Abstracts of Journal of Japanese Society for Magnesium Research Volume 23, Number 2, 2004

ARTICLE

The effects on health status by drinking water made from deep sea water without salt – The reduction of plasma cholesterol by drinking water made from deep sea water without salt

Takeda Research Institute of Life Science and Preventive Medicine 

The effects of the westernizing of food habits and lack of exercise on health status reflecting the urbanisation of daily life in Japan are examined. With these changes of life habits, protein and lipid intakes are increasing, and minerals and vitamin intakes are decreasing. So, the number of people with elevated serum cholesterol concentrations is increasing and they are at an increased risk of developing atherosclerosis and coronary artery disease. On the other hand, the role of magnesium (Mg) in the prevention of this disease by improving lipid metabolism is well-known. But in Japan, with the westernizing of food habits, fish, vegetable and algae intakes are also decreasing, and Mg intake is lowering. We tried to prevent atherosclerosis and coronary artery disease by drinking the naturally Mg-rich drink «deep sea water» made from deep sea water without salt. The effects of oral «deep sea water» on the lipid metabolism of rats were studied. The «deep sea water» was made from deep sea water by removing NaCl and preparing concentration (mg/L): 1) control: distilled water (Mg < 1 mg/L, Ca < 1 mg/L); 2) Mg200 (Mg 200 mg/L, Ca 67 mg/L); 3) Mg600 (Mg 600 mg/L, Ca 200 mg/L); 4) Mg1000 (MG 1000 mg/L, Ca 333 mg/L). 
Male Wistar rats weighing about 90 g were fed synthetic diets and for drinking, distilled water and the above three kinds of «deep sea water» were provided ad libitum for 4 weeks. After 4 weeks, blood samples were taken from a ventral aorta. Twenty five plasma biochemical analyses were conducted. The physiological behavior, food intake and water consumption in the rats were not significantly different in each group. Pathological changes were also not found. In the plasma biochemical data, total cholesterol values in the plasma of rats who drank 2 kinds of high Mg concentration «deep sea water» (Mg600 and Mg1000) resulted in a significant decrease compared to rats who drank distilled water (control group). These results suggest that «deep sea water» may be a useful natural drink to improve lipid metabolism and to prevent atherosclerosis and coronary artery disease. 

Key words: magnesium, drinking water, deep sea water, plasma cholesterol 

Bone fracture, serum magnesium and haemoglobin in elderly inpatients

Noboru Saito¹, Naoto Tabata², Yoshihisa Ando², Shinya Otani¹, Saburou Saito¹, Akihiro Iwamitu³, Yukiko Onaga³, Tuyoshi Hori³, Harumi Sayama⁴, Toshiko Kawakita⁴  

¹ Department of Internal Medicine and Center for Lifestyle-related Diseases; 
² Department of Surgery and Center for Alimentary Tract and Liver Diseases; 
³ Department of Internal Medicine and Center for Alimentary Tract and Liver Diseases, Miyazaki Medical Center Hospital; 
⁴ Department of cardiovascular Diseases, Kyoto Prevention Medical Center 

This study aimed to clarify the relationships among bone fractures, serum magnesium (Mg), calcium (Ca), albumin (Alb), zinc (Zn) and hemoglobin (Hb). Elderly inpatients of both sexes were recruited, who suffered mainly from cerebral infarction, had below 30 mg/dL of blood urea nitrogen and were not being administered furosemid. In this study, 286 inpatients (105 men, 181 women) were divided into two groups: patients given MgO and patients without MgO. Three kinds of bone fractures were investigated: fractures of the long bone (FLB), fractures of vertebrae (FV) and fragility fractures. As the controls 157 inpatients (72 men, 85 women) without bone fractures (FB(-)) were recruited. In 14 males with FLB serum Mg and Hb were significantly lower compared to 41 males with FB(-). Even with administration of MgO for treating constipation, serum Mg was lower significantly in FLB, MgO compared to FB(-), MgO in either males or females. In 36 females with FLB serum Mg, Alb, Ca and Hb were significantly lower compared to 56 females with FB(-). With administration of MgO, serum Mg became significantly higher in females with FLB, MgO compared to females with FLB. In cases with FV no significant difference of serum Mg was detected compared to cases with FB(-). In a comparison of 14 males with FLB and 41 males with FB(-), serum Mg and Hb were significantly lower in males with FLB. In a comparison of 36 females with FLB and 56 females with FB(-), serum Mg, Ca, Alb and Hb were significantly lower in females with LB, and were associated with higher age and lower BMI. In 12 cases (2 men, 10 women), mean age 87.6 years, who were complicated with fragility fracture, serum Mg, Zn and Hb were significantly lower compared to 12 sex- and age-matched controls with FB(-). 
In conclusion serum Mg and Hb decreased in cases with FLB. 

Key words: fracture of long bone, fragility fracture, serum magnesium, serum albumin, hemoglobin 

Effect of Mg concentration in the medium on osteoblast proliferation

Isao Hirata and Masayuki Okazaki 

Graduate School of Biomedical Sciences, Hiroshima University 

Each osteoblast proliferation rate was almost constant below 20 mM of magnesium, and was then inhibited dramatically with the increase of magnesium concentration in the medium solution. At 100 mM Mg concentration, the proliferation rate descended to one-third of that in control medium, originally including 0.81 mM. 

Key words: Mg concentration, osteoblast 

Quantitative analysis of Mg²⁺ extrusion transport in rat ventricular myocytes

Masato Konishi, Pulat Tursun and Michiko Tashiro 

Department of Physiology, Tokyo Medical University 

We previously reported that Mg^2 +  efflux from rat ventricular myocytes could be induced after Mg²⁺ loading of the cells (Tashiro et al., Jpn J Physiol 2002; 52: 541-51). In that study, we loaded the cells with the fluorescent Mg²⁺ indicator furaptra (mag-fura-2) using its AM ester form, and measured the indicator fluorescence in Ca²⁺-free conditions at 25^oC. However, quantitative interpretation of the results is not straightforward, because a part of the furaptra molecules may be trapped inside organelles after AM-loading. Experiments were therefore carried out to examine the possible contribution of the fluorescence signals emitted from the organelles. When the cell membrane of furaptra-loaded myocytes were permeabilized with saponin (25 μg/mL for 5 m), furaptra fluorescence intensity at 350 nm excitation decreased to 22 ± 3.8%; about 78% of furaptra fluorescence appeared to report cytoplasmic [Mg²⁺] ([Mg²⁺]_c) while residual 22% likely represented [Mg²⁺] in organelles (primarily mitochondria as revealed by fluorescence imaging). [Mg²⁺] calibrated from the residual furaptra fluorescence ([Mg²⁺]_r) was 0.6-0.7 mM at bath [Mg²⁺] (i.e., [Mg²⁺]_c of the skinned myocytes) of either 0.8 mM or 4.0 mM, suggesting that [Mg²⁺]_r was lower than and virtually insensitive to [Mg²⁺]_c. Because changes in [Mg²⁺]_c were probably underestimated in the previous study, we corrected [Mg²⁺] values measured in intact myocytes for this insensitive fraction of fluorescence to estimate [Mg²⁺]_c. In addition, we calculated changes in total Mg²⁺ concentration to get quantitative information on Mg²⁺ flux across the cell membrane by utilizing concentration and dissociation constant values of known cytoplasmic Mg²⁺ buffers. The relation between [Mg²⁺]_c and Mg²⁺ flux thus obtained suggest that Mg²⁺ extrusion is steeply regulated by [Mg²⁺]_c above the basal level with half maximal activation at 1.9 mM and the maximal rate of 5.5 μM/s. 

Key words: Mg²⁺ extrusion, cardiomyocyte, rat 

Gene expressions related to growth in skeletal muscle of magnesium-deficient rats

Tohru Matsui, Hiroshi Kobayashi, Hiroyuki Kawachi, Hideo Yano 

Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University 

We investigated gene expressions related to growth in skeletal muscle of magnesium-deficient rats. The expression of α-actin and myosin heavy chain mRNAs tended to decrease in magnesium-deficient rats but magnesium deficiency did not affect myostatin mRNA expression, which suggests that magnesium deficiency suppresses muscular protein synthesis without affecting myostatin gene expression. Magnesium deficiency stimulated MyoD mRNA expression. The increase in MyoD mRNA suggests the proliferation of muscular satellite cells, which may be caused by regeneration of muscle in lesions induced by magnesium deficiency. 

Key words: growth, skeletal muscle, magnesium, rat 

Effect of low magnesium diet on bone metabolism in rats

Shin-Ichi Katsumata¹, Hiroshi Matsuzaki², Mariko Uehara¹, Kazuharu Suzuki¹  

¹ Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture; 
² Department of Nutrition, Junior College of Tokyo University of Agriculture 

It is known that magnesium (Mg) deficiency induces bone loss accompanied with a decrease in bone formation and an increase in bone resorption. In this study, we investigated the effect of low Mg diet on bone metabolism in rats. Serum osteocalcin concentration was decreased and urinary excretion of CTx was increased in rats fed low Mg diets (0.025 and 0.01% Mg). The low Mg diets decreased serum insulin-like growth factor (IGF)-1 concentration and increased serum soluble receptor activator of nuclear factor-κB ligand (sRANKL) concentration. These results suggested that low Mg diet might cause a decrease in serum IGF-1 concentration and an increase in serum sRANKL concentration, which suppressed bone formation and enhanced bone resorption, respectively. 

Key words: magnesium, bone, osteocalcin, rat 

Loss of potassium(K), magnesium(Mg), and calcium(Ca) during cooking of foods

Izumi Osawa, Akio Kobayashi, Norihiro Ide 

Graduate School of Home Life Science, Tokyo Kasei-Gakuin University, Department of Laboratory Medicine, Showa University Toyosu Hospital, Tokyo 

We determined the loss of K, Mg and Ca during cooking (boiling and soaking) of several fresh vegetables. Spinach was boiled in 1000ml of water at 90-95 for 1, 2, and 7minutes. The concentration of K in boiling water after cooking was 2.9, 4.0, and 7.1 mEq/l, respectively. That of Mg was 1.4, 2.3, and 3.0 mg/dL, and of Ca 0.10, 0.15, and 0.17 mg/dL, respectively. 

Key words: cooking, spinach, loss of minerals 

Nutritional status of people in Japanese prison, especially Magnesium and other mineral levels in blood

M. Ikegawa¹, N. Koizumi², T. Yamashita³, M. Imanishi³,T. Takeda¹, M. Kimura¹  

¹ Kyoto Prefectural University of Medicine, Dept. of Genomic Medical Sciences; 
² Kyoto Detention House; 
³ Takeda Research Institute of Life Science 

We have been working on the health of people in Japanese prisons, especially from the nutritional viewpoint. As we have pointed out, effective diet control delivered to a good standard while in custody, even for a short period, can make a significant contribution to the health of individuals suffering from diabetes, hypertension and chronic liver diseases. However, there is still much more to be done around the country for the improvement of diet in prisons, as well as improving prisoners’ capacity to benefit from them. To monitor the health status of 49 men and 6 women, total 55 people, in Kyoto Detention House, blood samples were taken from them with informed consent and the results were fed back to them. Magnesium (Mg), calcium Ca), sulfur (S), iron (Fe), phosphorus (P), zinc (Zn), copper (Cu) and strontium (Sr) concentrations in blood were determined by inductively coupled plasma-atomic emission spectrometry, as well as biochemical and hematological tests. Blood vitamin B1 (Vit.B1) level was also determined. Overall nutritional status was significantly inferior to the control Japanese inhabitants, even after a certain period of custody, including vit.B1 level. As for mineral levels, Mg, Fe, and P concentrations in the blood of people in Kyoto Detention House were significantly low compared to those of control Japanese inhabitants, even though these tendencies were somewhat improved in custody. 

Key words: nutrition, detention, minerals 

Magnesium and other mineral levels in the blood of middle age Japanese men and women

R. Takeda¹, T. Suyama², Y. Minakuchi², M. Ishida¹, M. Imanishi¹, H. Shigetomi¹, A. Takeda¹, T. Takeda¹, R. Kitamura², M. Kimura¹  

¹ Takeda Research Institute of Life Science; 
² Takeda Hospital Health Center 

To clarify mineral nutritional status, 421 men (46.2 ± 8.2 years) and 277 women (45.7 ± 8.7 years), total 698 inhabitants living in Kyoto and Shiga Prefectures in Japan, were selected as volunteers with informed consent. Magnesium(Mg), calcium(Ca), sulfur(S), Iron(Fe), phosphorus(P), zinc(Zn) and copper(Cu) concentrations in blood were determined by inductively coupled plasma-atomic emission spectrometry (OPTIMA4300DV: Perking-Elmer Co. Ltd., USA) in blood after wet digestion by nitric acid. They were healthy subjects (having no disease). Blood mineral levels were as follows (average ± SD); Mg(μg/mL): 37.4 ± 3.2, Ca(μg/mL): 57.9 ± 3.8, S(mg/mL): 1.55 ± 0.12, Fe(μg/mL): 519 ± 38.6, P(μg/mL): 393 ± 32.6, Zn(μg/mL): 6.66 ± 0.78, Cu(ng/mL): 778 ± 91.8 in men and Mg(μg/mL): 34.7 ± 3.2, Ca(μg/mL): 62.5 ± 3.8, S(mg/mL): 1.47 ± 0.11, Fe(μg/mL): 443 ± 46.5, P(μg/mL): 368 ± 30.9, Zn(μg/mL): 5.86 ± 0.75, Cu(ng/mL): 838 ± 91.8 in women. Mg, S, Fe, P and Zn concentrations in blood of men were significantly high compared to that of women, and Ca and Cu concentrations in men were low compared to those of women. 

Key words: mineral levels in blood, healthy subjects, men, women 

The relation of birth weight to intracellular magnesium of cord-blood platelets

Junji Takaya, Fumiko Yamato, Hirohiko Higashino, Yohnosuke Kobayashi 

Department of Pediatrics, Kansai Medical University 

Objective. Magnesium has an important role in insulin action, and insulin stimulates magnesium uptake in insulin-sensitive tissues. Impaired biological responses to insulin are referred to as insulin resistance. Diabetic patients and obese subjects are reported to have intracellular magnesium ([Mg²⁺]ⁱ) deficiency. Many epidemiological studies have disclosed that restricted fetal growth has been associated with an increased risk of insulin resistance in the adult life. We studied the relationship of [Mg²⁺]_i in cord blood platelets to birth weight. 
Methods. The subjects were 19 infants who were small for gestational age (SGA) and 45 who were appropriate for gestational age (AGA). By using a fluorescent probe, mag-fura-2, we examined the basal and insulin-stimulated [Mg²⁺]ⁱ of platelets in the cord blood. Cord plasma IGF-1and leptin levels were determined with the use of ELISA. 
Results. Birth weight was correlated with cord plasma IGF-1 (p < 0.001) and leptin (p < 0.005). Mean basal [Mg²⁺]_i, but not plasma magnesium, was lower in the SGA than in the AGA group (291 ± 149 mmol/L vs 468 ± 132 mmol/L, p < 0.001). The basal [Mg²⁺]_i was significantly correlated with the birth weight (p < 0.001) as well as birth length (p < 0.001). At 60 seconds after stimulation with insulin, there was no significant difference in stimulated [Mg²⁺]_i between the SGA and AGA groups. Although the SGA group had low [Mg²⁺]_i, the platelets has good potentiality to compensate for low [Mg²⁺]_i. 
Conclusions. [Mg²⁺]_i reflects the extent of fetal growth. Decreased [Mg²⁺]_i in SGA might underlie the initial pathophysiologic events leading to insulin resistance.

Key words: Mg in platelets, cord blood, birth weight 

Positive correlation between dietary sodium intake and balances of calcium and magnesium in humans

Mamoru Nishimuta¹, Naoko Kodama^{1, 2}, Eiko Morikuni¹, Nobue Matuzaki¹, Yayoi H. Yoshioka¹, Hidemaro Takeyama^{1, 3}, Hideaki Yamada^{1, 4}, Hideaki Kitajima^{1, 5}  

¹ The Incorporated Administrative Agency of Health and Nutrition; 
² Medical University of Yamanashi and Tokyo College of Nutrition and Food; 
³ Nagoya City University Graduate School of Medical Science; 
⁴ Mimasaka Women's University; 
⁵ Taisho Pharmaceutical Co. Ltd 

The purpose of this study is to investigate the relation between sodium (Na) intake and balances of calcium (Ca) and magnesium (Mg). From 1986 to 2000 11 mineral balance studies were carried out with 109 volunteers, using foodstuffs available in the market. In all cases, Na intake was positively correlated with Na balance. However this correlation disappeared after data at the highest sodium intake was removed. In all cases, Na intake was not correlated with the balances of Ca nor Mg. However Na intake was positively correlated with the balances of Ca and Mg after removing data at the highest sodium intake study. After omitting the data of the highest and lowest Na intake, intakes of Ca and Mg were positively correlated with the balances of respective minerals. 

Key words: mineral balances, correlation 

Correlation between magnesium levels and congestive heart failure in children

Kenji Hoshino, Kiyoshi Ogawa, Takashi Hishitani, Tatsuya Ando, Youichirou Hirata, Youko Kawai 

Pediatric Cardiology, Saitama Children’s Medical Center 

We measured total and ionized magnesium levels and urine magnesium excretion (FEMg) in children with congestive heart failure (CHF). Serum ANP and BNP levels were also measured as an indicate of CHF, and we evaluated the correlation between them. 
There was no significant correlation between ANP & BNP levels and magnesium levels. Magnesium levels were not significantly different between the normal ANP group and the high ANP group. Magnesium levels, except FEMg, were not significantly different between the normal BNP group and the high BNP group. FEMg was significantly higher in the normal ANP group than in the high BNP group (7.1 ± 9.4 pg/mL: 3.6 ± 3.4 pg/mL, p = 0.019).
Hypomagnesemia was not recognized in children with CHF, and the lower magnesium excretion was found in the high BNP group, showing the magnesium-sparing in these children. 

Key words: heart failure, children, BNP 

Effects of serum magnesium on refractory hyperparathyroidism of uremia

Yoshihiro Tsujimoto¹, Hideki Tahara², Tsutomu Tabata¹, Takashi Inoue¹, Masaaki Inaba² and Yoshiki Nishizawa² 

¹ Inoue Hospital; 
² Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine 

We evaluated the effects of serum magnesium on the progression of refractory hyperparathyroidism. We studied 107 patients who underwent parathyroidecomy for refractory hyperparathyroidism due to chronic renal failure. The levels of serum intact PTH were negatively correlated with the levels of magnesium. To estimate the contribution of the value of each clinical parameter to the level of intact PTH, multiple regression analysis was performed. As a result, levels of serum magnesium and the total weight of resected parathyroids were demonstrated to be significant independent factors. 

Key words: serum MG, hyperparathyroidism, uremia 

Relationship between serum magnesium and vascular calcification in hemodialysis patients

Senji Okuno, Eiji Ishimura, Yoshifumi Maeno, Yoko Fujino, Tomoyuki Yamakawa, Masaaki Inaba, Yoshiki Nishizawa 

Shirasagi Hospital, Department of Nephrology and Department of metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine 

Although vascular calcification is frequently seen in uremic patients, contributing factors to vascular calcification (VC) are not fully clarified. We examined the roentgenological appearance of VC of the hand in 385 non-diabetic hemodialysis (HD) patients. Prevalence of VC was significantly higher in males than in females. Serum P, Ca x P product and intact PTH were significantly higher and HD duration was significantly longer in patients with VC than in patients without VC. Age was higher and serum Mg was lower in patients with VC than in patients without VC, although these differences did not reach statistical significance. In logistic regression analysis, male gender, older age, longer HD duration, higher Ca x P product and lower Mg were the variables significantly associated with the presence of VC. These results demonstrate that VC in end-stage renal disease is affected by gender, HD duration and altered Ca EP metabolism. Our results also suggest that higher levels of Mg may prevent the development of VC in HD patients. 

Key words: vascular calcification, hemodialysis, serum Mg 

The relationships between markers of either bone resorption or bone formation and serum magnesium or calcium levels

Noburu Saito¹, Saburou Saito¹, Yoshihisa Andou², Naoto Tabata² 

¹ Internal medicine and Center for Lifestyle-related Diseases, Miyazaki Medical Center Hospital; 
² Center for Alimentary tract and Liver Diseases, Miyazaki Medical Center Hospital 

The aim of this study is to clarify the relationships between markers of either bone resorption or bone formation and serum magnesium or calcium levels in elderly inpatients. 
In this study 81 female inpatients were recruited, who did not take furosemide and had less than 30 mg/dL of BUN, to exclude renal failure. 
Of these inpatients, 50 did not take MgO and the remaining 31 took MgO as a laxative. 
Markers of bone resorption such as urinary Dpd and NTx were measured, they were obtained early in the morning. Fasting blood samples were obtained early in the morning. Serum magnesium was measured with colorimetry. Serum calcium and ionized calcium were measured. 
In high normal range of serum magnesium, urinary Dpd/cr tended to decrease, suggesting the relationship between urinary Dpd and serum magnesium levels. 

Key words: bone resorption, bone formation, serum Mg, serum Ca

Effect of magnesium on neural activities in vitro

Keiichi Torimitsu, Nahoko Kasai and Yuriko Furukawa 

NTT Basic Research Laboratories, SORST/JST 

Magnesium is well known to play an important role in biological functions, especially in neural activities. However, little is known about the functional role of magnesium on neural activities. We investigated the Mg2+ effect on electrical activities and synaptic glutamate release by using Micro-Electrode Array (MEA) and Enzyme modified MEA sensor (EMEA). NDMA receptor involvement will be discussed. 

Key words: nervous system, Mg, Micro-Electrode Array (MEA)