Shunsaku Mizushima

Effects of Oral Taurine Supplementation on Lipids and Sympathetic Nerve Tone

OBJECTIVESnTo assess effects of oral taurine supplementation on lipids and sympathetic nerve tone in healthy young men on experimental high fat and cholesterol diets.nnnMETHODSnTwenty-two healthy male volunteers, aged 18-29 years, were recruited for this randomized control trial after informed consent according to the Ethical Committee of Shimane Medical University. Volunteers were randomly allocated into 2 study groups and given experimental diet of identical regimen [total calorie 2500 kcal, cholesterol 1000 mg, polyunsaturated fat/saturated fat (P/S) ratio 0.52, fat 40% of total energy intake (%E), protein 14%E, carbohydrate 46%E] to raise serum cholesterol (CHO) level for 3 weeks. Alcohol intake, smoking and strenuous physical activities were prohibited. Taurine powder (6 g/day) was supplied to one group (T-group, N = 11) and placebo capsules to the other (C-group, N = 11), by a single-blind approach. Blood samples and 24 h urine specimens were obtained once every week. Two men in the C-group dropped out due to upper respiratory infection. There were no difference in age, body mass index (BMI) or blood pressure (BP) between the groups. Statistical analysis was performed by analysis of variance (ANOVA, repeated measurement) and Students t-test.nnnRESULTSnThere were no changes in BMI and BP in either group during the period. Significant increases in total CHO (25.4 +/- 17.5 mg/dl, mean +/- SD), LDL-CHO (17.1 +/- 14.5) and LDL (43.9 +/- 37.6) were observed in C-group but were attenuated in the T-group. The T-group showed significant increases in VLDL-CHO, VLDL and TG. The T-group had significantly lower urinary norepinephrine excretion than the C-group in the last week.nnnCONCLUSIONnOral taurine supplementation attenuated increases in T-CHO, LDL-CHO and LDL in healthy men on high fat cholesterol diets but induced significant increases in VLDL-CHO, VLDL and TG, which could be explained by a possible effect of taurine on lipoprotein lipase. Significantly lower urinary norepinephrine excretion observed by the taurine administration implies the suppression of the sympathetic nervous system.

Male cardiovascular mortality and dietary markers in 25 population samples of 16 countries.

Objective To examine associations between various dietary markers and mortality from ischemic heart disease (IHD) and stroke. Design and setting A multi-center cross-sectional study, involved 25 co-operative study centers in 16 countries. Method In the report, data for males (n = 2462), aged 48–56 years, from 25 centers were included. Various dietary markers were measured from individuals blood and 24-h urine samples. Age-standardized male mortality rates for IHD and stroke were collected for the region encompassing each study center. Ecological cross-center associations between dietary markers and the mortality were analyzed using univariate and multivariate analysis techniques. Results Bivariate correlation analyses showed that IHD mortality was associated positively with body mass index (BMI), serum total cholesterol (TC), urinary potassium (K) and serum phospholipid palmitic acid, and negatively with urinary taurine, sodium (Na) and Na/K (potassium) ratio, n-3 polyunsaturated (n-3PU) fatty acids and polyunsaturated-to-saturated (P/S) fatty acid ratio. Stroke mortality was associated positively with Na and Na/K ratio and phospholipid arachidonic acid (AA), and negatively with TC and K. Stepwise linear regression analyses indicated that 59% of the variance in IHD mortality could be explained by the variance in taurine and P/S ratio and that 57% of stroke mortality could be explained by Na/K ratio and phospholipid AA. Conclusion Although ecological associations do not necessarily imply causality, and the present findings are limited to male samples only, the study extends our understanding of dietary markers in relation to worldwide IHD and stroke mortality rates, and indicates useful avenues for further study on IHD and stroke prevention.

Fish Intake and Cardiovascular Risk Among Middle-Aged Japanese in Japan and Brazil:

Background Studies of immigrant populations are useful for analysis of the effects of environmental factors on cardiovascular disease. We have examined the association between dietary habit of fish intake and cardiovascular risk. Methods Population-based samples of 433 middle-aged Japanese men and women in Japan (Shimane (group JS) and Okinawa (group JO)) and 269 Japanese immigrants in Brazil (Sao Paulo (group BS) and Campo Grande (group BC)), who had originally moved to Brazil mainly from Shimane and Okinawa, were recruited to the study. They underwent blood pressure measurement, 24-h urine collection, blood tests and electrocardiographic examination, and completed a dietary questionnaire. Results There was a significant gradient through the groups, from JS to JO, BS and BC with respect to the prevalence of obesity, hypertension, increased glycohaemoglobin concentrations and ST-T segment change on the electrocardiogram (prevalences for men and women combined: Group JS 2.0%, group JO 3.8%, group BS 3.9% and group BC 9.0%; P< 0.025). The prevalence of hypercholesterolemia was noted more frequently in groups BS and BC. Twenty-four-hour urinary taurine excretion in both sexes and n-3 polyunsaturated fatty acids (n-3 PU FA) in plasma phospholipids in men were significantly higher in groups JS and JO than in groups BS and BC. A striking negative gradient in the frequency of fish intake per week was found from group JS (men/women, 4.7/4.8) to groups JO (3.8/3.6), BS (1.9/1.6) and BC (0.5/0.5). Conclusions This study suggests a possible association between fish intake and reduced cardiovascular risk, through the beneficial effects of taurine and n-3 PU FA and a habitual low intake of calories and fat.

Is Taurine a Preventive Nutritional Factor of Cardiovascular Diseases or Just a Biological Marker of Nutrition

For answering the question, “Is taurine a preventive nutritional factor of cardiovascular diseases (CVD) or just a biological marker of nutrition?” our experimental and world-wide cooperative studies on nutrition and CVD are reviewed. The data so far obtained indicates taurine is not only a good biological marker of sea food intakes but also an important nutrient for preventing hypertension and atherosclerosis.

Taurine as the nutritional factor for the longevity of the Japanese revealed by a world-wide epidemiological survey.

The initial observation that taurine (T) prevented stroke in stroke-prone spontaneously hypertensive rats (SHRSP) led us to study the effects of T on cardiovascular diseases (CVD), as well as the epidemiological association of T and mortality rates, by using the data from WHO-coordinated Cardiovascular Disease and Alimentary Comparison Study, which covered 61 populations in 25 countries. In this study, 24 hour urine (24-U) samples were examined along with biomarkers of CVD risk. The mortality rate from ischemic heart disease (IHD), which was lowest among the Japanese compared to the populations of other developed countries, was positively related to total serum cholesterol (TC) and inversely related to 24-U taurine excretion (24-UT), as well as the n-3 fatty acid to total phospholipids ratio of the plasma membrane, both biomarkers of seafood intake. Analysis of 5 diet-related factors revealed that TC and BMI were positively associated with IHD mortality in both genders while Mg and T were negatively associated with IHD mortality. TC and sodium (Na) were negatively and positively associated with stroke mortality, respectively. 24-UT was negatively associated with stroke mortality. These five diet-related factors explained 61 and 49% of IHD and stroke variances in male, 63 and 36% of IHD and stroke variances in female, respectively.

Different associations of blood pressure with 24-hour urinary sodium excretion among pre- and post-menopausal women

Objective Having found no definite relationship between blood pressure (BP) and 24h sodium excretion in women aged 48–56 years (in contrast to the results in men of the same age) in the WHO Cardiovascular Diseases and Alimentary Comparison (WHO-CARDIAC) Study, we analyzed the data to investigate whether the sodium–BP association differed between pre- and post-menopausal women. Design and methods The WHO-CARDIAC is a multi-center cross-sectional study, involving, as of July 2000, 60 collaborating centers in 25 countries. In each center, 100 men and 100 women aged 48–56 years were selected randomly from the general population of the area. In this report, 2212 women in 21 centers located in 17 countries worldwide, who had data on menopausal status, were studied. Results After adjustment for age, body mass index (BMI) and 24h urinary potassium excretion, 24h sodium excretion was positively and significantly associated with systolic blood pressure (SBP) [pooled regression coefficient: 0.037 (SE 0.01), P < 0.01] and with diastolic blood pressure (DBP) [0.023 (0.006), P < 0.01] in post-menopausal women. Pooled regression coefficients of sodium–BP association were not significant in pre-menopausal women (P < 0.05). Cross-center correlation analyses of the 21 centers showed that 24h sodium excretion was positively associated with SBP and DBP in both pre- and post-menopausal women, and this positive association between sodium excretion and SBP was significant in post-menopausal women (R2 = 0.23, P = 0.029). Conclusion Different associations between sodium and BP were observed in women with pre- and post-menopausal status. There may be a tendency for salt sensitivity to increase at the menopause.

Nutritional improvement, cardiovascular diseases and longevity in Japan.

Nutritional conditions have improved remarkably for the past 40 years in Japan; major improvements are increases in protein intake (69.7 in 1955 to 79. 2g/day per capita in ‘88), and fat intake (20.3 in ‘55 to 58.3 g/day per capita in ‘88), both of which are significantly related statistically to the gradual reduction of stroke mortality (r = –0.74, not significant; r = –0.78, p .05) and to a remarkable extension of average life span (r = 0.91, p 0.01; r = 0.98, p 0.001) in the Japanese. Average heights of 12-year old male and female children, correlating significantly with these nutritional improvements, are significantly positively correlated with average life spans (men and women respectively; r = 0.97, p 0.001). Thus, general nutritional improvements among the Japanese are regarded as the major contributory factor to the recent achievement of top-ranked position for longevity in the world.

A review of the link between dietary magnesium and cardiovascular risk.

1350-6277

An inverse association between magnesium in 24-h urine and cardiovascular risk factors in middle-aged subjects in 50 CARDIAC Study populations

Serum, plasma and dietary magnesium (Mg) have been reported to be inversely associated with cardiovascular disease risk factors. We examined the associations between the 24-h urinary Mg/creatinine (Cre) ratio and cardiovascular disease risk factors, such as body mass index (BMI), blood pressure (BP), serum total cholesterol (TC) and prevalence of obesity, hypertension and hypercholesterolemia. A cross-sectional analysis was conducted among 4211 participants (49.7% women) aged 48–56 years in 50 population samples from 22 countries in the World Health Organization-coordinated Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study (1985–1994). In linear regression analyses, Mg/Cre ratio was inversely associated with BMI, systolic BP (SBP), diastolic BP (DBP) and TC (P for linear trend <0.001 for each). These associations were not markedly altered by adjustment for traditional risk factors, urinary markers or cohort effects. Multivariate-adjusted mean values for the subjects in the highest Mg/Cre ratio quintile were 6.3, 3.4, 5.3 and 4.6% lower than those for the subjects in the lowest quintile for BMI, SBP, DBP and TC (P<0.001, respectively). The prevalence of obesity, hypertension and hypercholesterolemia was 2.10 (95% confidence interval: 1.50, 2.95), 1.55 (1.25, 1.92) and 2.06 (1.63, 2.62) times higher (P<0.001, respectively) among the subjects in the lowest Mg/Cre ratio quintile than in the subjects in the highest quintile. These associations were not appreciably altered by adjustment for potential confounding variables. In conclusion, higher 24-h urinary Mg/Cre ratio was associated with lower cardiovascular disease risk factors, including BMI, BP, TC, obesity, hypertension and hypercholesterolemia.

International Cooperative Study on the Relationship between Dietary Factors and Blood Pressure: a Preliminary Report from the Cardiovascular Diseases and Alimentary Comparison (Cardiac) Study

To investigate the epidemiological relationship of dietary factors to blood pressure (BP) and major cardiovascular diseases, we carried out the international cooperative Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, which so far involves 48 centers in 20 countries as of August 1991. From each population, 100 men and 100 women aged 50–54 years were randomly selected for BP measurement, 24-h urine collection, blood tests, and medical interview. Various biological markers of diets from urine and blood were analyzed centrally in the Izumo CARDIAC center. Cross center analysis using simple linear regression revealed strong significant correlations of body mass index (BMI) to systolic BP (SBP; p 0.01) and diastolic BP(DBP; p 0.001) in men. 24-h urinary sodium (Na) excretion in men also showed significant correlations with SBP (p 0.05) and DBP p 0.05) even after controling for the effect of BMI (SBP; p 0.05, DBP; p 0.05). Within center analysis using multiple linear regression implied that BMI and Na strongly adversely affect BP, whereas magnesium may have beneficial influence on BP. Multicolinearities among 24h urinary sodium, calcium, and urea nitrogen were noted in men.