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Clinical Studies on the use and effects of Ionized Alkaline (Reduced) Water

Chlorination Studies

Pain: A paradigm change

A. Ionized Alkaline (Reduced) Water Study Abstracts

1. Influences of alkaline ionized water on milk yield, body weight of offspring and perinatal dam in rats.

2. Histopathological influence of alkaline ionized water on myocardial muscle of mother rats.

3. Degradation of myocardiac myosin and creatine kinase in rats given alkaline ionized water.

4. Influence of alkaline ionized water on rat erythrocyte hexokinase activity and myocardium.

5. Effect of alkaline ionized water on reproduction in gestational and lactational rats.

6. Impact of extra waters on immunosystem in mice

7. Selective stimulation of the growth of anaerobic microflora in the human intestinal tract by electrolyzed reducing water.

8. Water desirable for health in terms of ORP (oxidation-reduction potential) to pH relationship

9. Influences of alkaline ionized water on milk electrolyte concentrations in maternal rats.

10. Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage.

11. The mechanism of the enhanced antioxidant effects against superoxide anion radicals of reduced water produced by electrolysis.

12. Protective mechanism of reduced water against alloxan-induced pancreatic beta-cell damage: Scavenging effect against reactive oxygen species

13. Electrolyzed hydrogen-saturated water for drinking use elicits an antioxidative effect: a feeding test with rats.

14. Effects of supplementing of calcium, iron and zinc on women's health during pregnancy (not about ionized water)

15. Supplementation with alkaline minerals reduces symptoms in patients with chronic low back pain (not about ionized water)

 

B. Clinical Study Reports on Alkaline Reduced) Water

1. Physiological effects of alkaline ionized water: Effects on metabolites produced by intestinal fermentation

2. Clinical evaluation of alkaline ionized water for abdominal complaints: Placebo controlled double blind tests

3. Effect of Electrolytic Water (Ionized Water) Intake on Lifespan of Autoimmune Disease Prone Mice

4.Effects on metabolites produced by intestinal fermentation

5. Reduced Water for Prevention of Diseases

6. Clinical Impovements Obtained From The Intake Of Reduced Water

7. Effects of alkaline ionized water on formation & maintenance of osseous tissues

 

C. Clinical Studies on the effects of Oxidized/Acid Ionized Water

 

D. Drinking Water Chlorination Studies

  1. References
  2. Recent epidemiological studies
  3. Recent papers on exposure and uptake
  4. Recent studies in laboratory animals
  5. Recent review papers

E. Pain: a paradigm change

 

F. Pharmaceutical drugs and Personal Care Pollutants in water

1. Emerging chemicals of concern: pharmaceuticals and personal care products (PPCPs) in Asia, with particular reference to Southern China

2. Occurrence and fate of pharmaceuticals and personal care products (PPCPs) in biosolids

3. Occurrence of pharmaceutical contaminants and screening of treatment alternatives for southeastern Louisiana

4. Ecotoxicology of human pharmaceuticals

 

 

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A. Ionized Alkaline (Reduced) Water Study Abstracts

 

1. Influences of alkaline ionized water on milk yield, body weight of offspring and perinatal dam in rats.

J Toxicol Sci. 1998 Dec;23(5):365-71. Watanabe T , Pan I , Fukuda Y , Murasugi E , Kamata H , Uwatoko K .

Department of Veterinary Physiological Chemistry, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.

The authors previously reported that male offspring of mothers rats given alkaline ionized water (AKW) showed a significantly higher body weight by day 14 after birth than did offspring of mother rats given tap water (TPW); furthermore, marked myocardial necrosis and fibrosis were observed particularly in the former male offspring at the age of 15 weeks. In the present experiment we looked for differences in bioparameters, namely the milk yield of mothers and suckled milk volume of the offspring, between the AKW- and the TPW-treated groups in order to reveal the factors which cause the unusual body weight gain in the offspring. Even though we were able to repeat our previous observation (the body weight of the male offspring of the AKW group increased significantly more by day 14 and 20 after birth and of the female by day 20 after birth than did that of the TPW group (p < 0.05), no significant difference was noted in any of the bioparameters, including those related to milk production and consumption. It is thus suspected that the water-hydrated cation, which was transferred either to the fetus through the placenta or to the offspring through the milk, might be the cause of the unusual body weight increase. Since calcium plays an important role in skeletal formation, it is tentatively concluded that the higher calcium concentration of AKW enriched the mother, serum calcium which was transferred to the fetus through the placenta and to the offspring through the milk.

PMID: 9922938 [PubMed - indexed for MEDLINE]

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2. Histopathological influence of alkaline ionized water on myocardial muscle of mother rats.

J Toxicol Sci. 1998 Dec;23(5):411-7. Watanabe T , Shirai W , Pan I , Fukuda Y , Murasugi E , Sato T , Kamata H , Uwatoko K .

Department of Veterinary Physiological Chemistry, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.

We have reported that a marked necrosis and subsequent fibrosis of myocardium occurred among male rats 15 weeks old given alkaline ionized water (AKW) during gestation and suckling periods, and after weaning. In this study, it was examined whether similar lesions would occur in mother rats which were given AKW from day zero of gestation to day 20 of lactation. The myocardial lesion in the mother rats given AKW showed cell infiltration, vacuolation and fibrosis in the papillary muscle of the left ventricle, as were observed in male rats of 15 weeks old. Myocardial degeneration may cause a leakage of potassium into the blood that results in a higher concentration of potassium in the blood in the test group than in that of the control group given tap water.

PMID: 9922944 [PubMed - indexed for MEDLINE]

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3. Degradation of myocardiac myosin and creatine kinase in rats given alkaline ionized water.

J Vet Med Sci. 1998 Feb;60(2):245-50. Watanabe T , Kishikawa Y .

Department of Veterinary Physiological Chemistry, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.

Recently, the authors have shown that marked necrosis and fibrosis of myocardium were observed in rats given alkaline ionized water (AKW). To clarify the cause of myocardial lesions, the activities of myosin ATPase, actomyosin ATPase and creatine kinase (CK) in myocardium of rats given AKW at 15 weeks-old were compared with those in myocardium of rats given tap water (TPW). Furthermore, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of myocardiac myosin and isoelectric focusing (IEF) of myocardiac CK were performed which revealed a distinct difference between AKW and TPW groups. The activities of myosin ATPase and actomyosin ATPase in the AKW group were higher than those in the TPW group, and these elevated activities were caused by the degradation of myosin in the AKW group judging from the SDS-PAGE pattern of myosin. On the other hand, the activity of CK in the AKW group was lower than that in the TPW group, and the IEF pattern of CK showed leakage of myocardiac CK. These results indicate that increases in actomyosin ATPase activity and myosin ATPase activity, plus the decrease in CK activity caused the disorder of coupled reaction in male rats given AKW at 15 weeks-old. It is concluded that this disorder of coupled reaction may cause marked myocardiac necrosis and fibrosis in rats given AKW.

PMID: 9524951 [PubMed - indexed for MEDLINE]

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4. Influence of alkaline ionized water on rat erythrocyte hexokinase activity and myocardium.

J Toxicol Sci. 1997 May;22(2):141-52. Watanabe T , Kishikawa Y , Shirai W .

Department of Veterinary Physiological Chemistry, College of Bioresource Science, Nihon University, Kanagawa, Japan.

Alkaline ionized water (AKW) produced by the electrolysis of tap water (TPW) was given to pregnant rats throughout gestation. AKW was subsequently given to infants as a test group until 15 weeks old to determine changes in body and organ weights, erythrocyte hexokinase (HK) activity and histological preparations of myocardiac muscle. The results were compared with those for rats given TPW. Body weight of male and female rats given AKWA at 3 to 11 weeks of age after birth significantly increased beyond control group values. Organ weights of offspring at 15 weeks-old showed no statistical difference for either group. HK activity, the rate-determining enzyme in erythrocyte glycolysis, significantly increased in males given AKW at 15 weeks-old. This suggests that AKW intake causes elevation of metabolic activity. Hyperkalemia was observed in males and females given AKW at 15 weeks-old. Especially in males, pathological changes of necrosis in myocardiac muscle were observed.

PMID: 9198011 [PubMed - indexed for MEDLINE]

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5. Effect of alkaline ionized water on reproduction in gestational and lactational rats.

J Toxicol Sci. 1995 May;20(2):135-42. Watanabe T .

Department of Veterinary Physiological Chemistry, College of Agriculture and Veterinary Medicine, Nihon University, Kanagawa, Japan.

Alkaline ionized water (AKW) produced by electrolysis was given to gestational and lactational rats, and its effect on dams, growth of fetuses and offsprings were investigated. The results showed that the intake of food and water in dams increased significantly when AKW was given from the latter half of the gestation period and from the former half of the lactation period. Body weight of the offsprings in the test group, both males and females, increased significantly from the latter half of the lactation period. During the lactation period and after weaning, the offsprings in the test group showed significantly hastened appearance of abdominal hair, eruption of upper incisors, opening of eyelids and other postnatal morphological developments both in males and females, as well as earlier separation of auricle and descent of testes in males compared with the control was noted. As mentioned above, it was suggested from the observations conducted that the AKW has substantial biological effects on postnatal growth, since intake of food and water and body weight of the offsprings increased and postnatal morphological development was also accelerated.

PMID: 7473891 [PubMed - indexed for MEDLINE]

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6. Impact of extra waters on immunosystem in mice

Wei Sheng Yan Jiu. 2004 Jul;33(4):422-5. [Article in Chinese]

Li Y , Han C , Li Y , Li Y , Zhao X , Zhong K , Chen T , Zhang M , Fan F , Tao Y , Ji R .

Institute of Nutrition and Food Safety, Chinese Center for Disease Control and Prevention, Beijing 100021, China.

OBJECTIVE: To study impact of extra waters on immunosystem in mice-alkaline ionized water, mineralecology water, activated water, and pure water. METHODS: According to Function Assessment and Experiment for Function Food, 1996, the ratio of spain and body weight, the ratio of thymus and body weight, the delayed type hypersensitivity (DTH), the phagocytosing functions by cock RBC, the plaque forming cell (PFC) and HC50 testing were assessment with 120 male Balb/c mice of 17.8 - 23.3 g (group I), the mice were divided into four group, and drank daily the four kinds of waters respectively until 50 days. The lymph cell transformation by ConA and NK cell activity were assessment with otherl20 male Balb/c mice of 17.8 - 23.3 g (group II), the mice were divided into four group and drank daily the four kinds of waters respectively until 50 days. The phagocytosing functions by carbon powder were assessment with other 120 female Balb/c mice of 16.7 - 22.0 g (group III) were divided into four group and drank daily the four kinds of waters respectively until 50 days. The data were statisticed by Stata soft. RESULTS: Other three waters compared with the pure water: (1) Alkaline ionized water and activated water can alleviate the body weight increase of male Balb/c mouse (P < 0.01 & P < 0.05), but alkaline ionized water, mineral-ecology water, activated water don't impact on the female Balb/c mouse body weight (P > 0.05). (2) Activated water can remarkly increase the ratio of thymus and body weight (P < 0.05), and increase the phagocytosing ability by cock RBC (P < 0.01), and increase the NK cell activity (P < 0.01). (3) The three extra waters don't impact on othe items for the Balh/c mouce. CONCLUSION: The study must be continued to impact on immunosystem in mice for extra waters.

PMID: 15461264 [PubMed - in process]

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7. Selective stimulation of the growth of anaerobic microflora in the human intestinal tract by electrolyzed reducing water.

Med Hypotheses. 2005;64(3):543-6. Vorobjeva NV .

Department of Physiology of Microorganisms, Biology Faculty, Lomonosov Moscow State University, 119992 Moscow, Russia. nvvorobjeva@mail.ru 96-99% of the "friendly" or residential microflora of intestinal tract of humans consists of strict anaerobes and only 1-4% of aerobes. Many diseases of the intestine are due to a disturbance in the balance of the microorganisms inhabiting the gut. The treatment of such diseases involves the restoration of the quantity and/or balance of residential microflora in the intestinal tract. It is known that aerobes and anaerobes grow at different oxidation-reduction potentials (ORP). The former require positive E(h) values up to +400 mV. Anaerobes do not grow unless the E(h) value is negative between -300 and -400 mV. In this work, it is suggested that prerequisite for the recovery and maintenance of obligatory anaerobic microflora in the intestinal tract is a negative ORP value of the intestinal milieu. Electrolyzed reducing water with E(h) values between 0 and -300 mV produced in electrolysis devices possesses this property. Drinking such water favours the growth of residential microflora in the gut. A sufficient array of data confirms this idea. However, most researchers explain the mechanism of its action by an antioxidant properties destined to detox the oxidants in the gut and other host tissues. Evidence is presented in favour of the hypothesis that the primary target for electrolyzed reducing water is the residential microflora in the gut.

PMID: 15617863 [PubMed - indexed for MEDLINE]

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8. Water desirable for health in terms of ORP (oxidation-reduction potential) to pH relationship

Review
PMID: 2829704 [PubMed - indexed for MEDLINE]

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9. Influences of alkaline ionized water on milk electrolyte concentrations in maternal rats.

J Toxicol Sci. 2000 Dec;25(5):417-22. Watanabe T , Kamata H , Fukuda Y , Murasugi E , Sato T , Uwatoko K , Pan IJ .

Department of Veterinary Biochemistry, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-8510, Japan.

We previously reported that body weight on day 14 after birth in male offspring of rats given alkaline ionized water (AKW) was significantly heavier than that in offspring of rats given tap water (TPW), but no significant difference was noted in milk yield and in suckled milk volume between the two groups. Additionally, the offspring in the AKW group and TPW group were given AKW and TPW, respectively, at weaning, and unexpectedly, the necrotic foci in the cardiac muscle were observed at the 15-week-old age in the AKW group, but not in the TPW group. The present study was designed to clarify the factors which are involved in that unusual increase of body weight and occurrence of cardiac necrosis. Eight dams in each group were given AKW or TPW (control) from day 0 of gestation to day 14 of lactation. The milk samples were collected on day 14 of lactation and analyzed for concentrations of calcium (Ca), sodium (Na), potassium (K), magnesium (Mg) and chloride (Cl). The AKW and TPW were also analyzed. Ca, Na and K levels in milk were significantly higher in the AKW group compared to the TPW group. No significant difference was noted in the Mg and Cl levels between the two groups. These data suggested that the Ca cation of AKW enriched the Ca concentration of the milk and accelerated the postnatal growth of the offspring of rats given AKW.

PMID: 11201172 [PubMed - indexed for MEDLINE]

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10. Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage.

Biochem Biophys Res Commun. 1997 May 8;234(1):269-74.

Shirahata S , Kabayama S , Nakano M , Miura T , Kusumoto K , Gotoh M , Hayashi H , Otsubo K , Morisawa S , Katakura Y .

Institute of Cellular Regulation Technology, Graduate School of Genetic Resources Technology, Kyushu University, Fukuoka, Japan. sirahata@grt.kyushu-u.ac.jp

Active oxygen species or free radicals are considered to cause extensive oxidative damage to biological macromolecules, which brings about a variety of diseases as well as aging. The ideal scavenger for active oxygen should be 'active hydrogen'. 'Active hydrogen' can be produced in reduced water near the cathode during electrolysis of water. Reduced water exhibits high pH, low dissolved oxygen (DO), extremely high dissolved molecular hydrogen (DH), and extremely negative redox potential (RP) values. Strongly electrolyzed-reduced water, as well as ascorbic acid, (+)-catechin and tannic acid, completely scavenged O.-2 produced by the hypoxanthine-xanthine oxidase (HX-XOD) system in sodium phosphate buffer (pH 7.0). The superoxide dismutase (SOD)-like activity of reduced water is stable at 4 degrees C for over a month and was not lost even after neutralization, repeated freezing and melting, deflation with sonication, vigorous mixing, boiling, repeated filtration, or closed autoclaving, but was lost by opened autoclaving or by closed autoclaving in the presence of tungsten trioxide which efficiently adsorbs active atomic hydrogen. Water bubbled with hydrogen gas exhibited low DO, extremely high DH and extremely low RP values, as does reduced water, but it has no SOD-like activity. These results suggest that the SOD-like activity of reduced water is not due to the dissolved molecular hydrogen but due to the dissolved atomic hydrogen (active hydrogen). Although SOD accumulated H2O2 when added to the HX-XOD system, reduced water decreased the amount of H2O2 produced by XOD. Reduced water, as well as catalase and ascorbic acid, could directly scavenge H2O2. Reduce water suppresses single-strand breakage of DNA b active oxygen species produced by the Cu(II)-catalyzed oxidation of ascorbic acid in a dose-dependent manner, suggesting that reduced water can scavenge not only O2.- and H2O2, but also 1O2 and .OH.

PMID: 9169001 [PubMed - indexed for MEDLINE]

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11. The mechanism of the enhanced antioxidant effects against superoxide anion radicals of reduced water produced by electrolysis.

Biophys Chem. 2004 Jan 1;107(1):71-82.

Hanaoka K , Sun D , Lawrence R , Kamitani Y , Fernandes G .
Bio-REDOX Laboratory Inc. 1187-4, Oaza-Ueda, Ueda-shi, Nagano-ken 386-0001, Japan. hanak@rapid.ocn.ne.jp
We reported that reduced water produced by electrolysis enhanced the antioxidant effects of proton donors such as ascorbic acid (AsA) in a previous paper. We also demonstrated that reduced water produced by electrolysis of 2 mM NaCl solutions did not show antioxidant effects by itself. We reasoned that the enhancement of antioxidant effects may be due to the increase of the ionic product of water as solvent. The ionic product of water (pKw) was estimated by measurements of pH and by a neutralization titration method. As an indicator of oxidative damage, Reactive Oxygen Species- (ROS) mediated DNA strand breaks were measured by the conversion of supercoiled phiX-174 RF I double-strand DNA to open and linear forms. Reduced water had a tendency to suppress single-strand breakage of DNA induced by reactive oxygen species produced by H2O2/Cu (II) and HQ/Cu (II) systems. The enhancement of superoxide anion radical dismutation activity can be explained by changes in the ionic product of water in the reduced water.

PMID: 14871602 [PubMed - indexed for MEDLINE]

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12. Protective mechanism of reduced water against alloxan-induced pancreatic beta-cell damage: Scavenging effect against reactive oxygen species

Authors: Li Y.1; Nishimura T.1; Teruya K.1; Maki T.1; Komatsu T.1; Hamasaki T.1; Kashiwagi T.1; Kabayama S.2; Shim S-Y.1; Katakura Y.1; Osada K.1; Kawahara T.1; Otsubo K.2; Morisawa S.2; Ishii Y.3; Gadek Z.4; Shirahata S.5

Source: Cytotechnology, Volume 40, Numbers 1-3, 2002, pp. 139-149(11)
Publisher: Springer

Abstract:

Reactive oxygen species (ROS) cause irreversible damage to biological macromolecules, resulting in many diseases. Reduced water (RW) such as hydrogen-rich electrolyzed reduced water and natural reduced waters like Hita Tenryosui water in Japan and Nordenau water in Germany that are known to improve various diseases, could protect a hamster pancreatic beta cell line, HIT-T15 from alloxan-induced cell damage. Alloxan, a diabetogenic compound, is used to induce type 1 diabetes mellitus in animals. Its diabetogenic effect is exerted via the production of ROS. Alloxan-treated HIT-T15 cells exhibited lowered viability, increased intracellular ROS levels, elevated cytosolic free Ca2+ concentration, DNA fragmentation, decreased intracellular ATP levels and lowering of glucose-stimulated release of insulin. RW completely prevented the generation of alloxan-induced ROS, increase of cytosolic Ca2+ concentration, decrease of intracellular ATP level, and lowering of glucose-stimulated insulin release, and strongly blocked DNA fragmentation, partially suppressing the lowering of viability of alloxan-treated cells. Intracellular ATP levels and glucose-stimulated insulin secretion were increased by RW to 2–3.5 times and 2–4 times, respectively, suggesting that RW enhances the glucose-sensitivity and glucose response of beta-cells. The protective activity of RW was stable at 4 °C for over a month, but was lost by autoclaving. These results suggest that RW protects pancreatic beta-cells from alloxan-induced cell damage by preventing alloxan-derived ROS generation. RW may be useful in preventing alloxan-induced type 1-diabetes mellitus.

Affiliations: 1: Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, Japan 2: Nihon Trim Co. Ltd., 1-8-34 Oyodonaka, Kita-ku, Osaka, Japan 3: Hita Tenryosui Co. Ltd., 647 Nakanoshima, Hita, Oita, Japan 4: Center for Holistic Medicine and Naturopathy, Schmallenberg-Nordenau, Germany 5: Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, Japan (Author for correspondence; E-mail: sirahata@grt.kyushu-u.ac.jp; Fax: +81 92 642 3052)

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13. Electrolyzed hydrogen-saturated water for drinking use elicits an antioxidative effect: a feeding test with rats.


Biosci Biotechnol Biochem. 2005 Oct;69(10):1985-7

Yanagihara T, Arai K, Miyamae K, Sato B, Shudo T, Yamada M, Aoyama M.

MiZ Co., Ltd., Fujisawa-shi, Kanagawa, Japan.

A new type of electrolyzed hydrogen-saturated (EHS) water was produced using a water-electrolyzing device equipped with a special cation exchanger. Use of the EHS water for drinking in a feeding test with rats elicited an antioxidative effect. After intraperitoneal injection of 2,2-azobis-amidinopropane dihydrochloride, urinary secretion of 8-hydroxydeoxyguanosine and hepatic formation of peroxidized lipid were significantly lessened in rats which had received the EHS water for one week. These results suggest the possibility that this drinking water shows an effect in reduction of oxidative stress in the body.

PMID: 16244454 [PubMed - in process]

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[Editors note: following two studies are not about ionized water, but about effects of increrasing alkaline minerals JK]

14. Effects of supplementing of calcium, iron and zinc on women's health during pregnancy

Zhonghua Yu Fang Yi Xue Za Zhi. 2001 Nov;35(6):365-9. [Article in Chinese]

An H, Yin S, Xu Q.

Department of Maternal and Child Nutrition, Institute of Nutrition and Food Hygiene, Chinese Academy of Preventive Medicine, Beijing 100050, China.

OBJECTIVES: To determine the effects of supplementing biscuits fortified with calcium (Ca) and vitamin D (VD), iron (Fe), vitamin C (VC) and zinc (Zn) to pregnant women from the 5th month of gestation until delivery on their health, and to explore a way to improve their Ca, Fe and Zn nutritional status during pregnancy. METHODS: A total of 313 healthy and primary pregnant women were enrolled and divided into five study groups based on their order visiting the hospitals for prenatal care. Each woman of the study groups was given three pieces of biscuit fortified with VD, Ca and VD, Ca, Zn and VD (Ca + Zn + VD), Ca, Fe, VC and VD (Ca + Fe + VD), Ca, Fe, VC, Zn and VD (Ca + Fe + Zn + VD), respectively, from the 15th month of gestation until delivery (24 weeks in total) daily. The fortified levels were 10 micrograms VD, 400 mg Ca from carbonate calcium, 10 mg Zn from lactate zinc, 10 mg Fe from ferrous lactate, and 50 mg VC, respectively. A parturient women was selected from the same hospital as control after one trial subject for each study groups selected. RESULTS: The daily dietary intakes of Ca, Zn and Fe in pregnant women were only 47.7%, 54.7% and 86.7% of the Recommended Dietary Allowances for Chinese. Incidence of anemia for mid-term pregnant women was 35.2%, and Fe-supplementation could significantly improved their hemoglobin level (P < 0.05). Prevalence of anemia in the groups of Ca + Fe + Zn + VD and Ca + Fe + VD was 35.3% and 40.7%, respectively, before Fe supplementation and reduced to zero and 4.0%, respectively, after Fe supplementation. Whereas, prevalence of anemia in the other groups without Fe supplementation still kept in a relatively high level. In the groups supplemented with Ca, their plasma Ca level increased, especially with the best results in Ca + VD group. Plasma level of Zn declined with length of gestation, which could be improved by Zn supplementation. Serum level of alkaline phosphatase activity increased a little bit with length of gestation. There was no significant difference in radial and ulnar bone mineral density (BMD) between trial groups and controls two months after delivery. Maternal radial and ulnar BMD correlated significantly with their dietary Ca intakes in Ca + VD group. CONCLUSION: The best way to improve maternal nutritional status is supplementation of Ca + Fe + Zn + VitD, based on the Recommended Dietary Allowances for Chinese.

PMID: 11840760 [PubMed - indexed for MEDLINE]

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15. Supplementation with alkaline minerals reduces symptoms in patients with chronic low back pain.

1: J Trace Elem Med Biol. 2001;15(2-3):179-83.

Vormann J, Worlitschek M, Goedecke T, Silver B.

Institut fur Pravention und Ernahrung, Ismaning, Germany. vormann@ipev.de

The cause of low back pain is heterogeneous, it has been hypothesised that a latent chronic acidosis might contribute to these symptoms. It was tested whether a supplementation with alkaline minerals would influence symptoms in patients with low back pain symptoms. In an open prospective study 82 patients with chronic low back pain received daily 30 g of a lactose based alkaline multimineral supplement (Basica) over a period of 4 weeks in addition to their usual medication. Pain symptoms were quantified with the "Arhus low back pain rating scale" (ARS). Mean ARS dropped highly significant by 49% from 41 to 21 points after 4 weeks supplemention. In 76 out of 82 patients a reduction in ARS was achieved by the supplementation. Total blood buffering capacity was significantly increased from 77.69 +/- 6.79 to 80.16 +/- 5.24 mmol/L (mean +/- SEM, n = 82, p < 0.001) and also blood pH rose from 7.456 +/- 0.007 to 7.470 +/- 0.007 (mean +/- SEM, n = 75, p < 0.05). Only intracellular magnesium increased by 11% while other intracellular minerals were not significantly changed in sublingual tissue as measured with the EXA-test. Plasma concentrations of potassium, calcium, iron, copper, and zinc were within the normal range and not significantly influenced by the supplementation. Plasma magnesium was slightly reduced after the supplemenation (-3%, p < 0.05). The results show that a disturbed acid-base balance may contribute to the symptoms of low back pain. The simple and safe addition of an alkaline multimineral preparate was able to reduce the pain symptoms in these patients with chronic low back pain.

Publication Types:

* Clinical Trial

PMID: 11787986 [PubMed - indexed for MEDLINE]

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B . CLINICAL STUDIES Reports on Alkaline (reduced) water
1. Physiological effects of alkaline ionized water: Effects on metabolites produced by intestinal fermentation
2. Clinical evaluation of alkaline ionized water for abdominal complaints: Placebo controlled double blind tests
3. Effect of Electrolytic Water (Ionized Water) Intake on Lifespan of Autoimmune Disease Prone Mice
4.Effects on metabolites produced by intestinal fermentation
5. Reduced Water for Prevention of Diseases
6. Clinical Impovements Obtained From The Intake Of Reduced Water

1. Physiological effects of alkaline ionized water: Effects on metabolites produced by intestinal fermentation

Takashi Hayakawa, Chicko Tushiya, Hisanori Onoda, Hisayo Ohkouchi, Haruto Tsuge (Gifu University, Faculty of Engineering, Dept. of Food Science)

"We have found that long-term ingestion of alkaline ionized water (AIW) reduces cecal fermentation in rats that were given highly fermentable commercial diet (MF: Oriental Yeast Co., Ltd.). In this experiment, rats were fed MF and test water (tap water, AIW with pH at 9 and 10) for about 3 months. Feces were collected on the 57th day, and the rats were dissected on the 88th day. The amount of ammonium in fresh feces and cecal contents as well as fecal free-glucose tended to drop down for the AIW group. In most cases, the amount of free-amino acids in cecal contents did not differ sign- icantly except for cysteine (decreased in AIW with pH at 10) and isoleucine (increased in AIW with pH at 10).

Purpose of tests

Alkaline ionized water electrolyzers have been approved for manufacturing in 1965 by the Ministry of Health and Welfare as medical equipment to produce medical substances. Alkaline ionized water (AIW) produced by this equipment is known to be effective against gastrointestinal fermentation, chronic diarrhea, indigestion and hyperchylia as well as for controlling gastric acid.

1. This is mainly based on efficacy of the official calcium hydroxide.
2. By giving AIW to rats for a comparatively long time under the condition of extremely high level of intestinal fermentation, we have demonstrated that AIW intake is effective for inhibition of intestinal fermentation when its level is high based on some test results where AIW worked against cecal hypertrophy and for reduction in the amount of short-chain fatty acid that is the main product of fermentation.
3. We have reported that this is caused by the synergy between calcium level generally contained in AIW (about 50ppm) and the value of pH, and that frequency of detecting some anaerobic bacteria tends to be higher in alkaline ionized water groups than the other, although the bacteria count in the intestine does not have significant difference. Based on these results, we made a judgment that effect of taking AIW supports part of inhibition mechanism against abnormal intestinal fermentation, which is one of the claims of efficacy that have been attributed to alkaline ionized water electrolyzers.
4. On the other hand, under the dietary condition of low intestinal fermentation, AIW uptake does not seem to inhibit fermentation that leads us to believe that effect of AIW uptake is characteristic of hyper-fermentation state. Metabolites produced by intestinal fermentation include indole and skatole in addition to organic acids such as short-chain fatty acid and lactic acid as well as toxic metabolites such as ammonium, phenol and pcresol. We do not know how AIW uptake would affect the production of these materials. In this experiment, we have tested on ammonium production as explained in the following sections.

Testing methods

Four-week-old male Wistar/ST Clean rats were purchased from Japan SLC Co. Ltd. and were divided into 3 groups of 8 each after preliminary breeding. AIW of pH 9 and 10 was produced by an electrolyzer Mineone ROYAL NDX3 1 OH by Omco Co., Ltd. This model produces AIW by electrolyzing water with calcium lactate added. On the last day of testing, the rats were dissected under Nembutal anesthesia to take blood from the heart by a heparin-treated syringe. As to their organs, the small intestines, cecum and colon plus rectum were taken out from each of them. The cecurn was weighed and cleaned with physiological saline after its contents were removed, and the tissue weight was measured after wiping out moisture. Part of cecal contents was measured its pH, and the rest was used to assay ammonium concentration. The amount of ammonium contained in fresh feces and cecal contents was measured by the Nessler method after collecting it in the extracted samples using Conway's micro-diffusion container. Fecal free-glucose was assayed by the oxygen method after extraction by hot water. Analysis of free amino acids contained in cecal contents was conducted by the Waters PicoTag amino acid analysis system.

Test results and analyses

No difference was found in the rats' weight gain, water and feed intake and feeding efficiency, nor was any particular distinction in appearance identified. The length of the small intestines and colon plus rectum tended to decline in AIW groups.

PH value of cecal contents was higher and the amount of fecal free-glucose tended to be lower in AIW groups than the control group. Since there was no difference in fecal discharge itself, the amount of free-glucose discharged per day was at a low level.

The amount of discharged free-glucose in feces is greater when intestinal fermentation is more intensive, which indicates that intestinal fermentation is more inhibited in AIW groups than the control group.

Ammonium concentration in cecal contents tends to drop down in AIW groups (Fig. 1). This trend was most distinctive in case of fresh feces of one of AIW groups with pH 10 (Fig.2) AIW uptake was found to be inhibitory against ammonium production. In order to study dynamics of amino acids in large intestines, we examined free amino acids in the cecal contents to find out that cysteine level is low in AIW groups whereas isoleucine level is high in one of AIW groups with pH 10, although no significant difference was identified for other amino acids.

Bibliography

1. "Verification of Alkaline Ionized Water" by Life Water Institute, Metamor Publishing Co., 1994, p.46
2. "Official Pharmaceutical Guidelines of Japan, Vol. IT' by Japan Public Documents Association, Hirokawa PublIshin Co., 1996
3. "Science and Technology of Functional Water" (part) by Takashi Hayakawa, Haruffito Tsuge, edited by Water Scienll cc Institute, 1999, pp.109-116
4. "Effective Use of Alkaline Ionized Water" by Takashi Hayakawa, Haruhito Tsuge, edited by Tetsuji Hc kudou, 25th General Assembly of Japan Medical Congress 'Tunctional Water in Medical Treatment", Administratio~ Offices, 1999, pp. 10- 11

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2. Clinical evaluation of alkaline ionized water for abdominal complaints: Placebo controlled double blind tests

Hirokazu Tashiro, Tetsuji Hokudo, Hiromi Ono, Yoshihide Fujiyama, Tadao Baba (National Ohkura Hospital, Dept. of Gastroenterology; Institute of Clinical Research, Shiga University of Medical Science, Second Dept. of Internal Medicine

"Effect of alkaline ionized water on abdominal complaints was evaluated by placebo controlled double blind tests. Overall scores of improvement using alkaline ionized water marked higher than those of placebo controlled group, and its effect proved to be significantly higher especially in slight symptoms of chronic diarrhoea and abdominal complaints in cases of general malaise. Alkaline ionized water group did not get interrupted in the course of the test, nor did it show serious side effects nor abnormal test data. It was confirmed that alkaline ionized water is safer and more effective than placebos.

Summary
Effect of alkaline ionized water on abdominal complaints was clinically examined by double blind tests using clean water as placebo. Overall improvement rate was higher for alkaline ionized water group than placebo group and the former proved to be significantly more effective than the other especially in cases of slight symptoms. Examining improvement rate for each case of chronic diarrhoea, constipation and abdominal complaints, alkaline ionized water group turned out to be more effective than placebo group for chronic diarrhoea, and abdominal complaints.

The test was stopped in one case of chronic diarrhoea, among placebo group due to exacerbation, whereas alkaline ionized water group did not stop testing without serious side effects or abnormal test data in all cases.

It was confirmed that alkaline ionized water is more effective than clean water against chronic diarrhoea, abdominal complaints and overall improvement rate (relief of abdominal complaints) and safer than clean water.

Introduction
Since the approval of alkaline ionized water electrolyzers by Pharmaceutical Affairs Law in 1966 for its antacid effect and efficacy against gastrointestinal disorders including hyperchylia, indigestion, abnormal gastrointestinal fermentation and chronic diarrhoea, they have been extensively used among patients.

However, medical and scientific evaluation of their validity is not established. In our study, we examined clinical effect of alkaline ionized water on gastrointestinal disorders across many symptoms in various facilities. Particularly, we studied safety and usefulness of alkaline ionized water by doubleblind tests using clean water as a control group.

Test subjects and methods
163 patients (34 men, 129 women, age 21 to 72, average 38.6 years old) of indigestion, abnormal gastrointestinal fermentation (with abnormal gas emission and rugitus) and abdominal complaints caused by irregular dejection (chronic diarrhoea, or constipation) were tested as subjects with good informed consent.

Placebo controlled double blind tests were conducted using alkaline ionized water and clean water at multiple facilities. An alkaline ionized water electrolyzer sold commercially was installed with a pump driven calcium dispenser in each of the subject homes. Tested alkaline ionized water had pH at 9.5 and calcium concentration at 30ppm.

Each subject in placebo group used a water purifier that has the same appearance as the electrolyzer and produces clean water.

The tested equipment was randomly assigned by a controller who scaled off the key code which was stored safely until the tests were completed and the seal was opened again.

Water samples were given to each patient in the amount of 200ml in the morning with the total of 50Oml or more per day for a month. Before and after the tests, blood, urine and stool were tested and a log was kept on the subjective symptoms, bowel movements and accessory symptoms. After the tests, the results were analyzed based on the log and the test data.

Conclusion
As a result of double blind clinical tests of alkaline ionized water and clean water, alkaline ionized water was proved to be more effective than clean water against chronic diarrhoea, abdominal complaints (dyspepsia) and overall improvement rate (relief from abdominal complaints). Also, safety of alkaline ionized water was confirmed which clinically verifies its usefulness.

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3. Effect of Electrolytic Water (Ionized Water) Intake on Lifespan of Autoimmune Disease Prone Mice

Research from Texas University

Recent studies on electrolyzed water indicate that anode or acidic water is most effective as disinfectants; whereas, reduced or alkaline water processed through cathode is used as safe drinking water. The present drinking water study was undertaken in two strains of autoimmune disease prone mice to establish the spontaneous disease process and longevity. Weanling MRL/lpr and NZBxNZW [B/W] F1 female mice were provided daily with (1) tap water [pH ~7.5, oxygen reduction potential (ORP)~600+] (2) electrolyzed water with pH of ~9.0 and ORP ~400- and (3) hyper-reduced water with pH~10.0 and ORP~600-. Mice were provided H2O and chow diet ad libitum and weekly body weights and spontaneous deaths were recorded. The mean survival data recorded as days for MRL/lpr mice [25 mice/group] is as follows: (1) tap water 235±25, (2) reduced water 287±40 and (3) hyper-reduced water 346±45 days [<0.05]. In the case of B/W mice [25 mice/group], (1) tap water 269±16, (2) reduced water 298±19 and (3) hyper-reduced 302±18 days. A significantly decreased (<0.05) serum lipid peroxides were observed in mice fed hyper-reduced H2O. Also, the source of water did not alter lymphocyte subsets or their response to mitogens. In summary, hyper-reduced water with pH~10.0 appears to inhibit autoimmune disease of MRL/lpr mice whereas only a modest increased lifespan was noted for B/W mice. The increased lifespan by electrolyzed H2O appears to be related to the changes in free radicals and antioxidant enzyme levels. [Supported in part by Zanix Co. and Mr. Waterman Co., Tokyo, Japan].

Summary:

1. Life long intake of both reduced (pH 9.0) and hyper-reduced (pH 10.0) water caused no harm to mice compared to tap water.
2. Survival is increased significantly by hyper-reduced water in one strain (MRL/lpr).
3. Slight increased life span in the other strain (NZBxNZW F1).
3. Reduced and hyper-reduced water appears to increase T cell numbers, and decrease B cells.
4. Both reduced and hyper-reduced water appears to increase antioxidant mRNA levels.
5. New clinical and animal studies are needed to confirm above results.

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4. Physiological effects of alkaline ionized water: Effects on metabolites produced by intestinal fermentation

by Takashi Hayakawa, Chicko Tushiya, Hisanori Onoda, Hisayo Ohkouchi, Harul-~to Tsuge (Gifu University, Faculty of Engineering, Dept. of Food Science)

We have found that long-term ingestion of alkaline ionized water (AIW) reduces cecal fermentation in rats that were given highly fermentable commercial diet (MF: Oriental Yeast Co., Ltd.). In this experiment, rats were fed MF and test water (tap water, AIW with pH at 9 and 10) for about 3 months. Feces were collected on the 57th day, and the rats were dissected on the 88th day. The amount of ammonium in fresh feces and cecal contents as well as fecal free-glucose tended to drop down for the AIW group. In most cases, the amount of free-amino acids in cecal contents did not differ sign- icantly except for cysteine (decreased in AIW with pH at 10) and isoleucine (increased in AIW with pH at 10).

Purpose of tests

Alkaline ionized water electrolyzers have been approved for manufacturing in 1965 by the Ministry of Health and Welfare as medical equipment to produce medical substances. Alkaline ionized water (AIW) produced by this equipment is known to be effective against gastrointestinal fermentation, chronic diarrhea, indigestion and hyperchylia as well as for controlling gastric acid.*1 This is mainly based on efficacy of the official calcium hydroxide. *2 By giving AIW to rats for a comparatively long time under the condition of extremely high level of intestinal fermentation, we have demonstrated that AIW intake is effective for inhibition of intestinal fermentation when its level is high based on some test results where AIW worked against cecal hypertrophy and for reduction in the amount of short-chain fatty acid that is the main product of fermentation.*3 We have reported that this is caused by the synergy between calcium level generally contained in AIW (about 50ppm) and the value of pH, and that frequency of detecting some anaerobic bacteria tends to be higher in alkaline ionized water groups than the other, although the bacteria count in the intestine does not have significant difference. Based on these results, we made a judgment that effect of taking AIW supports part of inhibition mechanism against abnormal intestinal fermentation, which is one of the claims of efficacy that have been attributed to alkaline ionized water electrolyzers. *4 On the other hand, under the dietary condition of low intestinal fermentation, AIW uptake does not seem to inhibit fermentation that leads us to believe that effect of AIW uptake is characteristic of hyper-fermentation state. Metabolites produced by intestinal fermentation include indole and skatole in addition to organic acids such as short-chain fatty acid and lactic acid as well as toxic metabolites such as ammonium, phenol and pcresol. We do not know how AIW uptake would affect the production of these materials. In this experiment, we have tested on ammonium production as explained in the following sections.

Testing methods

Four-week-old male Wistar/ST Clean rats were purchased from Japan SLC Co., Ltd. and were divided into 3 groups of 8 each after preliminary breeding. AIW of pH 9 and 10 was produced by an electrolyzer Mineone ROYAL NDX3 1 OH by Omco Co., Ltd. This model produces AIW by electrolyzing water with calcium lactate added. On the last day of testing, the rats were dissected under Nembutal anesthesia to take blood from the heart by a heparin-treated syringe. As to their organs, the small intestines, cecum and colon plus rectum were taken out from each of them. The cecurn was weighed and cleaned with physiological saline after its contents were removed, and the tissue weight was measured after wiping out moisture. Part of cecal contents was measured its pH, and the rest was used to assay ammonium concentration. The amount of ammonium contained in fresh feces and cecal contents was measured by the Nessler method after collecting it in the extracted samples using Conway's micro-diffusion container. Fecal free-glucose was assayed by the oxygen method after extraction by hot water. Analysis of free amino acids contained in cecal contents was conducted by the Waters PicoTag amino acid analysis system.

Test results and analyses

No difference was found in the rats' weight gain, water and feed intake and feeding efficiency, nor was any particular distinction in appearance identified. The length of the small intestines and colon plus rectum tended to decline in AIW groups. PH value of cecal contents was higher and the amount of fecal free-glucose tended to be lower in AIW groups than the control group. Since there was no difference in fecal discharge itself, the amount of free-glucose discharged per day was at a low level. The amount of discharged free-glucose in feces is greater when intestinal fermentation is more intensive, which indicates that intestinal fermentation is more inhibited in AIW groups than the control group. Ammonium concentration in cecal contents tends to drop down in AIW groups (Fig. 1). This trend was most distinctive in case of fresh feces of one of AIW groups with pH 10 (Fig.2) AIW uptake was found to be inhibitory against ammonium production. In order to study dynamics of amino acids in large intestines, we examined free amino acids in the cecal contents to find out that cysteine level is low in AIW groups whereas isoleucine level is high in one of AIW groups with pH 10, although no significant difference was identified for other amino acids.

Bibliography
1. "Verification of Alkaline Ionized Water" by Life Water Institute, Metamor Publishing Co., 1994, p.46
*2. "Official Pharmaceutical Guidelines of Japan, Vol. IT' by Japan Public Documents Association, Hirokawa PublIshin Co., 1996
*3. "Science and Technology of Functional Water" (part) by Takashi Hayakawa, Haruffito Tsuge, edited by Water Scienll cc Institute, 1999, pp.109-116
*4. 'Tasics and Effective Use of Alkaline Ionized Water" by Takashi Hayakawa, Haruhito Tsuge, edited by Tetsuji Hc kudou, 25th General Assembly of Japan Medical Congress 'Tunctional Water in Medical Treatment", Administratio~ Offices, 1999, pp. 10- 11

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5. Reduced Water for Prevention of Diseases

Part paper delivered by Dr Shirahata to the Functional Water Symposium in Tokyo by Dr.Sanetaka Shirahata, Graduate school of Genetic Resources Technology, Kyushu University,6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.

It has long been established that reactive oxygen species (ROS) cause many types of damage to biomolecules and cellular structures, that, in turn result in the development of a variety of pathologic states such as diabetes, cancer and aging. Reduced water is defined as anti-oxidative water produced by reduction of water.

Electrolyzed reduced water (ERW) has been demonstrated to be hydrogen-rich water and can scavenge ROS in vitro (Shirahata et al., 1997). The reduction of proton in water to active hydrogen (atomic hydrogen, hydrogen radical) that can scavenge ROS is very easily caused by a weak current, compared to oxidation of hydroxyl ion to oxygen molecule. Activation of water by magnetic field, collision, minerals etc. will also produce reduced water containing active hydrogen and/or hydrogen molecule.

Several natural waters such as Hita Tenryosui water drawn from deep underground in Hita city in Japan, Nordenau water in Germany and Tlacote water in Mexico are known to alleviate various diseases. We have developed a sensitive method by which we can detect active hydrogen existing in reduced water, and have demonstrated that not only ERW but also natural reduced waters described above contain active hydrogen and scavenge ROS in cultured cells. ROS is known to cause reduction of glucose uptake by inhibiting the insulin-signaling pathway in cultured cells. Reduced water scavenged intracellular ROS and stimulated glucose uptake in the presence or absence of insulin in both rat L6 skeletal muscle cells and mouse 3T3/L1 adipocytes. This insulin-like activity of reduced water was inhibited by wortmannin that is specific inhibitor of PI-3 kinase, a key molecule in insulin signaling pathways.

Reduced water protected insulin-responsive cells from sugar toxicity and improved the damaged sugar tolerance of type 2 diabetes model mice, suggesting that reduced water may improve insulin-independent diabetes mellitus.
Cancer cells are generally exposed to high oxidative stress. Reduced water cause impaired tumor phenotypes of human cancer cells, such as reduced growth rate, morphological changes, reduced colony formation ability in soft agar, passage number-dependent telomere shortening, reduced binding abilities of telomere binding proteins and suppressed metastasis.

Reduced water suppressed the growth of cancer cells transplanted into mice, demonstrating their anticancer effects in vivo. Reduced water will be applicable to not only medicine but also food industries, agriculture, and manufacturing industries.

[Also see above for Dr.Sanetaka Shirahata paper " Electrolyzed reduced water scavengers active oxygen species and protects DNA from oxidative damage " ]

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6. Clinical Impovements Obtained From The Intake Of Reduced Water

Extracts from the Presentation At The Eight Annual International Symposium On man And His Environment in Health And Disease on February 24th 1990, at The Grand Kempinski Hotel, Dalls, Texas, USA by Dr. H. Hayashi, M.D. and Dr. M Kawamura, M.D ., on:

THE CONCEPT OF PREHEPATIC MEDICINES

Since the introduction of alkaline ionic water in our clinic in 1985, we have had the following interesting clinical experiences in the use of this type of water. By the use of alkaline ionic water for drinking and the preparation of meals for our in-patients, we have noticed :-

Being confirming clinical improvements, we have always observed changes of stools of the patients, with the colour of their feaces changing from black-brown colour to a brigher yellow-brown one, and the odour of their feaces becoming almost negligible.

The number of patients complaining of constipation also decreased markedly. The change of stool findings strongly suggests that alkaline ionic water intake can decrease the production of putrefield or pathogenic metabolites.

Devices to produce reduced water were introduced into our clinic in May 1985. Based on the clinical experiences obtained in the past 15 years, it can be said that introduction of electrolyzed-reduced water for drinking and cooking purpose for in-patients should be the very prerequisite in our daily medical practices. Any dietary recipe cannot be a scientific one if property of water is not taken by the patients is not taken into consideration.

The Ministry of Health and Welfare in Japan announced in 1965 that the intake of reduced water is effective for restoration of intestinal flora metabolism.

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7. Effects of alkaline ionized water on formation & maintenance of osseous tissues

by Rei Takahashi Zhenhua Zhang Yoshinori Itokawa
(Kyoto University Graduate School of Medicine, Dept. of Pathology and Tumor Biology, Fukui Prefectural University)

Effects of calcium alkaline ionized water on formation and maintenance of osseous tissues in rats were examined. In the absence of calcium in the diet, no apparent calcification was observed with only osteoid formation being prominent. Striking differences were found among groups that were given diets with 30% and 60% calcium. Rats raised by calcium ionized water showed the least osteogenetic disturbance. Tibiae and humeri are more susceptible to calcium deficiency than femora. Theses results may indicate that calcium in drinking water effectively supplements osteogenesis in case of dietary calcium deficiency. The mechanism involved in osteoid formation such as absorption rate of calcium from the intestine and effects of calcium alkaline ionized drinking water on maintaining bone structure in the process of aging or under the condition of calcium deficiency is investigated.

Osteoporosis that has lately drawn public attention is defined as "conditions of bone brittleness caused by reduction in the amount of bone frames and deterioration of osseous microstructure." Abnormal calcium metabolism has been considered to be one of the factors to contribute to this problem, which in turn is caused by insufficient calcium take in, reduction in enteral absorption rate of calcium and increase in the amount of calcium in urinal discharge. Under normal conditions, bones absorb old bones by regular metabolism through osteoid formation to maintain their strength and function as supporting structure. It is getting clear that remodeling of bones at the tissue level goes through the process of activation, resorption, reversal, matrix synthesis and mineralization. Another important function of bones is storing minerals especially by coordinating with intestines and kidneys to control calcium concentration in the blood. When something happens to this osteo metabolism, it results in abnormal morphological changes. Our analyses have been focusing mostly on the changes in the amount of bones to examine effects of calcium alkaline ionized water on the reaction system of osteo metabolism and its efficiency. Ibis time, however, we studied it further from the standpoint of histology. In other words, we conducted comparative studies on morphological and kinetic changes of osteogenesis by testing alkaline ionized water, tap water and solution of lactate on rats.

Three week old male Wistar rats were divided into 12 groups by conditions of feed and drinking water. Feeds were prepared with 0%, 30%, 60% and 100% of normal amount of calcium and were given freely. Three types of drinking water, tap water (city water, about 6ppm of Ca), calcium lactate solution (Ca=40ppm) and alkaline ionized water (Ca =40ppm, pH=9, produced by an electrolyzer NDX 4 LMC by Omco OMC Co., Ltd.) were also given keely. Rats' weight, amount of drinking water and feed as well as the content of Ca in drinking water were assayed every day. On the 19th and 25th days of testing, tetracycline hydrochloride was added to the feed for 48 hours so as to bring its concentration to 30mg/kg. On the 30th day, blood samples were taken under Nembutal anesthesia, and tibiae, humeri and femora were taken out to make non decalcified samples. Their conditions of osteoid formation and rotation were observed using Villanueva bone stain and Villanueva goldner stain.

Three groups that were given different types of drinking water and the same amount of Ca in the feed were compared to find out no significant difference in the rate of weight gain and intakes of feed and drinking water. Alkaline ionized water group had significantly greater amount of tibiae and humeri with higher concentration of calcium in the bones.

The group of 0% calcium in the feed saw drastic increase in the amount of osteoid. There was not much difference by types of drinking water. Almost no tetracycline was taken into tibiae and humeri, although a small amount was identified in ferora. As a result, osteogenesis went as far as osteoid formation, but it was likely that decalcification has not happened yet, or most of newly formed bones were absorbed.

As to the groups of 30% and 60% calcium in the feed, increase in the area of tetracycline take in was more identifiable with higher clarity in descending order of alkaline ionized water, calcium lactate solution and tap water groups. Especially in case of tap water group, irregularity among the areas of tetracycline take in was distinctive. The group of 100% calcium in the feed saw some improvements in osteogenesis in descending order of alkaline ionized water, calcium lactate solution and tap water. In any case, bone formation seemed to be in good condition at near normal level.

Alkaline ionized water was regarded to be effective for improvements of osteogenesis under the conditions of insufficient calcium in the feed. Also, the extent. of dysosteogenesis differed by the region. That is, tibiae and humeri tend to have more significant dysosteogenesis than femora.

In addition, there is a possibility that osteo metabolism varies depending on enteral absorption rate of calcium, adjustment of discharge from kidneys and functional adjustment of accessory thyroid in the presence of alkaline ionized water. We are now studying its impact on calcium concentration in the blood. We are also examining whether it is possible to deter bone deterioration by testing on fast aging mouse models.

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D. Drinking Water Chlorination Studies

  1. References
  2. Recent epidemiological studies
  3. Recent papers on exposure and uptake
  4. Recent studies in laboratory animals
  5. Recent review papers

References

1 Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (2000). Chlorinated Drinking Water and Reproductive Outcomes. 1998 Annual Report of the Committees on Toxicity Mutagenicity Carcinogenicity of Chemicals in Food, Consumer Products and the Environment: pp 7-8. London: Department of Health

2 Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (1993). Epidemiology of Chlorinated Drinking Water and Cancer. 1992 Annual Report of the Committees on Toxicity Mutagenicity Carcinogenicity of Chemicals in Food, Consumer Products and the Environment: pp 55-56 and Correction issued September 1993. London: HMSO

3 Committee on the Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (2000). Drinking Water. 1999 Annual Report of the Committees on Toxicity Mutagenicity Carcinogenicity of Chemicals in Food, Consumer Products and the Environment: pp 59-61. London: Department of Health

4 Swan SH, Waller K, Hopkins B, Windham G, Fenster L, Schaefer C, Neutra RR (1998). A prospective study of spontaneous abortion: relation to amount and source of drinking water consumed in early pregnancy. Epidemiology ; 9: 126-133

5 Toledano MB, Nieuwenhuijsen M, Bennet J, Best N, Whitaker H, Cockings S, Fawell J, Jarup L, Briggs DJ, Elliott P (2001). Chlorination disinfection by products in relation to birthweight in three water areas in England (unpublished draft)

6 Waller K, Swan SH, DeLorenze G, Hopkins B (1998). Trihalomethanes in drinking water and spontaneous abortion. Epidemiology ; 9: 134-140

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Recent epidemiological studies

7 Dodds L, King W, Allen AC, Armson BA, Fell DB, Nimrod C (2004). Trihalomethanes in public water supplies and risk of stillbirth. Epidemiology ; 15: 179-186

8 Dodds L, King W, Woolcott C, Pole J (1999). Trihalomethanes in public water supplies and adverse birth outcomes. Epidemiology ; 3: 233-237

9 Fabiani L, Materazzo F, Ensabella F, Giuliani AR, Patacchiola F, Oleandri V, Leoni V (2003). [Low birth weight, life style of mothers during pregnancy and chlorinated drinking water]. Ann Ig ; 15: 933-43

10 Gallagher MD, Nuckols JR, Stallones L, Savitz DA. (1998). Exposure to trihalomethanes and adverse pregnancy outcomes. Epidemiology ; 9: 484-489

11 Jaakkola JJK, Magnus P, Skrondal A, Hwang B-F, Becher G, Dybing E (2001). Foetal growth and duration of gestation relative to water chlorination. Occup Environ Med ; 58: 437-442

12 Kallen BAJ, Robert E (2000). Drinking water chlorination and delivery outcome - a registry-based study in Sweden. Rep Tox; 14; 303-309

13 King WD, Dodds L, Allen AC (2000). Relation between stillbirth and specific chlorination by-products in public water supply. Env Health Perspec ; 108; 883-886

14 Righi E, Fantuzzi G, Montanari M, Bargellini A, Predieri G, Aggazzotti G (2003). [Exposure to water disinfection by-products and adverse pregnancy outcomes: results of a case-control study carried out in Modena (Italy).] Ann Ig ; 15: 649-62

15 Toledano MB, Nieuwenhuijsen M, Best N, Whitaker H, Hambly P, de Hoogh C, Fawell J, Jarup L, Elliott P (2004). Relation of trihalomethane concentrations in public water supplies to stillbirth and birth weight in three water regions in England. Env Health Perspec ; doi:10.1289/ehp.7111.
http://ehp.niehs.nih.gov/docs/2004/7111/abstract.html

16 Waller K, Swan SH, Windham GC, Fenster L (2001). Influence of exposure assessment methods on risk estimates in an epidemiologic study of total trihalomethane exposure and spontaneous abortion. J Exp Anal and Env Epidem ; 11: 522-531

17 Wright JM, Schwartz J, Dockery DW (2003). Effect of trihalomethane exposure on fetal development. Occup Environ Med ; 60: 173-180

18 Wright JM, Schwartz J, Dockery DW (2004). The effect of disinfection by-products and mutagenic activity on birth weight and gestational duration. Env Health Perspec ; 112: 920-5

19 Yang CY (2004). Drinking water chlorination and adverse birth outcomes in Taiwan. Toxicology ; 198: 249-54

20 Yang C-Y, Cheng B-H, Tsai S-S, Wu T-N, Lin M-C, Lin K-C (2000). Association between chlorination of drinking water and adverse pregnancy outcome in Taiwan. Env Health Perspec ; 108; 765-768

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Recent papers on exposure and uptake

21 Backer LC, Ashley DL, Bonin MA, Cardinall FL, Kieszak SM, Wooten JV (2000). Household exposures to drinking water disinfection by-products: whole blood trihalomethane levels. J Exp Anal and Env Epidem ; 10: 321-326

22 Lynberg M, Nuckols JR, Langlois P, Ashley D, Singer P, Mendola P, Wilkes C, Krapfl H, Miles E, Speight V, Lin B, Small L, Miles A, Bonin M, Zeitz P, Tadkod A, Henry J, Forrester MB (2001). Assessing exposure to disinfection by-products in women of reproductive age living in Corpus Christi, Texas and Cobb County, Georgia: Descriptive results and methods. Envir Health Perspect ; 109: 597-604

23 Miles AM, Singer PC, Ashley DL, Lynberg MC, Mendola P, Langlois P, Nuckols JR (2002). Comparison of trihalomethanes in tap water and blood. Environ Sci Technol ; 36: 1692-1698

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Recent studies in laboratory animals

24 Bielmeier S, Best DS, Guidici DL, Narotsky MG (2001). Pregnancy loss in the rat caused by bromodichloromethane. Tox Sci ; 59: 309-315

25 Bielmeier S, Best DS, Narotsky MG (2004). Serum hormone characterisation and exogenous hormone rescue of bromodichloromethane-induced pregnancy loss in the F344 rat. Tox Sci ; 77: 101-108

26 Chen J, Douglas GC, Thirkill TL, Lohstroh PN, Bielmeier SR, Narotsky MG, Best DS, Harrison RA, Natarajan K, Pegram RA, Overstreet JW, Lasley BL, (2003) Effect of bromodichloromethane on chorionic gonadotrophin secretion by human placental trophoblast cultures. Tox Sci ; 76: 75-82

27 Chen J, Thirkill TL, Lohstroh PN, Bielmeier SR, Narotsky MG, Best DS, Harrison RA, Natarajan K, Pegram RA, Overstreet JW, Lasley BL, Douglas GC (2004). Bromodichloromethane inhibits human placental trophoblast differentiation. Tox Sci ; 78: 166-174

28 Christian MS, York RG, Hoberman AM, Diener RM, Fisher LC, Gates GA (2001a). Biodisposition of dibromoacetic acid (DBA) and bromodichloromethane (BDCM) administered to rats and rabbits in drinking water during range-finding reproduction and developmental toxicity studies. Int J Toxicol ; 20: 239-253

29 Christian MS, York RG, Hoberman AM, Diener RM, Fisher LC (2001b). Oral (drinking water) developmental toxicity studies of bromodichloromethane (BDCM) in rats and rabbits. Int J Toxicol ; 20: 225-237

30 Christian MS, York RG, Hoberman AM, Fisher LC, Ray Brown W (2002) Oral (drinking water) two-generation reproductive toxicity study of bromodichloromethane (BDCM) in rats. Int J Toxicol ; 21: 115-146

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Recent review papers

31 Bove F, Shim Y, Zeitz P (2002). Drinking water contaminants and adverse pregnancy outcomes: A review. Env Health Perspec ; 110 (Suppl 1): 61-74

32 Graves CG, Matanoski GM Tardiff RG (2001). Weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection by-products: A critical review. Reg Tox and Pharm ; 34: 103-124

33 Nieuwenhuijsen MJ, Toledano MB, Eaton NE, Fawell J, Elliott P (2000).
Chlorination disinfection by-products in water and their association with adverse reproductive outcomes. Occup Environ Med ; 57: 73-85

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E. Pain: a need for paradigm change.

Anticancer Res. 1987 Sep-Oct;7(5B):971-89.

Batmanghelidj F .

Foundation for the Simple in Medicine, Lancaster, PA 17603.

From November 1979 to May 1982, I had the "honor" of serving time at Evin political prison, Teheran Iran. Evin is the historical prison which has set the pace of revolution in the country.

At Evin it was discovered that increased regular intake of water improved the clinical picture of peptic ulcer disease. One of the main components of this picture was pain of varying severity, sometimes very severe indeed. Theoretical research to find the physiological reasons for the observed effect of water, in a condition currently classified as disease, has revealed a neurotransmitter, an osmoregulator, a water intake promoter status and a role for histamine.

The action of histamine seems to be coupled to the efficient function of the cation pumps. Histamine and serotonin are involved in the regulation of the body's water balance.

Cellular "free water" insufficiency produces a disturbance of tryptophan metabolism; it is this disturbance and induced functional deficiency altering the homeostatic balance that produces pain and eventually tissue transformation and/or damage.

This pain is being introduced as a signal system denoting free water deficiency of the cell and, therefore, it should be classified as thirst pain.

Histamine and the reninangiotensin system also coordinate the water intake and sodium balance of the body. With the induction of renin-angiotensin system for increase in water intake, threshold rates for water intake and the threshold rates for raising blood pressure seem close.

PMID: 2829704 [PubMed - indexed for MEDLINE]

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F. Pharmaceutical drugs and Personal Care Pollutants in water

1. Emerging chemicals of concern: pharmaceuticals and personal care products (PPCPs) in Asia, with particular reference to Southern China.

Mar Pollut Bull. 2005 Sep;50(9):913-20.

Richardson BJ, Lam PK, Martin M.

Department of Biology and Chemistry, Research Centre for Coastal Pollution and Conservation, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong. bhbrucer@cityu.edu.hk

In many western nations, pharmaceuticals and personal care products (PPCPs) are present in aquatic environments, raising concerns amongst chemists and toxicologists regarding their potential environmental fates and effects. However, there are few published reports of PPCPs in environmental samples from Southeast Asia.

Whilst the environmental toxicology of PPCPs is not well understood, several effects cause concern, such as feminisation or masculinisation by hormones and xenoestrogens, synergistic toxicity from complex mixtures at low concentrations, potential creation of resistant strains in natural bacterial populations, and other potential concerns for human health. Whilst both the presence and distributions of PPCPs in Southeast Asia and China are not well known, observations elsewhere suggest that they may be important contaminants in the aquatic environment. This is particularly emphasised by the enormous production and widespread use of many PPCPs in China, particularly antibiotics utilised in human and veterinary medicine applications. This Viewpoint presents a general description of the issue, characterises the current status of PPCP analyses and reporting in the Southeast Asian region, and proposes a recommended approach for monitoring and chemical assessment of one group of PPCPs, antibiotics, in the aquatic environments of Hong Kong and the Pearl River Delta.

PMID: 16038943 [PubMed - in process]

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2. Occurrence and fate of pharmaceuticals and personal care products (PPCPs) in biosolids.

J Environ Qual. 2005 Jan-Feb;34(1):91-104.

Xia K, Bhandari A, Das K, Pillar G.

Department of Crop & Soil Sciences, 3111 Miller Plant Sciences Building, The University of Georgia, Athens, GA 30602, USA. kxia@uga.edu

Each year, large quantities of pharmaceuticals and personal care products (PPCPs) are used worldwide. Once conveyed to wastewater treatment plants, PPCPs can remain unchanged or undergo partial or complete transformation during wastewater treatment processes before discharge into the environment via effluent and biosolids for land application. Biosolids can be a major sink for some PPCPs. Previous investigations have indicated that land application of biosolids may be a potential important route through which PPCPs enter the environment. However, no information is available on exactly how closely the concentrations of PPCPs in the environmental media are related to the land application of PPCP-containing biosolids. This paper reviews currently available information on the occurrence of PPCPs in biosolids, methods of analysis, the potential fate of PPCPs in biosolids-applied soils, and composting as a potential means for removal of PPCPs from biosolids.

Publication Types:

* Review

PMID: 15647538 [PubMed - indexed for MEDLINE]

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3. Occurrence of pharmaceutical contaminants and screening of treatment alternatives for southeastern Louisiana.

Ann N Y Acad Sci. 2001 Dec;948:80-9.

Boyd GR, Grimm DA.

Civil and Environmental Engineering, Tulane University, New Orleans, Louisiana 70118, USA. gboyd@tulane.edu

Recent studies conducted in Germany, Switzerland, Denmark, Brazil, Canada, the United States, and elsewhere indicate that low-level concentrations of pharmaceuticals and personal-care products (PPCPs) and their metabolites may be widespread contaminants in our aquatic environment. The persistence of pharmaceutical contaminants has been attributed to (1) human consumption of drugs and subsequent discharges from sewage treatment plants, and (2) veterinary use of drugs and nonpoint discharges from agricultural runoff. Contamination of water resources by these compounds, particularly endocrine disrupting chemicals (EDCs), is emerging as an international environmental concern. The long-term effects of continuous, low-level exposure to PPCPs is not well understood. Preliminary data for raw water samples collected from the Mississippi River and Lake Pontchartrain, Louisiana, are summarized. Three PPCP compounds (clofibric acid, naproxen, and estrone) were analyzed using solid-phase extraction, derivatization, and GC/MS. Batch experiments also were conducted to determine equilibrium capacity of activated carbon for clofibric acid. Preliminary results indicate the occurrence of the selected PPCP contaminants in raw water samples at or near method-detection limits. For batch equilibrium experiments, preliminary results indicate that activated carbon potentially can be used to remove clofibric acid from water. More research is needed to develop rapid and reliable methods for PPCP analysis and to determine the effectiveness of treatment processes for removal of PPCP contaminants in water.

PMID: 11795398 [PubMed - indexed for MEDLINE]

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4. Ecotoxicology of human pharmaceuticals.

1: Aquat Toxicol. 2005 Oct 26; [Epub ahead of print]

Fent K, Weston AA, Caminada D.

University of Applied Sciences Basel, Institute of Environmental Technology, St. Jakobs-Strasse 84, CH-4132 Muttenz, Switzerland; Swiss Federal Institute of Technology (ETH), Department of Environmental Sciences, CH-8092 Zurich, Switzerland.

Low levels of human medicines (pharmaceuticals) have been detected in many countries in sewage treatment plant (STP) effluents, surface waters, seawaters, groundwater and some drinking waters.

For some pharmaceuticals effects on aquatic organisms have been investigated in acute toxicity assays. The chronic toxicity and potential subtle effects are only marginally known, however. Here, we critically review the current knowledge about human pharmaceuticals in the environment and address several key questions.

What kind of pharmaceuticals and what concentrations occur in the aquatic environment?

What is the fate in surface water and in STP?

What are the modes of action of these compounds in humans and are there similar targets in lower animals?

What acute and chronic ecotoxicological effects may be elicited by pharmaceuticals and by mixtures?

What are the effect concentrations and how do they relate to environmental levels?

Our review shows that only very little is known about long-term effects of pharmaceuticals to aquatic organisms, in particular with respect to biological targets. For most human medicines analyzed, acute effects to aquatic organisms are unlikely, except for spills. For investigated pharmaceuticals chronic lowest observed effect concentrations (LOEC) in standard laboratory organisms are about two orders of magnitude higher than maximal concentrations in STP effluents. For diclofenac, the LOEC for fish toxicity was in the range of wastewater concentrations, whereas the LOEC of propranolol and fluoxetine for zooplankton and benthic organisms were near to maximal measured STP effluent concentrations. In surface water, concentrations are lower and so are the environmental risks. However, targeted ecotoxicological studies are lacking almost entirely and such investigations are needed focusing on subtle environmental effects. This will allow better and comprehensive risk assessments of pharmaceuticals in the future.

PMID: 16257063 [PubMed - as supplied by publisher]

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