Effects of dietary seaweed on obesity-related metabolic status: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Seaweed is a promising source of anti-obesity agents, including polysaccharides, proteins, polyphenols, carotenoids, and n-3 long-chain polyunsaturated fatty acids. The anti-obesity effects of such compounds may be due to several mechanisms, including inhibition of lipid absorption and metabolism, effect on satiety, and inhibition of adipocyte differentiation. OBJECTIVE: The aim of this study was to assess the evidence from human randomized controlled trials for the effects of seaweed on body-weight status as well as lipid and nonlipid parameters in adults with overweight and obesity. DATA SOURCES: Four databases-Medline, Scopus, Web of Science, and Cochrane Library-were searched from December 2022 to June 2023 using the following key words: Seaweed OR fucoxanthin OR alginates OR fucoidans OR phlorotannin's OR macroalgae OR marine algae AND obesity OR overweight OR BMI OR body mass index. DATA EXTRACTION: Eleven interventional studies (10 parallel and 1 crossover) were extracted. DATA ANALYSIS: Meta-analysis showed a significant effect, favoring the intervention group for BMI (body mass index) (standardized mean difference [SMD]: -0.40; 95% CI: -0.65 to -0.16 kg/m2; P = 0.0013) and percentage of fat mass (SMD: -1.48; 95% CI: -2.66% to -0.30%, P = 0.0138). The results were seen when refined or extracted brown seaweed (BMI) or only refined brown seaweed (% fat mass) were administered to participants for at least 8 weeks. Moreover, a significant overall effect of seaweed supplementation on total cholesterol (SMD: -7.72; 95% CI: -12.49 to -2.95 mg/dL; P = 0.0015) and low-density-lipoprotein cholesterol (SMD: -7.33; 95% CI: -11.64 to -3.02 mg/dL; P < 0.001) was noted. Any significant effects of seaweed on glucose metabolism were not shown. CONCLUSION: Edible seaweed supplementation shows potential for managing obesity and disorders of the blood lipid profile when administered to participants for at least 8 weeks. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022378484 (www.crd.york.ac.uk/PROSPERO).

Relationship between Regional Distribution of Centenarians and Drinking Water Hardness in the Amami Islands, Kagoshima Prefecture, Japan.

People who drink naturally hardened water may experience longevity-enhancing effects. In this study, we investigated water hardness and longevity from both geological and epidemiological perspectives in Japan's Amami islands, where drinking water is drawn from coralline or non-coralline bedrock. We investigated drinking water hardness, limestone bedrock occupancy, and the centenarian rate (number per 10,000 population) by municipality across four adjacent islands (Amami-Oshima (non-coralline), Tokunoshima, Okinoerabu, and Yoron (predominantly coralline)). Limestone was strongly correlated with water hardness (r = 0.99; p < 0.01), occupying more than 80% of the bedrock where the water was the hardest (Tokunoshima's Isen municipality: 86.5%; Yoron: 82.9%) and being scarcely detectable in Amami-Oshima (0.0 to 0.2%), where the water was the least hard. The centenarian rate was also strongly correlated with water hardness (r = 0.84, p < 0.01), with the highest figures in Yoron (29.7) and Isen (29.2), and the lowest in Amami-Oshima (0.0 to 12.2). Therefore, we hypothesize a potentially beneficial effect of hard water on longevity when that water is drawn from coralline limestone. Water hardness is determined by the water content of calcium and magnesium and may plausibly influence life expectancy through a preventative effect against cardiovascular disease. Our findings are of interest to current debates about future global access to drinking water and its quality.

Increased Glycine-conjugated and Unconjugated Bile Acid Levels Associated with Aggravation of Nonalcoholic Steatohepatitis and Cardiovascular Disease in SHRSP5/Dmcr Rat.

The SHRSP5/Dmcr is a useful animal model for the development of nonalcoholic steatohepatitis (NASH) pathology when fed a high-fat, high-cholesterol diet, and further drug interventions can lead to concomitant cardiovascular disease. While SHRSP5/Dmcr rats have been used for basic research related to NASH, details of their bile acid metabolism in this condition are unknown. In this study, we aimed to clarify the changes in the serum bile acid (BA) fractions associated with NASH and found that glycine-conjugated and unconjugated bile acid increased with worsening NASH and cardiovascular disease while taurine-conjugated BA relatively decreased.

Health Effects of Soy Isoflavones and Green Tea Catechins on Cancer and Cardiovascular Diseases Based on Urinary Biomarker Levels.

Plant polyphenols have various health effects. Genistein, which is abundant in soybeans, and epigallocatechin-3-gallate, which is abundant in green tea, are major flavonoids, a subclass group of polyphenols. Several epidemiological studies have shown that these flavonoids have beneficial effects against cancer and cardiovascular diseases. However, other studies did not show such effects. Several confounding factors, including recall bias, are related to these inconsistent findings, and the determination of metabolites in the urine may be useful in reducing the number of confounding factors. Equipment, which can be used by research participants to collect samples from a portion of voided urine within 24 h without the help of medical workers, has been developed for epidemiological investigations. Previous studies, in which flavonoid metabolites in these urine samples were measured, revealed that soy intake was correlated with a reduced risk of certain types of cancer and cardiovascular diseases worldwide. Although soybeans and green tea consumption may have protective effects against cancer and cardiovascular diseases, further clinical studies that consider different confounding factors are required to provide evidence for the actual impact of dietary flavonoids on human diseases, including cancer and cardiovascular diseases. One possible mechanism involved is discussed in relation to the downregulation of reactive oxygen species and the upregulation of 5'-adenosine monophosphate-activated protein kinase elicited by these flavonoids.

Stroke-Prone SHR as Experimental Models for Cardiovascular Disease Risk Reduction in Humans.

Since stroke-prone spontaneously hypertensive rats (SHRSP) develop hypertension and stroke without exception, the prevention or reduction of risk by various nutrients was tested on blood pressure and the mortality caused by stroke and cardiovascular diseases (CVD). In addition to sodium (Na) accelerating hypertension and stroke and potassium (K) counteracting the adverse effect of Na, taurine (Tau), rich in seafood, and magnesium (Mg) contained in soy, nuts, grains, etc., were proven to reduce stroke and CVD and improve survival. Therefore, the Cardiovascular Diseases and Alimentary Comparison Study was started in 1985 to explore the association of biomarkers of diet in 24 h urine (24U) with CVD risks, and about 100 males and 100 females aged 48-56 in each of 50 populations were studied until 1995. Linear regression analysis indicated that the 24U Tau/creatinine and Mg/creatinine ratios were inversely associated with body mass index, systolic and diastolic blood pressure, and total cholesterol. In comparison with six Euro-Western regions, 24U Tau and Mg collected from six regions, respectively, in Japan and the Mediterranean countries were significantly higher and were significantly associated with lower CVD risks. Diets rich in Tau and Mg were concluded to be contributory to the prevention of CVD in SHRSP and humans.

Analysis of spot urine biomarkers and association with body weight in Japanese elementary schoolchildren.

Childhood obesity is rapidly increasing worldwide and is largely the consequence of adoption of unhealthy diets excessive in calories and salt (NaCl) as well as devoid in pivotal micronutrients such as potassium (K) and magnesium (Mg). Education-based programs aiming to encourage healthy food knowledge and behaviors are crucial at a young age, and for this purpose, convenient ways to assess daily dietary intake are warranted. We therefore attempted to evaluate the dietary intake of Okinawan schoolchildren in Japan by analyzing a series of biomarkers in morning spot urine samples and explore whether these biomarkers correlate with body weight and a series of metabolic parameters. We enrolled 98 third-grade elementary schoolchildren in Okinawa, Japan. Morning spot urine samples were collected and analyzed using high-performance liquid chromatography (HPLC) to assess dietary intake. We found that estimated daily NaCl intake was higher in obese/overweight children as compared to healthy-weight children (p = 0.0001). There was also a significant positive correlation between body mass index (BMI) and NaCl intake (Spearman) (ρ = 0.45, p < 0.0001) and a negative correlation between BMI and Mg/Cr (ρ = -0.27, p = 0.01). Furthermore, Na/K ratio was higher in samples collected on Monday (weekend) as compared to samples collected on Thursday or Friday (weekday) (p < 0.0001). CONCLUSION: Via the use of morning spot urine analyses, our results show that NaCl intake was associated with obesity, and Mg excretion negatively correlated with BMI in Japanese schoolchildren, highlighting the potential role of these micronutrients in maintaining a healthy body weight. WHAT IS KNOWN: •Overweight and obesity are largely due to excessive consumption of calories and positively correlated with salt (NaCl) intake. •Spot urine methods are convenient for assessing the nutritional needs and targeting prevention programs in children. WHAT IS NEW: •Utilizing morning spot urine analyses, estimated NaCl intake is positively correlated and Mg/Cr negatively correlated with BMI in Okinawan schoolchildren. •As estimated via morning spot urine samples, a greater proportion of children likely exceeds the recommended NaCl intake on the weekend as compared to weekday.

Grading of Japanese Diet Intakes by 24-Hour Urine Analysis of Taurine and Soy Isoflavones in Relation to Cardiovascular Risks.

To investigate the association of the Japanese diet with risks for lifestyle-related diseases, the biomarkers of seafood and soybean consumption, taurine (T) and soy isoflavones (I), and others were analyzed in 24-hour urine (24U) samples collected from participants of the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study coordinated by the World Health Organization (WHO). The data of T and I normalized for creatinine content in 24U were divided into five quintiles, T1 to T5, and I1 to I5. The total data of the collected samples were divided into 25 groups, which were obtained by 5 (T1-T5) × 5 (I1-I5) according to 24U excretions of T and I corresponding to the intake of seafood and soybeans from the least to the highest, respectively. Since these two nutrients were often consumed together in the Japanese diet, this characteristic was expressed as J1 to J5 based on the amounts of 24U T and I excretions. The risks for lifestyle-related diseases, obesity (body mass index, BMI), and cholesterolemia became lower during the transition from J1 to J5, while HDL cholesterol levels became higher from J1 to J5. On the contrary, urinary salt excretion and the sodium (Na)/potassium (K) ratio became higher from J1 to J5. Systolic blood measure was significantly lower in J3 than in J5. Diastolic blood pressure was also significantly lower in J3 than in J1. In conclusion, the higher the J score, which corresponds to Japanese dietary habits, the lower the BMI and cholesterol levels, as well as mortality rate from coronary heart disease, but the higher the average life expectancy among the Japanese. However, these higher J scorings were associated with high-salt intake and high Na/K ratios; therefore, they contributed to high blood pressure and high mortality rate caused by stroke in Japan. These results indicate that low-salt intake should be recommended to the Japanese who are consuming seafood and soy regularly in order to maintain lower blood pressure and to extend healthy life expectancy with a lower risk of stroke. Moreover, high scorings of the Japanese diet correspond to the high intake of magnesium (Mg) which is rich in seafood including seaweeds and soy. Therefore, low-salt seafood and soy intake is expected to reduce the incidence of the metabolic syndrome, the risk of which is inversely related to T and Mg intake.

A Meta-Analysis of Randomized Controlled Trials of the Effects of Soy Intake on Inflammatory Markers in Postmenopausal Women.

BACKGROUND: Elevated concentrations of serum inflammatory cytokines, specifically TNF-α and IL-6, as well as C-reactive protein (CRP), are commonly observed after menopause. OBJECTIVES: Because soy isoflavones may have some anti-inflammatory potential, the aim of the present systematic review and meta-analysis of randomized controlled trials (RCTs) was to explore whether soy intake affects serum markers of inflammation in postmenopausal women. METHODS: PubMed, Web of Science, and the Cochrane Library were systematically searched up to August 2020. All RCTs that met the following criteria were included: 1) studies of the effects of soy intake on inflammatory markers; 2) any date of publication; 3) conducted on postmenopausal women; 4) with sufficient quantitative data for meta-analysis. Effect sizes were expressed as weighted mean differences (WMDs) and 95% CIs. A total of 24 RCTs assessing the effects of soy intake on serum concentrations of CRP, TNF-α, and IL-6 were included in the analysis. A random-effects model was used to determine the overall effect. RESULTS: Soy supplementation significantly reduced CRP by 0.11 mg/L in postmenopausal women (95% CI: -0.22, -0.004 mg/L; P = 0.0414), but did not affect IL-6 or TNF-α. Significant reductions in CRP concentration occurred when natural soy products were given (WMD: -0.23 mg/L; 95% CI: -0.29, -0.17 mg/L; P < 0.001). This is equivalent to a ∼9% reduction in CRP concentration from baseline. CONCLUSIONS: Although our meta-analysis found evidence that soy products significantly reduce CRP concentrations in postmenopausal women, the mechanisms by which soy foods and their constituents affect inflammatory biomarkers still need to be clarified.This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020179232.

Potential Effects of Soy Isoflavones on the Prevention of Metabolic Syndrome.

Isoflavones are polyphenols primarily contained in soybean. As phytoestrogens, isoflavones exert beneficial effects on various chronic diseases. Metabolic syndrome increases the risk of death due to arteriosclerosis in individuals with various pathological conditions, including obesity, hypertension, hyperglycemia, and dyslipidemia. Although the health benefits of soybean-derived isoflavones are widely known, their beneficial effects on the pathogenesis of metabolic syndrome are incompletely understood. This review aims to describe the association between soybean-derived isoflavone intake and the risk of metabolic syndrome development. We reviewed studies on soy isoflavones, particularly daidzein and genistein, and metabolic syndrome, using PubMed, ScienceDirect, and Web of Science. We describe the pathological characteristics of metabolic syndrome, including those contributing to multiple pathological conditions. Furthermore, we summarize the effects of soybean-derived daidzein and genistein on metabolic syndrome reported in human epidemiological studies and experiments using in vitro and in vivo models. In particular, we emphasize the role of soy isoflavones in metabolic syndrome-induced cardiovascular diseases. In conclusion, this review focuses on the potential of soy isoflavones to prevent metabolic syndrome by influencing the onset of hypertension, hyperglycemia, dyslipidemia, and arteriosclerosis and discusses the anti-inflammatory effects of isoflavones.

Altered Properties of Neurons and Astrocytes and the Effects of Food Components in Stroke-Prone Spontaneously Hypertensive Rats.

ABSTRACT: In stroke-prone spontaneously hypertensive rats (SHRSP), stroke induces neuronal vulnerability and neuronal death, while astrocytes show a weakened support function toward neurons. Moreover, certain food components have been demonstrated to prevent the occurrence of stroke. This review aims to explain the stroke-related properties of SHRSP-derived neurons and astrocytes. In addition, it describes the effects of particular dietary phytochemicals on SHRSP. In this study, we obtained information using PubMed, ScienceDirect, and Web of Science. We searched for the functions of neurons and astrocytes and the molecular mechanism of ischemic stroke induction. We summarized the recent literature on the underlying mechanisms of stroke onset in SHRSP and the alleviating effects of typical food-derived phytochemical components. Neuronal death in SHRSP is induced by hypoxia-reoxygenation, suggesting the involvement of oxidative stress. Furthermore, the production of lactate, l-serine, and glial cell line-derived neurotrophic factor in SHRSP-derived astrocytes was reduced compared with that in control Wistar-Kyoto rats. Vitamin E exerts an inhibitory effect on hypoxia-reoxygenation-induced neuronal death in SHRSP. Curcumin, epigallocatechin gallate, resveratrol, and carotenoids can prevent the development of stroke in SHRSP. In particular, the properties of SHRSP-derived neurons and astrocytes affect stroke-induced neuronal death. This review suggests the potential and therapeutic applications of dietary phytochemicals in reducing stroke risk and lowering blood pressure in SHRSP, respectively, by targeting various processes, including oxidative stress, apoptosis, and inflammation. Thus, future research on SHRSP brain cells with a genetic predisposition to stroke can consider using these food ingredients to develop approaches for stroke prevention.

Bile acids aggravate nonalcoholic steatohepatitis and cardiovascular disease in SHRSP5/Dmcr rat model.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is linked to an increased risk of cardiovascular disease, regardless of the risk factors in metabolic syndrome. However, the intermediary factors between NASH and cardiovascular disease are still unknown. A previous study revealed that serum and hepatic bile acid (BA) levels are increased in some NASH patients. We aimed to examine whether NASH and cardiovascular disease were aggravated by BA using an animal model. METHOD AND RESULTS: From 10 to 18 weeks of age, SHRSP5/Dmcr rats divided into 3 groups were fed 3 types of high-fat and high-cholesterol (HFC) diets which were changed in the cholic acid (CA) concentration (0%, 2%, or 4%). The nitro oxide synthase inhibition (L-NAME) was administered intraperitoneally from 16 to 18 weeks of age. The 4% CA groups showed the worst LV dysfunction and myocardial fibrosis, and demonstrated severe hepatic fibrosis and lipid depositions. In addition, a large amount of lipid accumulation was observed in the aortas of the 4% CA group, and NFκB and VCAM-1 gene expression levels were increased. These findings were not seen in the 0% CA group. CONCLUSION: In the SHRSP5/Dmcr rat model, NASH and cardiovascular disease were aggravated with increasing BAs concentrations in an HFC diet.

Inhibition of Endothelial Dysfunction by Dietary Flavonoids and Preventive Effects Against Cardiovascular Disease.

Cardiovascular disease (CVD), such as stroke, ischemic heart disease, and heart failure, accounts for many deaths, and its increasing incidence is a worldwide concern. Accumulating evidence suggests that the elevated risk of CVD caused by dysfunction of vascular endothelial cells and resultant arteriosclerosis can be mitigated by increased consumption of fruits and vegetables. These foods contain phytochemicals such as polyphenols and carotenoids, as well as dietary fiber. Flavonoids of the polyphenol class are found in vegetables, fruits, grains, bark, roots, stems, flowers, tea, and wine. Several studies have indicated that flavonoids reduce CVD mortality by inhibiting endothelial dysfunction. Flavonoids have a common carbon skeleton and are classified as flavonols, flavones, flavanols, flavanones, anthocyanidins, and isoflavones. In this review, we discuss recent progress in identifying the mechanisms by which dietary flavonoids improve vascular endothelial cell function. Furthermore, we describe the beneficial role that these flavonoids may play in preventing CVD caused by endothelial dysfunction-related atherosclerosis.

Bile acid detoxifying enzymes limit susceptibility to liver fibrosis in female SHRSP5/Dmcr rats fed with a high-fat-cholesterol diet.

During middle age, women are less susceptible to nonalcoholic steatohepatitis (NASH) than men. Thus, we investigated the underlying molecular mechanisms behind these sexual differences using an established rat model of NASH. Mature female and male stroke-prone spontaneously hypertensive 5/Dmcr rats were fed control or high-fat-cholesterol (HFC) diets for 2, 8, and 14 weeks. Although HFC-induced hepatic fibrosis was markedly less severe in females than in males, only minor gender differences were observed in expression levels of cytochrome P450 enzymes (CYP)7A1, CYP8B1 CYP27A1, and CYP7B1, and multidrug resistance-associated protein 3, and bile salt export pump, which are involved in fibrosis-related bile acid (BA) kinetics. However, the BA detoxification-related enzymes UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) 2A1, and the nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR), were strongly suppressed in HFC-fed males, and were only slightly changed in HFC-diet fed females. Expression levels of the farnesoid X receptor and its small heterodimer partner were similarly regulated in a gender-dependent fashion following HFC feeding. Hence, the pronounced female resistance to HFC-induced liver damage likely reflects sustained expression of the nuclear receptors CAR and PXR and the BA detoxification enzymes UGT and SULT.

The effects of fermented milk containing Lactococcus lactis subsp. cremoris FC on defaecation in healthy young Japanese women: a double-blind, placebo-controlled study.

The objective of this double-blind, placebo-controlled study was to elucidate the effects of fermented milk containing Lactococcus lactis subsp. cremoris FC (FC) on defaecation in healthy young women. We included 31 women (18-31 years old) who were randomly selected into two groups. Subjects in the test group consumed fermented milk containing FC, while subjects in the placebo group consumed non-fermented gelled milk. In the test group, defaecation frequency (both in days and times per week) and stool volume significantly increased during the consumption of fermented milk containing FC compared with before consumption. These effects were also observed in subjects with mild constipation. Furthermore, in subjects with mild constipation, stool ammonia concentration was significantly lower in the test group than that in the placebo group after 4 weeks. These results suggest that fermented milk containing FC is beneficial for improving defaecation and faecal properties.

A High-Fat and High-Cholesterol Diet Induces Cardiac Fibrosis, Vascular Endothelial, and Left Ventricular Diastolic Dysfunction in SHRSP5/Dmcr Rats.

AIM: Non-alcoholic steatohepatitis (NASH) increases cardiovascular risk regardless of risk factors in metabolic syndrome. However, the intermediary factors between NASH and vascular disease are still unknown because a suitable animal model has never been established. The stroke-prone (SP) spontaneously hypertensive rat, SHRSP5/Dmcr, simultaneously develops hypertension, acute arterial lipid deposits in mesenteric arteries, and NASH when feed with a high-fat and high-cholesterol (HFC) diet. We investigated whether SHRSP5/Dmcr affected with NASH aggravates the cardiac or vascular dysfunction. METHOD: Wister Kyoto and SHRSP5/Dmcr rats were divided into 4 groups of 5 rats each, and fed with a SP or HFC diet. After 8 weeks of HFC or SP diet feeding, glucose and insulin resistance, echocardiography, blood biochemistry, histopathological staining, and endothelial function in aorta were evaluated. RESULTS: We demonstrate that SHRSP5/Dmcr rats fed with a HFC diet presented with cardiac and vascular dysfunction caused by cardiac fibrosis, endothelial dysfunction, and left ventricular diastolic dysfunction, in association with NASH and hypertension. These cardiac and vascular dysfunctions were aggravated and not associated with the presence of hypertension, glucose metabolism disorder, and/or obesity. CONCLUSIONS: SHRSP5/Dmcr rats may be a suitable animal model for elucidating the organ interaction between NASH and cardiac or vascular dysfunction.

Non-alcoholic steatohepatitis aggravates nitric oxide synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rat model.

Non-alcoholic steatohepatitis (NASH) is linked to increased cardiovascular risk, independent of the broad spectrum of metabolic syndrome risk factors. Stroke-prone (SP) spontaneously hypertensive rats (SHRSP5/Dmcr) fed a high-fat and high-cholesterol (HFC) diet developed hepatic lesions similar to those in human NASH pathology. These rats simultaneously developed lipid deposits in the mesenteric arteries, cardiac fibrosis, endothelial dysfunction and left ventricle (LV) diastolic dysfunction. However, the intermediary factors between NASH and cardiovascular disease are still unknown. We investigated whether NASH aggravates nitric oxide (NO) synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rats. Wistar Kyoto and SHRSP5/Dmcr rats were divided into 4 groups of 5 and fed the stroke-prone (SP) or HFC diets for 8 weeks. To induce NO synthase inhibition, Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME) mixed with drinking water was administered in the final 2 weeks. The NASH+L-NAME group demonstrated the following characteristics related to arteriosclerosis and myocardial ischaemia: (a) LV systolic dysfunction with asynergy, (b) replacement fibrosis caused by the shedding of cardiomyocytes and (c) arterial lipid deposition and coronary occlusion secondary to endothelial dysfunction. These characteristics were not observed in the NASH or non-NASH+L-NAME groups. The SHRSP5/Dmcr rat model demonstrates that NASH significantly aggravates cardiovascular risk.

Natural compound bavachalcone promotes the differentiation of endothelial progenitor cells and neovascularization through the RORα-erythropoietin-AMPK axis.

In cardiovascular diseases, endothelial function is impaired and the level of circulating endothelial progenitor cells (EPCs) is low. This study investigated whether the natural bioactive component bavachalcone (BavaC) induces the differentiation of EPCs and neovascularization in vivo; the underlying mechanisms were also examined. We observed that the treatment of rat bone marrow-derived cells with a very low dose of BavaC significantly promoted EPC differentiation. In our hindlimb ischemia models, low-dose BavaC administered orally for 14 days stimulated the recovery of ischemic hindlimb blood flow, increased circulating EPCs, and promoted capillary angiogenesis. The BavaC treatment of rat bone marrow cells for 24 h initiated the AMP-activated protein kinase (AMPK) activity required for the differentiation of EPCs. Further testing revealed that BavaC and CGP52608, a retinoic acid receptor-related orphan receptor α (RORα) activator, enhanced the activity of RORα1 and EPO luciferase reporter gene. BavaC treatment also elevated EPO mRNA and protein expression in vitro and in vivo and the circulating EPO levels in rats. By contrast, the RORα antagonist VPR66 inhibited BavaC-induced EPO reporter activity, and differentiation of bone marrow cells into endothelial progenitor cells. Overall, this study revealed that BavaC promotes EPC differentiation and neovascularization through a RORα-EPO-AMPK axis. BavaC can be used as a promising angiogenesis agent for enhancing angiogenesis and tissue repair.

Correction: Soy and fish as features of the Japanese diet and cardiovascular disease risks.

[This corrects the article DOI: 10.1371/journal.pone.0176039.].

Taurine Intake with Magnesium Reduces Cardiometabolic Risks.

WHO-CARDIAC (Cardiovascular Diseases and Alimentary Comparison) Study revealed the quintile analyses of 24-h urinary (24 U) taurine (T) and magnesium (Mg) excretions were inversely related with cardiometabolic risks (CMR) such as obesity, hypertension and hypercholesterolemia in 50 population samples in the world. To exclude the influence of ethnicity in the study, 24 U T and Mg excretions were analyzed for the association with CMR in one ethnicity, Japanese population.24 U T/creatinine (C) ratios were divided into 5 quintiles and the ratios of Japanese to the total of each quintile were analyzed from CARDIAC Study samples. The highest 24 U T quintile consisted of 60% Japanese, indicating high seafood consumption in Japanese.Over 600 Japanese aged 30-79 were invited to a health examination for blood pressure measurement and for fasting blood and 24 U samplings. Tertile analysis of 24 U T/C ratios in relation to CMR indicated the third tertile had significantly higher HDL cholesterol, 24 U potassium (K) and 24 U salt than the first (lowest) tertile. Tertile analysis of 24 U Mg/C ratios indicated the third tertile had significantly lower body mass index and significantly higher folic acid, 24 U isoflavones, K and salt than the first tertile after age and gender adjustment. The third tertile of both T/C and Mg/C had significantly lower body mass index, LDL/HDL and Na/K ratios, and significantly higher HDL cholesterol and folic acid than the first tertile, indicating seafood eaters taking Mg rich diets had lower risks of obesity, atherosclerosis, hypertension and higher folic acid, beneficial for healthy longevity.

Soy and fish as features of the Japanese diet and cardiovascular disease risks.

In the World Health Organization (WHO)-coordinated Cardiovascular Disease and Alimentary Comparison Study, isoflavones (I; biomarker for dietary soy) and taurine (T; biomarker for dietary fish) in 24-hour-urine (24U) were inversely related to coronary heart disease (CHD) mortality. High levels of these biomarkers are found in Japanese people, whose CHD mortality is lowest among developed countries. We analyzed the association of these biomarkers with cardiovascular disease risk in the Japanese to know their health effects within one ethnic population. First, to compare the Japanese intake of I and T with international intakes, the ratios of 24UI and 24UT to creatinine from the WHO Study were divided into quintiles for analysis. The ratio for the Japanese was the highest in the highest quintiles for both I and T, reaching 88.1%, far higher than the average ratio for the Japanese (26.3%) in the total study population. Second, 553 inhabitants of Hyogo Prefecture, Japan, aged 30 to 79 years underwent 24-U collection and blood analyses. The 24UT and 24UI were divided into tertiles and adjusted for age and sex. The highest T tertile, compared with the lowest tertile, showed significantly higher levels of high-density lipoprotein-cholesterol (HDL-C), total cholesterol, 24U sodium (Na) and potassium (K). The highest I tertile showed significantly higher folate, 24UNa and 24UK compared with the lowest tertile. The highest tertile of both T and I showed significantly higher HDL-C, folate, and 24UNa and 24UK compared with the lowest tertile. Thus, greater consumption of fish and soy were significantly associated with higher HDL-C and folate levels, possibly a contributor to Japan having the lowest CHD mortality and longest life expectancy among developed countries. As these intakes were also associated with a high intake of salt, a low-salt intake of fish and soy should be recommended for healthy life expectancy.