RUSSIAN FEDERATION MINISTRY OF HEALTH AND SOCIAL DEVELOPMENT

RUSSIAN RESEARCH CENTER

OF REHABILITATION AND HEALTH RESORT

«Use of Langvey Deuterium Depleted Water for the treatment of diabetic patients»

Guidelines for physicians

Moscow, 2005

RUSSIAN FEDERATION MINISTRY OF HEALTH AND SOCIAL DEVELOPMENT

RUSSIAN RESEARCH CENTER

OF REHABILITATION AND HEALTH RESORT

APPROVED BY:

A.A. Razumov, professor,

RAMS member,

Chairmen of the Section of rehabilitation, health resort and physical therapy,

Academic Council of the Russian Federation Ministry of Health

and Social Development

«       »___________2005

«Use of Langvey Deuterium Depleted Water for the treatment of diabetic patients»

Guidelines for physicians

Moscow, 2005

 

ANNOTATION

The guidelines for physicians are dedicated to the use of Langvey drinking water with reduced content of heavy isotopes of hydrogen and oxygen for rehabilitation of patients with type 1 or type 2 diabetes mellitus, including patients with the other manifestations of metabolic syndrome.

According to the features of influence of Langvey Deuterium Depleted (Dd) water on clinical signs, anthropometrical values, metabolism of lipids and carbohydrates, lipid peroxidation, its indications for use have been developed depending on the type and severity of diabetes and on the presence of complications allowing the broader use of non-drug treatment options for diabetes mellitus and metabolic syndrome.

The guidelines are intended for polyclinics and health resort institutions.

 

         The guidelines have been developed by Russian Research Center of Rehabilitation and Health Resort of the Russian Federation Ministry of Health (A.N. Razumov, professor, RAMS member, director).

         Authors: E.A. Turova, MD, professor, A.V. Golovach, PhD, E.A. Teniaeva, PhD, I.N. Artikulova, L.V. Tatarinova, I.V. Levchenko.

 

INTRODUCTION

The World Health Organization (WHO) defines diabetes mellitus as an epidemic of a non-infectious disease. WHO specialists believe, that the number of patients with diabetes mellitus (DM) will achieve 300 million worldwide by 2025. There are approximately 8 million diabetic patients in Russian Federation (RF) and this number grows steadily, which prompted the RF Government to accept Federal Task Program, called “diabetes mellitus”, in 1996.

The different etiologic and pathogenetic factors which lead to type 1 DM and type 2 DM determine the different treatment tactics. Type 1 DM has been identified as immundeficient type, characterized by absolute insulin insufficiency and requiring insulin replacement therapy. A major role in the pathogenesis of type 2 DM is assigned to insulin resistance and compensatory hyperinsulinemia, which results in relative insulin insufficiency. Insulin resistance is, in turn, induced by obesity. The treatment of patients with type 2 DM is based on diet, increased physical activity and on the use of oral drugs of various groups; it is aimed to decrease blood glucose level, body weight, the amount of abdominal and visceral fat and to increase insulin sensitivity in peripheral tissues.

A novel group of drugs – insulin sensitizers – has been developed to treat insulin resistance. Short action secretagogues were developed for correction of postprandial hyperglycemia which is the major cause of late vascular complications of diabetes. However, current therapeutic options do not eliminate problems in treatment of diabetic patients. Therefore, methods of balneotherapy are becoming increasingly important in complex treatment of DM; when used appropriately and timely, they contribute to the increase of treatment efficacy, maintaining stable compensation, and to prevention of disease progression and complications development.

Waters with various chemical composition used in water treatment of DM have complex mechanism of action, which depends both on water composition and its mineralization and temperature. The role of water in the body is believed to be the direct influence on the formation and stabilization of native structure of biopolymer macromolecules, biomembranes and various more complex permolecular structures. In addition, water affects the efficacy of biological reactions in the body; at that, changes in protein conformation and in free energy of the system are associated with simultaneous changes in molecular structure and in aqueous component – change in water status.

The most important recent finding was the fact, that biologically active water can switch the body cells from low physiological activity state or even from disease to normal function. This provides an opportunity to use water for non-pharmacological control of a large number of various matabolic reactions taking place in aqueous medium, which is common for all cells. This effect was also found in water with reduced (as compared to usual values) content of heavy isotopes of hydrogen and oxygen (hereinafter, the “Dd water”). Activation of membrane proteins is possibly due to the effect of Dd water, while normalization of transmembrane potential permits to increase insulin-dependent facilitated diffusion of glucose into the cells. Changes in physicochemical properties and structure of water are known to alter the macroscopic properties of biological membranes and the features of membrane proteins. Decrease in deuterium extracellular level can affect conformational mobility and activity of transfembrane proteins due to cleavage of part of stronger hydrogen bonds formed previously by deuterium atoms. Experiments showed changes in transmembrane potential and intracellular pH of herbal cells after the plant was placed in a Dd water, indicating directly the activation of membrane proteins by the Dd water.

Langvey Dd water is a hydrocarbonate calcium-magnesium water with Ca2+ / Mg2+ ratio of 3 : 1. A specific feature of Dd water is reduced (as compared to common water) content of deuterium and oxygen–18. Other parameters of Dd water are in accordance with the requirements for the highest quality water stated in SanPin 2.1.4.1116 – 02. Langvey Dd water is characterized by high purification regarding impure elements and by optimal redox potential as well. Besides the low content of deuterium and oxygen-18, specific physicochemical properties of Langvey Dd water include lower density, higher dissolving capacity and higher structural homogeneity.

Use of Dd drinking water for the treatment of DM patients is reasonable due to its complex effect on the body (activation of metabolic processes, immune system correction, detoxication etc.), to its favorable effect on concomitant diseases, and to its safety, good tolerability, absence of side effects or addiction as well.

INDICATIONS

  1. Type 2 diabetes mellitus
  2. Type 1 diabetes mellitus
  3. Excessive weight
  4. Grade 1-3 alimentary and constitutional obesity
  5. Impaired glucose tolerance
  6. Dislipidemia

CONTRAINDICATIONS

None known.

MATERIAL AND TECHNICAL REQUIREMENTS FOR THE METHOD

 

“LANGVEY Deuterium Depleted» drinking water, Manufacturer: MTC Iceberg, Ltd.,Russia.

Specification 0131-001-58681039-02, 09.04.2003. Sanitary and epidemic report № 77.99.11.013.Т.000295.03.03, 17.03.2003.

         Specification 0131-001-58681039-02 (amendment № 1, 02.04.2004). Sanitary and epidemic report № 77.99.15.013.P.000431.03.04, 16.03.2004.

 

METHOD DESCRIPTION

Langvey Dd drinking water with reduced content of hydrogen and oxygen heavy isotopes was administered in combination with background hypoglycemic therapy.

The daily dose of water was 1 l, the first fasting dose of 200 ml was taken in the morning, subsequent doses of 200 ml each were taken 30 min prior to each meal.

 One treatment cycle is 4 weeks.

TREATMENT METHOD

 

The daily dose of Langvey Dd water was 1 l, the first fasting dose of 200 ml was taken in the morning, subsequent doses of 200 ml each were taken 30 min prior to each meal for 4 weeks.

In decompensated diabetics the daily dose can be increased to 2 l and the cycle of treatment can be prolonged up to 12 weeks.

INDICATIONS

 Langvey drinking water with reduced content of hydrogen and oxygen heavy isotopes can be recommended for use in patients with moderate-severe or severe type 1 DM regardless of carbohydrate metabolism compensation level; in patients with mild, moderate or severe type 2 DM regardless of carbohydrate metabolism compensation level; in patients with excessive weight or with grade 1-3 obesity, hypercholesterolemia, hypertriglyceridemia, stage 1-2 hypertension.

CONTRAINDICATIONS

 

None known.

EFFICACY OF COMBINED THERAPY USING DEUTERIUM dEPLETED WATER IN PATIENTS WITH TYPE 1 OR TYPE 2 DIEBETES MELLITUS

Efficacy of Langvey Dd water was assessed in 50 DM patients, 20 out of them had type 1 DM and 30 had type 2 DM.

Patients with type 1 DM were women only, aged 30 to 67 (mean age 52.2 years) with prior history of the disease ranging from 3 to 29 years (mean duration of disease 15.5 years). Hypertension was revealed in 9 (45 %) subjects: 2 out of them had stage 1 hypertension (H) and 7 had stage 2 H. - 7. Coronary artery disease (CAD) was found in 4 female patients. Grade 2 obesity accompanied by chronic insulin overdose was present in 6 (30 %) subjects. Dislipidemia was revealed in 12 (60 %) patients.

Patients with type 2 DM included 20 (66 %) women and 10 (34 %) men aged 47 to 66 (mean age 54.2 years) with prior history of the disease ranging from 3 to 15 years (mean duration of disease 8.2 years). Hypertension was found in all type 2 DM patients: 12 out of them had stage 1 H, another 18 patients had stage 2 H. CAD was found in 6 patients. All participants (100%) had obesity. Grade 1 obesity was diagnosed in 6 subjects, grade 2 obesity – in 14 subjects, grade 3 obesity – in 10 subjects Abdominal obesity was found in 19 (63 %) patients, gynoid obesity – in 11 (37 %) patients. Various disorders of lipid metabolism were observed in 23 (76 %) patients.

No correction of hypoglycemic therapy was performed during the study on Dd water.

All patients participating the study were assigned to 4 groups comparable in sex, age, duration and severity of disease, clinical manifestations and in all the values assessed:

Group 1 (n=10) – patients with type 1 DM receiving background hypoglycemic therapy and Langvey Dd water;

Group 2 (n=10) – patients with type 1 DM receiving background hypoglycemic therapy and placebo water (control group);

Group 3 (n=20) – patients with type 2 DM receiving background hypoglycemic therapy and Langvey Dd water;

Group 4 (n=10) - patients with type 2 DM receiving background hypoglycemic therapy and placebo water (control group).

Control group patients received Sofrinskaya natural drinking water with similar mineralization and content of basic micro- and macro-elements (manufactured by ZEMTEX, Ltd Specification 0131-001-50189646-2000, 08.04.2002. Sanitary and epidemic reports № 77.99.04.013.Т.000275.04.02, 05.04.2002, № 50.37.05.000.М.000935.05.03, 23.05.2003).

The effect of Langvey-100 Dd water in type 1 DM patients.

 

Mean height of the patients evaluated was 158.22 cm. Baseline weight was 77.32±5.47 kg, baseline body mass index (BMI) was 31.92±2.18, fat tissue content was 41.93±1.31%. After Dd water therapy cycle body mass significantly decreased to 76.62±5.3 kg. Changes in other anthropometrical values (BMI and fat tissue content) were non-significant. No significant changes in the values studied were observed in the control group.

 At baseline the patients with type 1 DM had significant baseline elevation of mean value of systolic blood pressure (SBP) to 158.2±9.78 mm HG and mean value of diastolic blood pressure (DBP) to 102.5±5.96 mm Hg. After treatment there was a trend to the decrease in mean value of SBP to 142.62±7.69 and in mean value of DBP to 91.2±4.97 in the group. No changes in BP values were observed in control group.

 At baseline glycemic profile in type 1 DM patients showed fasting hyperglycemia (9.22±1.07 mmol/l), as well as hyperglycemia 1 h (10.96±0.99 mmol/l) and 2 h (8.55±0.94 mmol/l) after meal, glucosuria level was 15.67±3.5 g/day. Hormone assay performed at baseline revealed normal level of immunoreactive insulin (IRI), increased content of anti-IRI antibodies (IRI-Ab) and decreased level of serum C-peptide. In Dd water group glucose level 1 h after meal significantly decreased to 9.08±0.64 mmol/l, and daily glucosuria significantly decreased to 10.1±3.16 g/day; changes in other values were non-significant. There were no statistically significant changes in values of carbohydrate metabolism in control group.

As stated above, 60% of type 1 DM patients had various disorders of lipid metabolism at baseline. There were no significant changes in these values following Dd water or placebo water therapy cycle.

At baseline patients with type 1 DM had 1.6-fold increase in functional activity of neutrophiles as measured by spontaneous HCT-test, 1.3-fold increase in levels of diene conjugates (DC) and malonic dialdehyde (MDA), suggesting the increase in level of active oxygen forms (AFO) and activation of lipid peroxidation (LP). In 2 patients with ketonuria the elastase activity was slightly elevated, other patients commonly had 1.3-fold decrease in enzyme activity, the activity of elastase inhibitor was within the normal range, indicating adaptive response of the body and reduction of destructive changes. All patients with type 1 DM had 1.3-fold increase in a2 – MG activity, suggesting high vascular permeability. Thus, analysis showed, that type 1 DM patients presented increase in levels of active forms of oxygen and activation of primary and end products of LP accompanied by reduction of signs of connective tissue destruction and increased vascular permeability specific to autoimmune diseases.

Following Dd water therapy course decrease in functional activity of neutrophiles to the upper limit and progressive decrease of elastase activity were observed in patients with type 1 DM; a1 - proteinase inhibitor (a1 – PI) activity was within the normal range, a2 – macroglobulin (a2 – MG) activity returned to normal value, DC and MDA levels did not change. At the same time, the study revealed decrease in levels of active oxygen forms and reduced destruction coefficient, normalization of vascular permeability, indicating stabilization of cellular and lysosome membranes.          Normalization of a2 – MG level results in the decrease in vascular permeability, which is crucial for blocking autoimmune processes in type 1 DM patients. The fact, that LP products level remained unchanged, suggests, that the antioxidant effect of Dd water is based on the influence on the mechanisms of AFO generation without inactivation of the existing radicals, which is possibly due to residual events of “oxidation burst” taking place shortly after the treatment cycle.

The effect of Langvey-100 Dd water in type 2 DM patients.

 

Mean height of the patients evaluated was 166.42 cm. Mean body mass at baseline was 94.52±4.37 kg, mean body mass index at baseline was 35.9±1.21, fat tissue content was 45.99±1.11 % and impedance value was 471.56±15.02. After Dd water therapy cycle the patients had significant decrease in the body mass to 93.12±5.01 kg, in BMI to 34.03±1.35, in fat tissue content to 45.00±1.1 % (from 41.98±2.02 kg to 40.12±3.13 kg), increase in impedance to 476.7±13.2. Changes in other anthropometrical parameters (fat-free body mass and water content) were non-significant. No significant changes in the values studied were observed in the control group.

Patients with type 2 DM had increased SBP (to 164.2±8.54 mm Hg) and DBP (to 106.5±6.23 mm Hg) mean values at baseline. Dd water therapy cycle in this group resulted in decrease in mean SBP to 152.65±6.65 and in mean DBP to 90.6±5.65 mm Hg. No changes in BP values were observed in control group.

Glycemic profile study revealed increase in all glycemia and glucosuria values in type 2 DM patients at baseline. Hormone assay showed normal values of IRI, IRI-Ab and C-peptide at baseline. Patients, who received Dd water, had significant decrease in all parameters of glycemic profile: fasting glucose (from 8.67±0.41 to 6.86±0.36 mmol/l), glucose level 1 h after meal (from 11.11±0.54 to 8.33±0.42) and 2 h after meal (from 9.24±0.59 to 6.59±0.36 mmol/l), as well as decrease in daily glucosuria (from 14.41±3.07 to 5.13±1.76 g/day). Changes in other parameters were non-significant. There were no statistically significant changes in values of carbohydrate metabolism in control group.

As stated above, 76 % of type 2 DM patients had various disorders of lipid metabolism at baseline. After Dd water therapy cycle there was a significant decrease in b - lipoproteins level from 8.67±0.67 to 7.52±0.58 g/l and atherogenic coefficient decreased from 2.72±0.25 to 2.33±0.25, a trend to the decrease in initially elevated level of triglycerides from 2.85±0.46 to 1.93±0.23 mmol/l was observed as well. After placebo water therapy cycle there were no significant changes in parameters of lipid metabolism.

In randomly selected patients (40%) with type 2 DM assessment of blood rheological properties was performed. It showed significant decrease in initially elevated AFO-induced platelet aggregation index from 45.15 to 39.81% and in adrenaline-induced platelet aggregation index from 45.25 to 39.06%; fibrinogen level decreased from 5.28±0.25 to 4.73±0.23 g/l and hematocrit level decreased from 55.9 to 47.66%. Initially decreased serum heparin tolerance (529.93 s) increased to normal value (585.6 s).

In type 2 DM patients there was normal functional activity of neutrophiles. Levels of DC and MDA tended to increase. There was a 1.3-fold decrease in elastase activity, however, 2 patients had increased a1 – PI activity suggesting disorders of elastase-inhibitor system. In other patients there was a 1.4-fold decrease in a1 – PI activity as compared to physiological range suggesting its intensive consumption during elastase inactivation. Mean destruction coefficient was at the upper limit of the normal range, and it was above the limit in 2 patients. This fact indicates, that type 2 DM patients, despite the low elastase level, have disorders of elastase-inhibitor activity associated with destruction of elastin and collagen fibers of connective tissue and angiopathy development. Activity of a2 – MG was declined, suggesting proteolysis activation. Therefore, patients with type 2 DM had nearly normal functional activity of neutrophiles and level of LP products, but there was a disorder and failure in the system of proteinases/inhibitors.

After Dd water therapy cycle type 2 DM patients had significant increase in HCT-test values (still remaining within the normal range), DC and MDA levels were similar to those in control group. Elastase activity tended to increase, but remained below the normal physiological range. Activity of elastase inhibitor was within control range, but per patient analysis showed, that initially elevated activity decreased, while in contrast initially low activity increased. This fact suggests normalizing effect of Dd water on a2 – MG activity. In type 2 DM patients Dd water therapy resulted in the increase in functional activity of neutrophiles and elastase activity values, which still remained within physiological range. The increase in elastase inhibitor activity paralleled the increase in elastase activity.

Patients with type 1 or type 2 diabetes mellitus receiving Langvey Dd water had no signs of intolerance or any other adverse reactions. On the contrary, the patients mentioned pleasant and soft taste of the water. There were no symptoms of gastric or intestinal dyspepsia.

The studies showed, that type 1 DM patients receiving Langvey Dd water therapy presented significant decrease in glucosuria values (1.5-fold), body mass and glucose level 1 h after meal; there was a trend towards the decrease in SBP and DBP levels. At the same time, lipide profile remained unchanged.

Analysis of the effect of Dd water on the functional activity of neutrophiles, elastase inhibiting activity of serum and LP suggests, that Dd water has favorable effect on the course of autoimmune process in type 1 DM patients.

In type 2 DM patients Dd water lead to more marked biochemical changes: blood glucose, glucosuria levels and some atherogenic parameters of lipid profile were decreased. There was the decrease in initially elevated SBP and DBP values, as well as in clinically relevant anthropometrical parameters: body mass, BMI and fat tissue content. The changes in functional activity of neutrophiles, serum elastase-inhibitor activity and LP in type 2 DM patients were associated with activation of adaptive processes.

 

CONCLUSION

Metabolic disorders were found virtually in all diseases and frequently precede their manifestation. In view of the fact, that the water holds a central position in metabolic processes of the body, its role in the prevention and treatment of a number of serious conditions, including diabetes mellitus and metabolic syndrome, can hardly be overestimated.

Deuterium content (and, accordingly, content of heavy water) in human biological fluids depends on the geographic location and is determined mostly by its content in the drinking water. Single administration of 250 ml Dd water was found to have no effect on deuterium concentration in human plasma. At the same time, 3-4 weeks Dd water therapy cycle leads to significant decrease in deuterium level in human plasma. Biological effects of Dd water and its effect on the body are apparently due to heavy water clearance from the body and, therefore, to the change in organization and properties of the aqueous environment of the body. The speed and the degree of heavy water clearance from the body depend on the patient’s body mass, severity of metabolic disorders, type of Langvey water (Langvey – 100 or Langvey – 60) and on duration of treatment.

Decreased level of heavy water in biological media is possibly accompanied by the increase in functional activity of cells, organs and various systems of the body due to normalization of metabolic processes, energy homeostasis and to increase in adaptive reserves of different functional systems of the body.

Langvey Dd drinking water with reduced content of heavy hydrogen and oxygen isotopes is well tolerated, exhibits hypotensive, hypoglycemic and hypolipidemic effects, which are particularly pronounced in type 2 DM patients.

Dd water can be recommended for use as an adjunctive treatment in type 1 or type 2 DM patients, including those with excessive weight, obesity or dislipidemia.

References

S.I. Aksenov. The features of influence of water on biological structures. Inhibition of cell’s vital functions. Riga. 1987, p.55-71.

S.I. Aksenov. Water and its role in regulation of biological processes. Moscow, Nauka publishers, 1990, p. 115

I.N. Varnavsky. New technology and purified biologically active therapeutic drinking water unit. Doctoral thesis. // Moscow, 2000.

Water – a cosmic phenomenon. – Edited by Yu.A. Rakhmanin, V.K. Kondratov, Moscow, RANS, 2002.

A.V. Golovach, E.A. Turova. Report on the results of the clinical trials with Langvey Deuterium Depleted Water. Research Center of Rehabilitation and Health Resort, Russian Federation Ministry of Health, Moscow, 2003 (23.01.03).

A.V. Golovach, B.K. Akimov. The use of “Langvey” water in patients with type 2 diabetes mellitus. All-Russian Forum “Current problems of Rehabilitation, Health Resort and Physical Therapy”, Kislovodsk, 2003, p. 70.

A.V. Golovach, E.A. Turova. Report on the results of the clinical trials with Langvey Dd water. Research Center of Rehabilitation and Health Resort, Russian Federation Ministry of Health, Moscow, 2003 (21.07.03).

M.M. Ginzburg, N.N. Kryukov. Obesity. Its role in the development of metabolic syndrome. Prevention and treatment. Moscow, Medpraktika-M publishers, 2002.

I.I. Dedov, M.V. Shestakova. Diabetes mellitus. Moscow, 2003, p.p. 133 – 178, 304 – 318.

I.I. Dedov, G.A. Melnichenko Obesity. Moscow, 2004, p.p. 16–19, 44–77, 378–405.

A.V. Dmitriev, L.P. Rodionova, L.L. Goncharova, V.S. Ivanova. The effect of freshly thawed water from Antarctic ice on the activity of blood enzymes in vitro. “Fluctuation in biological systems”, Collected papers of Leningrad Sanitary and Hygienic Medical Institute, 1986, p.66.

G.N. Zatsepina. System of electrical regulation of vital processes. Moscow, Moscow University publishing house, 1992.

G.N. Zatsepina. Physical properties and structure of water. Moscow, Moscow University publishing house, 1998.

V.A. Kondratyuk. The effect of drinking water with various ratio of calcium and magnesium on the consumer’s body. Cosmic Biology and Aviacosmic Medicine, XII-th conference, Moscow, 1998, v 1, p.320.

V.N. Lobyshev, L.P. Kalinichenko. Isotopic effects of D2О in biological systems. Moscow, Nauka publishers, 1978.

V.N. Lobyshev. Possible causes of the formation of bioactive water after various treatment methods. VI-th International Congress «Water: ecology and technology «AQUATECH – 2004» - materials of congress, part II. Moscow, June 1-4, 2004 – p. 977.

A.K. Martynov, I.V. Artemkina, A.A. Timakov, T.I. Moskvucheva. Assessment of biological activity of deuterium depleted water. Materials of Interdisciplinary Conference with International Participants «New biocybernetic and telemedical technologies of the XXI-st century», Petrozavodsk, June 23-25, 2003, p. 57.

Yu.A. Rakhmanin, R.I. Mikhailova, A.A. Timakov, T.I. Moskvicheva, G.A. Kalabin. Several properties of deuterium depleted water. Materials of the VI-th Congress «Water: ecology and technology «AQUATECH-2004», Moscow, 2004, part 2, p.799.

Yu.A. Rakhmanin, R.I. Mikhailova et al. Assessment of biological activity of water with reduced content of deiterium (deuterium depleted water). Abstracts of the XVI-th International Forum «Medical and ecological safety, rehabilitation and social protection of population». Moscow, 2004, p.152.

Yu.A. Rakhmanin, V.K. Kondratov. Assessment of structure and biological activity of water containing 10-1000 ppm D2О using IR spectroscopy. Report of the Sysin Research Institute of Human Ecology and Environmental Hygiene, Russian Academy of Medical Sciences, Ekaterinburg-Moscow, 2005.

Yu.E. Sinyak, A.I. Grigoryev. Optimal isotopic composition of biogenic chemical elements aboard a manned space vehicles - «Aviacosmic and ecological medicine», 1996, V.30, №4, p.p.26-30.

Yu.E. Sinyak, A.I. Grigoriev, V.V. Gaydadymov, E.I. Mednikova, Z.N. Lebedeva, E.I. Guskova. A method to produce non-deiterium water and assessment of its effect on physiological state of japanese quail. Cosmic biology and aviacosmic medicine. Materials of the XI-th meeting, 1998, V. II, p. 201.

Yu.E. Sinyak, M.A. Levinskikh, V.V. Gaydadymov, E.I. Guskova, O.B. Signalova, T.A. Derendyaeva. The effect of deuterium depleted water on cultivation of higher plants: Arabidopsis thaliana and Brassica rapa. «Organism and environment: life support and human protection in extreme conditions», materials of the Russian Conference. Moscow, 2000, V. 2, p.90.

A.A. Timakov, T.I. Moskvicheva, G.A. Kalabin. Study of structure and properties of partially deuterium depleted water. Abstracts of the IX-th Russian Research Meeting «Physicochemical processes in molecular selection», Moscow, 2004, p.37.

A.A. Timakov, T.I. Moskvicheva. Drinking water with reduced content of deiterium as compared to natural sources. Bottled drinking water. Information digest №5, Moscow, 2004 – p. 109.

A.A. Timakov, G.A. Kalabin, O.S. Vakhrusheva, V.V. Keshelayeva. An ability to diagnose oncological diseases using the measurement of isotopic composition of hydrogen in biological fluids. «Actual Problems of Ecology and Nature Management», Conference proceedings, Moscow, 2005.

E.A. Turova, A.V. Golovach, A.A. Timakov, T.I. Moskvicheva. Basic effects of deuterium depleted drinking water. Abstracts of the XIV-th International Forum «Medical and Ecological Safety, Rehabilitation and Social Protection of population», Croatia, 2003, p.176.

E.A. Turova, A.V. Golovach, A.A. Timakov, B.K. Akimov. The effect of water with reduced content of heavy hydrogen and oxygen isotopes in patients with metabolic syndrome. Materials of Interdisciplinary Conference with International Participants «New biocybernetic and telemedical technologies of the XXI-st century», Petrozavodsk, June 23-25, 2003, p. 28.

E.A. Turova, A.V. Golovach, A.A. Timakov, B.K. Akimov. The use of Langvey water in patients with type 2 diabetes mellitus. Proceedings of the II-nd International Congress «Water, beverages and juice», Moscow, 2004, p. 27.

E.A. Turova, A.V. Golovach, A.A. Timakov, B.K. Akimov. The use of partially deuterium depleted (light) water Langvey for rehabilitation of patients with various manifestations of metabolic syndrome or with diabetes mellitus. Materials of the I-st All-Russian Meeting «Rehabilitation and Health-Resort Treatment in Endocrinological Patients», Moscow, 2005, p.14.

N.S. Sergeyeva, I.S. Sviridova. Assessment of the effect of deuterium depleted water on the toxic effect of cytostatics in mice. Report of the Gertsen Moscow Research Institute of Oncology, Moscow: 2004 – p. 38.

E.E. Fesenko et al. Immunomodulating properties of bidistilled modified water. Biophysics, 2001, V. 46, 2 edition, p. 353.

Yu.A. Fedorov. Stable isotopes and evolution of hydrosphere. Moscow, Istina publishers, 1999

V.K. Frolkov, N.D. Polushina et al. Hormonal regulation of carbohydrate metabolism and metabolic effects of physical therapy. Essentuki, 1977.

V.K. Frolov, Modern concepts of therapeutic and prophylactic properties of mineral waters. Proceedings of the II-nd International Congress «Water, beverages and juices», Moscow, 2004, p. 22.

Yu.P. Shvetsov, V.V. Novikov et al. Decrease of RNA-dependent DNA polymerase activity of the recombinant HIV reverse transcriptase in bidistilled modified water. Biophysics, 2001, V. 46, version 2, p.p. 379-380.

Blaga, Lucia Blaga. The deuterium content of human metabolic fluids in relation with human metabolic proceses (in Romania), IFA-Bucuresti, ScientificReport (1978), 1-4.

Berdea Р., Gristina Dobrota P., Cosma C., Stela Cuna. Growing rate desrease of the maize embryos spouted in deuterium-deplеted water (20 ppm), Collogvium Spectroscopicum Internationale XXXI, Ankara, Turkey, sept.5-10, (1999), (Fbstr.), 123.

Berdea P., Stela Cuna, Cazacu M., Tudose M. Deuterium variation of human blood serum/ Studiauniversitatis dades-bolyal, special issue, 2000.

Berdea P., Stela CunaCazacu, M., Tudose M. Deuterium depletion in blood, blood plasma and neoplasm tissue from patients diagnosis and treatment implications, www.itim-cj.ro/PIM/2003/FullText/poster/Berdea.doc

Bild W.and at “Research concerning the radioprotective and immunostimulating effects of deuterium-depleted water”, Rom. J. Physiol., 1999.36, 3-4. p.p. 205-218.

Padurari I., Jerca L., Berbec A., Wild W. Deuterium Depleted Water Effects over Some Oxidative Stress Parameters. Roum. Biotech. Lett. Vol.5, No.4, 2000, p.p.273-278.

Pricope F. et al. Effect of deuterium-deplеted water on reproduction of rainbow frout. Environ Chem Lett (2003) 1.

Somlyai G., Laskay G. and al. Naturally occurring deuterium may have a central role in cell signaling. In: Heys J.R. Melillo D.G. Synthesis and applications of isotopically labeled compounds lohn Wiley & Sons Ltd., 1998, 137-141.

Somlyai G. “The biological effect of deuterium depletion”, Budapest, Akademiai Klado, 2002.

Zimmermann U., Cegla U. Der Deuterium – und Sauerstoff-18-Gehalt der Körperflüssigkeit des Menschen und seine Änderung bei Ortswechsel. Naturwissenschaften 60, 243-246с, 1973.