressions of mTNFR1 in adipocyte crude membrane. Thus, exercise training enhanced the ability of isolated adipocytes to secrete TNF-alpha with reduced secretion of sTNFR1, and provoked the greater expressions of mTNFR1 in adipocyte crude membrane. These alterations may induce enhanced the autocrine effects of TNF-alpha within adipocytes in exercise-trained rats.