Research on Deuterium Depleted Water (DDW)

IMPORTANT NOTICE

The following research abstracts are reproduced from published peer-reviewed scientific literature for educational purposes only.
These studies were conducted independently of Yavelle
Yavelle does not claim that its products replicate the results of these studies.
This page does not constitute medical advice.
Yavelle 25ppm Deuterium-Depleted Water is not intended to diagnose, treat, cure, or prevent any disease. Always consult your healthcare provider before making changes to your health routine.

Deuterium Depleted Water and Cancer Research: Human Trials

Deuterium Depletion may delay the progression of prostate cancer

András Kovács, et al.

Journal of Cancer Therapy, Vol. 2 No.4(2011), Article ID:7799,9 pages

Abstract

Deuterium-depleted water (DDW) is a new promising agent in cancer therapy. The efficiency of the method is based on the discovery that cancer cells are extremely sensitive to the depletion of deuterium (D), which might cause necrosis of the tumour.

The purpose of this study was to show the efficacy of D-depletion in prostate cancer (PC) patients. In the double blind, four-month-long, randomised Phase II clinical trial, the daily water intake was replaced with DDW in 22 PC patients. The other 22 PC patients took normal water while both groups received the same forms of conventional treatment. In the retrospective study, 91 DDW-treated PC patients were evaluated, and the median survival time (MST) in the subgroups was calculated. The time course of changes in DDW dose and PSA is presented in two cases.

In the prospective trial, seven patients in the treated group and one patient in the placebo group achieved a partial response (p = 0.046). In the treated group, the net decrease in the prostate volume was three times higher (160.3 cm3 vs. 54.0 cm3 ; p = 0.0019), urination complaints ceased at a higher rate (8 vs.0 patients, p = 0.0041), and the one-year survival rate was also higher (2 vs 9 deaths; p = 0.034).

The 91 retrospectively evaluated patients achieved an MST of 11.02 years, despite the fact that 46 of them suffered from distant metastasis. In the two monitored patients, a drop in PSA level correlated with the DDW intake.

In summary, D-depletion prolonged MST in patients with PC. The method proved to be safe, thus its integration in the PC cure as an adjuvant or complementary therapy would be considered.

Deuterium-depleted water (DDW) effects on the survival of lung cancer patients and expression of Kras, Bcl2, and Myc genes in mouse lung

Gyöngyi Z, et al.

Nutr Cancer. 2013;65(2):240-6.

Abstract

Although advances in cancer therapies continue to develop, the shortness of the survival of lung cancer patients is still disappointing. Therefore, finding new adjuvant strategies is within the focus of cancer cure.

Based on observations that deuterium depletion inhibits the growth of cancer cell lines and suppresses certain protooncogenes, we have conducted a clinical study in 129 patients with small cell and non-small cell lung cancers who consumed deuterium-depleted drinking water (DDW) as a nontoxic agent in addition to conventional chemotherapy and radiotherapy.

Median survival time (MST) was 25.9 mo in males and 74.1 mo in female patients; the difference between genders was statistically significant (p < 0.05). Median survival of subjects with brain metastasis was 27.1 mo. Cumulative 5-yr survival probabilities were 19%,52%, and 33% in males, females, and all patients with brain metastasis, respectively.

Gene expression analysis in mouse lung indicated that DDW attenuates 7,12-dimethylbenz(a)anthracene (DMBA)-induced expression of Bcl2, Kras, and Myc in females.

In conclusion, DDW counteracts the DMBA-induced overexpression of Bcl2, Kras and Myc genes in mouse lung, and it may extend the survival of lung cancer patients as a nontoxic anticancer dietary supplement, especially for women with tumours overexpressing cancer-related genes, because MST of the DDWconsuming group was 2-4 times longer than it is generally observed in lung cancer patients.

Deuterium variation of human blood serum

P. Berdea, et al.

Studia Universitatis Babes-Bolyai, Physica, Special Issues, 2001

Abstract

The deuterium content of healthy human blood plasma is about 149-150 ppm. Some variations of deuterium content with age and sex were observed in blood plasma. We report for the first time the variation of deuterium content of the blood plasma of patients with cancer disease.

The deuterium content of the blood plasma of cancerous humans is diminished by about 5-7 ppm compared with that of healthy individuals. The tumour cells have a higher speed of growth than the normal cells, and this results in consuming a greater quantity of deuterium.

The replacement of tap water with deuterium-depleted water in drinking water for the mice diminishes the growth rate of the tumours, and the slight increase in the deuterium concentration stimulates this growth.

A retrospective study of survival in breast cancer patients undergoing deuterium depletion in addition to conventional therapies

Krempels K et al

Journal of CancerResearch & Therapy 2013, 1(8):194–200

Abstract

There is increasing evidence that the heavy isotope of hydrogen, deuterium (D), has a pivotal role in cell signaling and that its depletion through the replacement of normal drinking water with deuterium-depleted water (DDW) results in tumour necrosis. The impact of D-depletion on breast cancer outcome was studied retrospectively. The normal daily water intake (150 ppm D) of 232 breast cancer patients was replaced with DDW (65-105 ppm D) for at least 91 days, without altering conventional treatment regimens.

According to staging at initial diagnosis, patients with early-stage breast cancer (n158) achieved a median survival time (MST) of 217 months (18.1 years), compared with 52 months (4.3 years) in patients with advanced disease (n74). The MST is pending in the subgroup of patients who were in remission at the start of DDW treatment; only one out of 48 patients died during the cumulative follow-up period of 221.1 years.

Although single DDW treatment was effective, an outstandingly long MST of 24.4 years was attained in the subgroup of 53 patients who were treated with DDW at least twice.

In comparison with published data, DDW treatment in combination with oras, an extension of conventional therapies, noticeably prolonged MST in certain subgroups of breast cancer patients. D-depletion may also be a highly effective therapy for preventing the recurrence.

Deuterium Depleted Water and Cancer Research: Human Case Studies

A retrospective evaluation of the effects of deuterium-depleted water consumption on 4 patients with brain metastases from lung cancer

Krisztina Krempels, et al.

Integr Cancer Ther. 2008 Sep;7(3):172-81

Hypotheses

Because of the number of sufferers and high mortality rate, the standard care and new therapeutic options in the treatment of brain metastasis from lung cancer are the subject of intense research.

A new concept based on the different chemical and physical behaviors of protium and deuterium affecting cell signaling and tumour growth has been introduced in the treatment of cancer patients.

This study aimed to investigate the impact of deuterium-depleted water (DDW) consumption in addition to conventional forms of therapy on the survival of lung cancer patients with brain metastasis.

Study design

A series of 4 case histories was retrospectively evaluated. The patients were diagnosed with brain metastasis deriving from a primary lung tumour and started consuming DDW at the time of or after the diagnosis of the brain metastasis, which was inoperable or the surgical intervention did not result in complete regression. The primary objective was survival.

Methods

The daily water intake of the patients was replaced with DDW, which complemented the conventional forms of treatment. Patients were consuming DDW for at least 3 months. The treatment was continued with DDW of 10 to 15 to 20 ppm lower deuterium (D) content every 1 to 2 months, and thus a gradual decrease was maintained in the D-concentration in the patient’s body.

Results

DDW consumption integrated into conventional treatments resulted in a survival time of 6.6, 54.6, 21.9, and 33.4 months in the 4 patients, respectively. The brain metastasis of 2 patients showed a complete response (CR), whereas a partial response (PR) was detected in 1 patient, and the tumour growth was halted (no change or NC) in 1 case.
The primary tumour of 2 patients indicated CR, and the lung tumour in 2 patients showed PR.

Conclusions

DDW was administered as an oral anticancer agent in addition to conventional therapy and noticeably prolonged the survival time of all 4 lung cancer patients with brain metastasis. We suggest that DDW treatment, when integrated into other forms of cancer treatment, might provide a new therapeutic option.

Soft tissue malignant neoplasms. Clinical case presentation in treatment with deuterium-depleted water

Trăilă Nicola, et al.

1st International Symposium on Deuterium Depletion, 2010, Budapest,
Hungary

Background

Deuterium-depleted water has cellular antiproliferation effects. From experimental works and from clinical experience, it has been established that it has a beneficial effect in the treatment of different types of cancer.

In the Oncological Surgery Department, we gave deuterium-depleted water (DDW) to two types of cancer: advanced rectosigmoid junction cancer and soft tissue sarcomas. Seven patients with superior rectum cancer penetrating in iliac vessels. In these cases, it has been administered intra-arterial chemotherapy by a catheter introduced in the inferior sigmoid artery (superior hemoroidal) and left out under the ribs through a Braun chamber. There have been performed 6 series with 5-Fluorouracil and Calcium folinate. After the intestinal transit had recovered, the DDW was given, 25 ppm, one litre per day. To these patients,a good tolerance for chemotherapy has been discovered, which we have put it on the DDW administration.

We had another case study, a 13-year-old girl who consumed DDW for 5 years (starting from 2005), in a volume of 1 litre per day, 25 ppm. The patient has received 10 series of chemotherapy, according to the 2002 European protocol, for a juvenile rhabdomyosarcoma of the scalp, on the right parietal region. After tumoral ablation, the patient has been given DDW every day so far.

At clinical examination and paraclinical examination, there is no relapse.

Conclusions

For the patients with unrespectable rectosigmoidian cancer, we consider that DDW has decreased the side effects of chemotherapy, has contributed to prolonging life, and has improved the quality of life. For the patient with rabdomiosarcoma the effect of chemotherapy and DDW was spectacular. It is well known the gravity of such malignant tumours, and the fact that the patient is surviving 5 years is a real success.

Deuterium Depleted Water and Cancer Research: In Vivo Studies

Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis

Feng-Song Cong, et al.

Exp. Ther. Med. 2010 Mar-Apr; 1(2): 277–283

Abstract

To investigate the in vivo and in vitro inhibitory effects of deuterium-depleted water (DDW) on human lung cancer and the possible mechanisms underlying these effects, we cultured and treated human lung carcinoma cell line A549 and human embryonic lung fibroblasts HLF-1 with various concentrations of DDW from 2 to 72 h.

Cellular growth inhibition rates were determined using the 3-(4, 5-dimethyldiazol-2-yl)-2, 5- diphenyltetrazolium-bromide) (MTT) proliferation assay. A549 cells were treated with 50±5 ppm DDW, and the morphology and structure of cells were observed by scanning electron microscopy (SEM). We observed alterations in the cellular skeleton by transmission electron microscopy (TEM) and changes in the cell cycle by flow cytometry.

Our data showed that DDW significantly inhibited the proliferation of A549 cells at a specific time point, and cells demonstrated the characteristic morphological changes of apoptosis under SEM and TEM. The length of the S phase increased significantly in cells treated with 50 ppm DDW, whereas the G0 to G1 phase and G2 to M phase were decreased. We observed DDW-induced cellular apoptosis using terminal eoxynucleotidyltransferasedUTP nick end labelling (TUNEL) and DNA fragment analyses. In addition, we established a tumour transplantation model by injecting H460 tumour cells into the subcutaneous tissue of BALB/c mice treated with DDW for 60 days.

We determined the tumour inhibition rate of treated and control groups and found that the tumour weight was significantly decreased, and the tumour inhibition rate was approximately 30% in the DDW group.

We conclude that DDW is a promising new anticancer agent with potential for future clinical application.

Deuterium has a key role in tumour development – a new target in anticancer drug development

G. Somlyai, et al

EJC Supplements 8, No. 5 (2010), 155-225

Abstract

It is known that the deuterium/hydrogen (D/H) mass ratio is the largest of stable isotopes of the same element, causing differences in the physical and chemical behaviour between the two hydrogen isotopes. Although the concentration of D is more than 10 mM in living organisms, the possible role of D had not been investigated for 6 decades after its discovery in the early 30’s.

In order to investigate the possible role of naturally occurring D in living organisms, in cell growth and tumour development, D-depleted water (DDW) was used.The experiments with DDW revealed that due to D-depletion, the cell growth of various cell lines (PC-3 human prostate; Mda, human breast; HT-29, human colon; M14, human melanoma) were inhibited in vitro.

DDW caused tumour regression in xenotransplanted mice (MDA and MCF-7, human breast; PC-3) and induced apoptosis in vitro and in vivo. Deuterium depletion inhibited the expression of certain genes (cmyc, H-ras, COX-2) having key role in tumour development.

Breast tumours in 81 dogs and 14 cats showed a response rate higher than 70%; more than 50% of the pets were cured when DDW was used as a single treatment or in combination with surgery

Deuterium-depleted water effects on Walker tumours

Stefănescu Ioan et al.

National R-D Institute for Cryogenics and Isotopic Technologies – ICIT
Rm. Vâlcea Bulletin UASVM, Veterinary Medicine 65(1)/2008

Abstract

The usual concentration of deuterium in water is about 144 ppm D/(D+H). It is known that the increase of deuterium in the body of living animals is a naturally occurring bioaccumulation process and could be enhanced by adding heavy water, with obviously dramatic changes in health state.

This study aimed to investigate the effect of DDW on experimental Walker tumors inducted at Wistar rats and how it can influence the decrease in deuterium’s value in treated animals.

The result shows that DDW has a significant effect on the subepidermal tumours and it has no side effects. The deuterium’s analysis results show that DDW’s rate of depletion is in correlation with a couple of factors (the concentration of deuterium depleting agent; the period of administration of deuterium depleting agent).

The effect of deuterium-depleted water administration on serum glycoproteins of cytostatics-treated rats

Aneta Pop, et al.

Biotechnological Letters; Vol. 13, No. 6, supplement, 2008, pp. 74-77

Abstract

The current research aimed to investigate the deuterium-depleted water (DDW) effect on animals treated with anticancer drugs Vinblastine, Cyclophosphamide, 5-Fluorouracil and Farmarubicine. Two groups of 10 rats were used for each cytostatic; one group received 60 ppm DDW as a daily diet before, during and after chemotherapy, and the second group received tap water in the same conditions. The other two groups housed in the same conditions received DDW and tap water without any medication.

There were recorded differences in the amount of serum glycoproteins as well as the glycosylation degree and pattern. DDW administration induced a significant decrease of serum total glycoproteins and in the glycosylation degree in all animals, both cytostatics-treated or not. Fucose Raphanus sativus lectin interaction revealed that DDW also induced changes in the glycosylated domain, because it interacted only with the sera from 5-Fluorouracil-treated rats that had not received DDW.

The biological effects of deuterium-depleted water, a possible new tool in cancer therapy

G. Somlyai, et al.

Z. Onkol. / J. of Oncol. 30, 4 (1998)

Abstract

It has been known for decades that due to the mass difference between hydrogen and deuterium, the behaviour of the molecules containing deuterium is altered in chemical reactions. The difference between hydrogen and deuterium concentrations exerts a pronounced influence on the processes taking place in a given biological system. The significant effect of heavy water on the living organism is not a surprise, considering that an important part of the living body consists of water, and heavy water differs from ordinary water in many of its properties.

In order to investigate whether deuterium has any role in living organisms, we applied deuterium-depleted water to prepare a medium for tissue culture and also as drinking water to treat mice xenotransplanted with a human breast tumour.

Naturally occurring deuterium may have a central role in cell signalling

G. Somlyiai, et al.

 Synthesis and applications of
isotopically labelled compounds, 1997

Abstract

It is known that the deuterium/hydrogen (D/H) mass ratio is the largest of stable isotopes of the same element, causing differences in the physical and chemical behaviour between the two isotopes. The experiments carried out so far with D2O in different biological systems and other experiments that revealed the importance of hydrogen bond or intracellular pH in biological processes have neglected the naturally occurring deuterium, in spite of the fact that the concentration of D is about 150 ppm (over 16 mM) in surface water and more than 10 mM in living organisms.

The results revealed that due to D-depletion, the non-tumorous L929 fibroblast cells required a longer time to multiply in vitro, and DDW caused tumour regression in mice. Our recent results suggest that NOD may have a central role either in cell cycle regulations or in apoptosis.

 Naturally occurring deuterium is essential for the normal growth rate of cells

Somlyai G, et al.

Febs Lett. 1993 Feb 8;317(1-2):1-4.

Abstract

In nature, the ratio of deuterium to hydrogen (D/H) is about 1:6600; this means that the natural concentration of D is about 150 ppm (0.015 atom %). A worldwide survey of hydrogen isotopes in precipitation revealed [1,2] that the D content covers a range of 120 and 160 ppm, depending mainly on the site of sampling, and there are several indications that the D/H ratio is not constant in living organisms either [3].

The effect of the replacement of hydrogen with deuterium in biological systems is well documented (e.g. [3,4]); however, the possible role of naturally occurring D in the living organism has never, so far as we are aware, been investigated. The role of naturally occurring D in living organisms has been examined by using deuterium-depleted water (30-40 ppm D) instead of water containing the natural abundance of D (150 ppm). The deuterium-depleted water significantly decreased the growth rate of the L fibroblast cell line, and also inhibited the tumour growth in xenotransplantated mice. Eighty days after transplantation, in 10 (59%) out of 17 tumorous mice, the tumour, after having grown, regressed and then disappeared. We suggest that the naturally occurring D has a central role in signal transduction involved in cell cycle regulation.

Research concerning the radioprotective and immunostimulating effects of deuterium-depleted water

W Bild et al.

Rom J Physiol. 1999 Jul-Dec;36(3-4):205-18.

Abstract

Mice fed for 15 days with Deuterium-Depleted Water (30 ppm deuterium) had a statistically significant increased survival rate compared with control groups fed with normal distilled water (150 ppm deuterium), after 8.5 Gy irradiation (61% survival in the test group versus 25% in the control group).

The hematological picture showed that normal WBC, RBC and platelet counts were maintained in the test groups. Immunological parameters (serum opsonic and bactericidal capacity, bactericidal capacity of the peritoneal macrophages) showed a marked increase in the test groups compared to a severe decrease in the control groups.

Auxiliary tests using chemical radiomimetics (hydrochloric embihine) and immunosuppressors (cyclophosphamide) showed a strong protective effect of deuterium-depleted water against the decrease of the leukocyte counts and other immunologic parameters.

In conditions of experimental inflammation induced with subcutaneously implanted pellets, deuterium-depleted water feeding resulted in a statistically significant increase of the inflammatory response, demonstrated by increased percentages of PMN and lymphocytes in the peripheral blood and the increased phagocytic capacity of the peripheral blood PMN. Experimental infections induced with K. pneumoniae 506 and S. pneumoniae 558 in mice irradiated or treated with cyclophosphamide showed increased, non-specific immunity parameters.

All results show a marked intensification of the immune defences and increased proliferation of the peripheral blood cells, probably accounting for the radioprotective effects.

Deuterium depletion can decrease the expression of C-myc, Ha-ras and p53 genes in carcinogen-treated mice

Z Gyöngyi et al.

In Vivo. 2000 May-Jun;14(3):437-9.

Abstract

In spite of the fact that the deuterium concentration is over 10 mmol/l in all living organisms, its possible role has been ignored for six decades.

Recent studies have shown that the depletion of the naturally occurring deuterium can result in tumour regression in mice, dogs, cats and humans.

The effect of deuterium depletion on gene expression plays a key part in tumour development. The carcinogen, 7,12-dimethylbenz(alpha)anthracene (DMBA), was used to increase gene expression in "short-term" investigations. The expression of c-myc, Ha-ras and p53 genes was followed in CBA/Ca sensitive inbred mice drinking tap water or deuterium-depleted water (DDW) after induction.

By detecting the RNA expression 48 hours after exposure to the carcinogen, it was found that the expression of all genes investigated was inhibited in six different organs (spleen, lung, thymus, kidney, liver and lymph node) in the DDW-treated group.

It is suggested that genes playing a key role in the cell cycle regulation and
tumour development are sensitive to deuterium depletion.

Deuterium Depleted Water and Cancer Research: In Vitro Studies

Deuterium Depleted Water Inhibits the Proliferation of Human MCF7 Breast Cancer Cell Lines by Inducing Cell Cycle Arrest

Kamal Yavaria and Lida Koosheshb

Nutrition and Cancer, 71:6, 1019-1029

ABSTRACT

Recent studies have shown that the depletion of naturally occurring deuterium can result in tumour regression. The present study aimed to show the growth inhibitory effects of DDW discretely and in combination with 5-FU on MCF-7 breast cancer cells and to determine possible mechanisms underlying these changes.

MCF7 cells were grown in RPMI medium with decreasing deuterium concentrations of DDW individually, 5-FU alone and both for 24, 48, and 72 h. Cell viability was determined with the MTT assay. The cell cycle and antioxidant enzyme status were measured using flow cytometry and quantitative luminescence methods, respectively.

Our results showed that treatment with DDW, especially in 30–100 ppm concentrations, imposed the highest cell growth inhibitory effect. The cell cycle analysis revealed that DDW caused the cell cycle arrest in the G1/S transition, reduced the number of cells in the S phase and significantly increased the population of cells in the G1 phase in MCF-7 cells.

The activities of superoxide dismutase (SOD) and catalase (CAT) enzymes also increased in the same low concentrations of DDW.

In conclusion, DDW can open a new strategic approach in breast cancer therapy.

HIGHLIGHTS

• DDW cause lethality in cancer cells.

• DDW augmented 5-FU inhibitory effects on breast cancer cell lines.

• Cell inhibitory results lead to the discovery of synergic effects of DDW–drug combinations

• Synergistic anti-cancer effects of DDW with 5-FU are enhanced by decreasing the deuterium content of the DDW.

• DDW exerts effects on the cell cycle, changes in cell configuration and induces antioxidant enzymes in vitro.

• DDW can be considered as an adjuvant to conventional anticancer agents in future trials.

Deuterium-depleted water (DDW) inhibits the proliferation and migration of nasopharyngeal carcinoma cells in vitro

Hongqian Wang, et al.

Biomedicine & Pharmacotherapy, Volume 67, Issue 6, July 2013, Pages
489-49

Abstract

Recent studies have demonstrated that natural water that has 65% of the deuterium concentration depleted by 65% can exhibit anti-tumour properties. However, the anti-tumour effects of DDW on various nasopharyngeal carcinoma (NPC) cells have not previously been reported.

In the present study, NPC cell lines and normal preosteoblast MC3T3- E1 cells were grown in RPMI1640 media containing different deuterium concentrations (50–150 ppm). The effects of DDW on the proliferation and migration of NPC and MC3T3-E1 cells were investigated using the MTT, plate colony formation, and Transwell assays, as well as Boyden chamber arrays, flow cytometry (FCM), western blot and immunofluorescence.

We found that DDW was an effective inhibitor of NPC cell proliferation, plated colony formation, migration and invasion. In contrast, the growth of normal preosteoblast MC3T3-E1 cells was promoted when they were cultured in the presence of DDW. Cell cycle analysis revealed that DDW caused cell cycle arrest in the G1/S transition, reduced the number of cells in the S phase and significantly increased the population of cells in the G1 phase in NPC cells. Western blot analysis revealed that treatment with DDW significantly increased the expression of NADPH: quinone oxidoreductase-1 (NQO1), while immunofluorescence assay analysis revealed that treatment with DDW decreased the expression of PCNA and matrix metalloproteinase 9 (MMP9) in NPC cells.

These results demonstrated that DDW is a novel, non-toxic adjuvant therapeutic agent that suppresses NPC cell proliferation, migration, and invasion by inducing the expression of NQO1 and causing cell cycle arrest, as well as decreasing PCNA and MMP9 expression.

Research progress of the inhibitory effect of deuterium-depleted water on cancers

Nan Fang Yi Ke Da Xue Xue Bao. 2012 Oct;32(10):1454-6. (Article in
Chinese)Wang H, Liu C, Fang W, Yang H.

Sino-America Cancer Research Institute, Guangdong Medical College,
Dongguan, China.

Abstract

Deuterium is an important predisposing factor for cancer. Deuterium-depleted Water, also known as low deuterium water, ultra-light water or no deuterium water, can be obtained by removing deuterium from natural water. Studies have shown that water with a low deuterium concentration (<65% percent of volume) can inhibit cancer growth. Clinical trials demonstrated that drinking DDW (10-20 ppm) caused growth arrest of malignant cells in cancer patients and significantly prolonged the patients' survival, with improved quality of life. A wide range of anti-cancer drugs in current use are associated with severe adverse effects, while deuterium-depleted water appears to have virtually no pharmacological side effects and is convenient to administer.

The authors review the advances in the research on anti-cancer effects and the underlying mechanisms of deuterium-depleted water.

Submolecular regulation of cell transformation by deuterium-depleting water exchange reactions in the tricarboxylic acid substrate cycle

Laszlo G Boros et al.

Medical Hypotheses, Volume 87, February 2016, Pages 69-74

Abstract

The naturally occurring isotope of hydrogen (1H), deuterium (2H), could have an important biological role. Deuterium-depleted water delays tumour progression in mice, dogs, cats and humans. Hydratase enzymes of the tricarboxylic acid (TCA) cycle control cell growth and deplete deuterium from redox cofactors, fatty acids and DNA, which undergo hydride ion and hydrogen atom transfer reactions.

A model is proposed that emphasises the terminal complex of the mitochondrial electron transport chain, reducing molecular oxygen to deuterium-depleted water (DDW); this affects gluconeogenesis as well as fatty acid oxidation. In the former, the DDW is thought to diminish the deuteration of sugar-phosphates in the DNA backbone, helping to preserve stability of hydrogen bond networks, possibly protecting against aneuploidy and resisting strand breaks, occurring upon exposure to radiation and certain anticancer chemotherapeutics.

DDW is proposed here to link cancer prevention and treatment using natural ketogenic diets, low deuterium drinking water, as well as DDW production as the mitochondrial downstream mechanism of targeted anti-cancer drugs such as Avastin and Glivec. The role of 2H in biology is a potential missing link to the elusive cancer puzzle, seemingly correlated with cancer epidemiology in Western populations as a result of excessive 2H loading from processed carbohydrate intake in place of natural fat consumption.

Anticancer Effect of Deuterium Depleted Water - Redox Disbalance Leads to Oxidative Stress

Xuepei Zhang et al.

Mol Cell Proteomics. 2019 Dec;18(12):2373-2387

Abstract

Despite the convincing empirical evidence that deuterium-depleted water (DDW, 25-125 ppm deuterium) has an anticancer effect, the molecular mechanism remains unclear.

Here, redox proteomics investigation of the DDW action in A549 cells revealed an increased level of oxidative stress, whereas expression proteomics in combination with thermal profiling uncovered a crucial role of mitochondrial proteins.

In the proposed scenario, reversal of the normally positive deuterium gradient across the inner membrane leads to an increased export of protons from the matrix to intermembrane space and an increase in the mitochondrial membrane potential, enhancing the production of reactive oxygen species (ROS).

The resulting oxidative stress leads to slower growth and can induce apoptosis. However, further deuterium depletion in ambient water triggers a feedback mechanism, which leads to restoration of the redox equilibrium and resumed growth.

The DDW-induced oxidative stress, verified by traditional biochemical assays, may be helpful as an adjuvant to ROS-inducing anticancer therapy.

DDWand Diabetes and other Metabolic issues Research

Influence of deuterium-depleted water on indicators of prooxidant-antioxidant and detoxifying systems in experimental diabetes.

Endocrine Abstracts (2015) 38 P290 | DOI:10.1530/endoabs.38.P290 Stepan Dzhimak, Alexander Basov, Lilia Fedulova & Elena Kotenkova

Abstract

Studying the effect of deuterium depleted water (DDW) on isotope (D/H) composition and condition of an antioxidant-prooxidant plasma and lyophilized tissues of internal organs (liver, kidney) balance appropriate indicators in rats were compared: in group 1 (n=15) consumed mineralized water (150 ppm), which by a single intraperitoneal injection of alloxan (at a dose of 17 mg/100 g body weight) was established experimental model of diabetes; group 2 (n=15) consumed mineralized water (40 ppm) for 30 days before creation of a similar model of experimental diabetes.

On day 5 after modelling of alloxan diabetes in rats of both groups, an increase in blood glucose level by 2.2 times, an increase in the activity of enzymes (aspartate aminotransferase, alanine aminotransferase), characterising cytolytic processes, increasing concentrations of creatinine, bilirubin and urea.

It was found that in group 2, after 45 days of drinking 40 ppm water, the deuterium content in the bloodplasma was reduced to 99.7±0.4 ppm (P<0.05), which was on 34.1% lower in comparison withGroup 1 (P<0.05). In addition, the integral index of the functioning of the low molecular unitprooxidant-antioxidant blood system (COMBer – patent number 2236008 RU) in group 1 was17.9% higher than in group 2 (P<0,05), indicating that the perspective of DDW using at thecomplex correction of metabolic disorders in the antioxidant system, observed during thedevelopment of diabetes.

Also observed a decrease in the concentration of endogenous toxic substances in theblood of rats from group 2, which was confirmed by lower (on 27.1%, P<0.05) integralindex values of endogenous intoxication in group 2 (94.2% hypercatabolism) comparedwith the group 1 (129.3% hypercatabolism), that indicating on increased functionalactivity of detoxifying system and increasing of nonspecific organism resistance whenDDW administered in the rats diet.

Decreasing of Deuterium Concentration of Water: A Possible Tool in Diabetes Therapy

Kamal Yavari et al.

Electronic Journal of Biology, 2017, Vol. 13(4): 314-319

Abstract

Developing new diabetes care agents is of great importance and incites increasing demand for new products to improve diabetes care. Several compounds have been made and investigated for this purpose.

DDW is a type of water that has several health benefits and has been used for medicinal purposes in recent years. This study aims to test the effect of removal of D2 O on the glucose metabolism in sreptozotocin (STZ)-induced diabetic rat model and to explore the possible mechanism.

Methods: Diabetes was induced by a single i.p. injection of 60 mg/kg body weight of STZ. After 2 weeks, animals were randomly distributed into several groups to test the effect of D2O (25-150 ppm) on glucose metabolism in diabetic animals with or without insulin treatment. The serum glucose and HbA1C parameters were tested, and at the end of 8 weeks of intervention, the expression of membrane-associated GLUT-4 mRNA was detected by semi-quantitative RT-PCR. Results:

Our results indicate that STZ treatment significantly increased serum glucose and HbA1c. Depletion of D2O has a minor influence on the measured parameters in animals that have not received insulin. However, the measured parameters were significantly lower in those animals that received lower D2O-containing drinking water and insulin treatment. The membrane-associated GLUT-4 was significantly higher in these animals also.

Conclusions: These data suggest that D2 O depletion enhances insulin effect on GLUT-4 translocation and potentiates glucose uptake in diabetic animals, providing good evidence for its potential use in diabetes care.

Correction of metabolic processes in rats during chronic endotoxicosis using isotope (D/H) exchange reactions

S.S. Dzhimak, et al.

Animal And Human Physiology Biology Bulletin June 2015, Volume 42, Issue
5, pp 440-448

Abstract

The effect of isotope exchange reactions (deuterium/protium, D/H) on morphofunctional indices and the state of the antioxidant blood system in rats was studied under physiological conditions and during experimental chronic endotoxicosis of hepatorenal genesis. It was demonstrated that the introduction of water with a decreased content of deuterium in the food rations of rats results in a decrease in its concentration in the blood plasma by 32–36% (to 98–106 ppm) and in lyophilised liver, kidney, and heart tissues by 13–17% (to 123–128 ppm). It was noted that it is accompanied by correction of metabolic processes, an increase in the functional activity of the nonspecific protection system, and an increase in the body weight growth by the 42nd day in the group of animals that passed (for 14 days) the stage of preliminary adaptation with a change in the D/H ratio in the organism.

Deuterium Depleted Water and Mental Health Research

Deuterium content of water increases depression susceptibility: The potential role of a serotonin-related mechanism

Tatyana Strekalova et al.

Behavioural Brain Research, Volume 277, 15 January 2015, Pages 237–244

Highlights:

• Geographical distribution of deuterium correlates with depression rate.

• Deuterium-depleted water reduces stress-induced depressive-like signs in mice.

• Hippocampal proliferation after stress is rescued by deuterium-depleted water.

• Deuterium-depleted water induces SSRI-like changes in EEG parameters of sleep.

• The above-indicated effects may be due to normalization of hippocampal 5-HTT level.

Abstract

Environmental factors can significantly affect disease prevalence, including neuropsychiatric disorders such as depression. The ratio of deuterium to protium in water shows substantial geographical variation, which could affect disease susceptibility. Thus, the link between deuterium content of water and depression was investigated, both epidemiologically and in a mouse model of chronic mild stress. We performed a correlation analysis between the deuterium content of tap water and rates of depression in regions of the USA.

Next, we used a 10-day chronic stress paradigm to test whether 2-week deuterium-depleted water treatment (91 ppm) affects depressive like behavior and hippocampal structure. The effect of deuterium depletion on sleep electrophysiology was also evaluated in naïve mice.

There was a geographic correlation between the content of deuterium and the prevalence of depression across the USA. In the chronic stress model, depressive-like features were reduced in mice fed with deuterium-depleted water, and SERT expression was decreased in mice treated with deuterium-treated water compared with regular water. Five days of predator stress also suppressed proliferation in the dentate gyrus; this effect was attenuated in mice fed with deuterium-depleted water. Finally, in naïve mice, deuterium-depleted water treatment increased EEG indices of wakefulness and decreased duration of REM sleep, phenomena that have been shown to result from the administration of selective serotonin reuptake inhibitors (SSRI).

Our data suggest that the deuterium content of water may influence the incidence of affective disorder-related pathophysiology and major depression, which might be mediated by the serotonergic mechanisms. © 2014 Published by Elsevier B.V.

Deuterium Depleted Water and Memory Research

Deuterium-depleted water has stimulating effects on long-term memory in rats

Cristian Mladina  et al.

Neuroscience Letters, Volume 583, 7 November 2014, Pages 154–158

Abstract

Deuterium-depleted water (DDW) is a water that has a 6–7-fold lower concentration of the naturally occurring deuterium (20–25 ppm vs. 150 ppm). While administered for a longer period, it may reduce the concentration of deuterium throughout the body, thus activating cellular mechanisms which are depending on protons (channels, pumps, enzyme proteins).

The present work aimed to study, for the first time in our knowledge, the possible influence of deuterium-depleted water (DDW) chronic administration in normal Wistar rats, as compared to a control group which received distilled water, on spatial working memory and the locomotor activity (as studied through Y-maze) or both short-term and long-term spatial memory (assed in radial 8 arms-maze task).

Our results presented here showed no significant modifications in terms of spatial working memory (assessed through spontaneous alternation percentage) and locomotor activity (expressed through the number of arm entries) in the Y-maze, as a result of DDW ingestion. Also, no significant differences between the DDW and control group were found in terms of the number of working memory errors in the eight-arm radial maze, as a parameter of short-term memory.

Still, we observed a significant decrease in the number of reference memory errors in the DDW rats. In this way, we could speculate that the administration of DDW may generate an improvement in the reference memory, as an index of long-term memory.

Thus, we can reach the conclusion that the change between the deuterium/hydrogen balance may have important consequences for the mechanisms that govern long-term memory, as shown here, especially in the behavioural parameters from the eight-arm radial maze task.

Deuterium Depleted Water and the Detoxification of Heavy Metals Research

Variation of the deuterium concentration in rats’ blood after deuterium-depleted water administration and intoxication with cadmium

Petcu Mihaela Doina, et al.

Bulletin UASVM, Veterinary Medicine 65(1)/2008

Abstract

The effects of cadmium pollution are highlighted in many studies [7,14]. Cadmium, absorbed within the organism, inhibits the action of some antioxidant enzymes, especially those that contain SH and affect the liver and kidneys. The level of deuterium in tap water is 150 ppm, and in deuterium-depleted water is under 80 ppm. Deuterium-depleted water with a deuterium level of 30 ppm has an antioxidant effect on the organism [9, 10].

The present study has assessed the effects of deuterium-depleted water (30 ppm) on the deuterium blood level in rats exposed to cadmium (20 ppm Cd/kg administered as CdCl2 solution in a single dose).

The intoxication with cadmium modified the blood level of deuterium in the animals and the kidney, liver and spleen weight. The blood level of deuterium was determined through weight spectroscopy with the spectrophotometer SMAD1.

We observed a protective effect of deuterium-depleted water on the rat organism for preventive administration as well as treatment and the important role in eliminating cadmium.

The Influence of Deuterium Depleted Water on the Hematocrit and the Leukocyte Formula in Rats Intoxicated With Chromium

Cărpinişan L. et. al.

Animal Science and Biotechnologies, 2010, 43 (1) 464

Abstract

The aim of this study was to emphasise the influence of the deuterium-depleted water in the chromium (K2Cr2O7) single dose intoxication.

The haematocrit and the leukocyte formula were determined, following the chrome intoxication in rats divided into 8 batches comprising 6 individuals each. The blood samples were collected directly from the heart (intracardiac punction) under narcosis. The data were processed statistically by means of the Kruskal-Wallis and Mann-Whitney tests, MINITAB 15 and SPSS 17 Software.

The haematocrit was improved, and the nonspecific defence realised by the neutrophils was stimulated constantly after the deuterium-depleted water administration.

Anti-aging effects of deuterium depletion on Mn-induced toxicity in a C. elegans model

Daiana Silva Ávilaa, et al.

Toxicol Lett. 2012 Jun 20;211(3):319-24, Epub 2012, Apr 26

Abstract

Work with sub-natural levels of deuterium (D) in animals has demonstrated an anticancer effect of low D-concentration in water.

Our objective was to investigate whether deuterium-depleted water (DDW) can overturn reverse manganese (Mn)-induced reduction in life span, using the Caenorhabditis elegans (C. elegans) as a model system.

DDW per se had no effect on worms’ life span 48 h after treatment; however, it reversed the Mn-induced decrease in C. elegans life span. Mn reduced DAF-16 levels, a transcription factor strongly associated with life-span regulation.

Low Dconcentration (90 ppm) restored the Mn-induced changes in DAF-16 to levels indistinguishable from controls, suggesting DDW can regulate the DAF-16 pathway. We further show that insulin-like receptor DAF-2 levels were unaltered by Mn exposure, tAKT levels increased, whilst superoxide dismutase (SOD-3) levels were decreased by Mn. DDW (90 ppm) restored the levels of tAKT and superoxide dismutase (SOD) to control values without changing DAF-2 levels.

Treatment of Mn-exposed worms with DDW (90 ppm) restored life-span, DAF-16 and SOD-3 levels to control levels, strongly suggesting that low D concentrations can protect against Mn toxic effects.

Deuterium Depleted Water and the Immune System

Deuterium research concerning the physiological effects of deuterium-depleted water on nonspecific immunity

Haulica Ion et al.

Rom J Physiol. 1999 Jul-Dec;36(3-4):205-18.

Abstract

In this research, the effect of deuterium-depleted water on Swiss mice was studied to improve their capacity to influence the immunity.
to improve their capacity to influence the immunity.

Results:

1. In animals with normal IS, deuterium-depleted water stimulated nonspecific immunity (increase in the percentage of PMN and lymphocytes, increase in the value of the NBT-test);

2. In animals with experimental infections, deuterium-depleted water stimulation of immunity defence was stronger;

3. At the same time, deuterium-depleted water didn’t modify the parameter of specific immunity.

Deuterium Depleted Waters affect on Plants and Bacteria

Studying the Isotopic Effects of Deuterium in Biological Objects

Oleg Mosin si Ignat Ignatov

European Reviews of Chemical Research, 2015, Vol.  (3), Is

Abstract

This article describes the data on isotopic effects of deuterium in various biological objects, such as the cells of methylotrophic, chemoheterotrophic, photoorganotrophic microorganisms, green algae, and animal cells.

It was demonstrated that the increased content of deuterium in water leads to physiological, morphological and cytological alterations of the cell, and also renders a negative influence on cellular metabolism, while deuterium-depleted water (DDW) with decreased deuterium content of 20–30 % exerts beneficial effects on the organism. The maximum kinetic isotopic effect measured at ordinary temperatures in chemical reactions leading to rupture of bonds involving hydrogen and deuterium lies in the range kH/kD = 6–8 for C–H versus C–D, N–D versus N–D, and O–H versus O–D-bonds. By the IR-spectroscopy method, water samples with varying content of deuterium were investigated.

HISTO-ANATOMICAL ASPECTS IN MAIZE (ZEA MAYS L.) SEEDLINGS DEVELOPING UNDER THE INFLUENCE OF DEUTERIUM DEPLETED WATER

Corneliu TĂNASE1 et al.

AnaleleŞtiinţifice ale Universităţii „Al. I. Cuza” Iaşi, s. II a.
Biologievegetală, 2014, 60, 2: 5-10

Abstract

The paper presents histo-anatomical aspects, evidenced in seedlings of maize (Zea mays L.) grown under the influence of deuterium-depleted water (DDW). The aim of this study was to identify the internal structure changes in maize seedlings that resulted in this case.

For histo-anatomical characterisation, the vegetal material was fixed and preserved, and then cut by hand microtome with a botanical razor. The sections obtained were stained using double staining reagents.

As compared with the control sample, it was observed that deuterium-depleted water determines a better development of the absorbent bristles and increases the number of leading bundles and central vessels in metaxilem.

Deuterium Depleted Water and Aging

EFFECT OF DEUTERIUM-DEPLETED WATER ON NORMAL HUMAN SKIN CELLS IN CULTURE AND 3D SKIN EQUIVALENT

ShanShanJIANGa, et al.

a. JALA Research, 333 Guiping Road, Shanghai, 200233, China.

b. School of Life Sciences and Biotechnology, Shanghai Jiao Tong
University, Shanghai 200240, P.R. China.

Corresponding author: DanDan JIANG, JALA Research Centre, Fundamental
Research Department, 333 Guiping Road, Xuhui, Shanghai 200233, P.R. China,

CONCLUSION

The results showed that DDW treatment significantly accelerated the reconstruction of both epidermal and dermal compartments in the 3D skin equivalent. The epidermis appeared thicker and well-differentiated, however the untreated control (UPW) showed a thin and poorly organised structure.

At the same time, DDW stimulated the synthesis of the ECM at the dermal level. Histological and immunohistological analysis confirmed the accelerated epidermal and dermal maturation and showed a significant increase of Ki-67 proliferation and filaggrin differentiation epidermal markers and a significant stimulation of extracellular matrix protein deposition, such as collagen I, hyaluronan and elastin.

Concomitantly, DDW induced a higher expression of basement membrane proteins associated with re-epithelisation, such as laminin 332.

These results demonstrate the influence of DDW on skin cell proliferation, differentiation, and extracellular matrix synthesis in a 3D full-thickness skin equivalent model, and further support the importance of DDW in cosmetic applications.

The role of deuterium in DNA degradation

Kirk Goodall

The Official Newsletter of the American Academy of Anti-Aging Medicine,
Fall 2003

Introduction

Evidence indicates that aging is coupled to an accumulation of errors in DNA that arise due to strand breakage, DNA replication errors, or dysfunctional DNA repair mechanisms. Naturally occurring background radiation is a pervasive mutagen known to adversely affect DNA.

Deuterium oxide is also pervasive and adversely affects DNA. As a consequence and over time, through the mechanism of increased hydrogen bonding strength, deuterium may disrupt DNA repair enzymes and slow the rate of DNA replication, exposing it to a greater chance of corruption. The maximum lifespan that an organism can achieve is tied to its DNA. DNA is damaged by free radicals produced by radiation, mutagens, and normal metabolic processes.

Concluding remarks

Deuterium-depleted water (DDW) does not change its chemical composition when digested and has a direct effect at the cellular level. Consumption of DDW can conceivably protect DNA from damage and assist DNA repair mechanisms, but it does not directly repair DNA. It remains undetermined, given present scientific knowledge, whether DDW consumption will “rejuvenate” the body, but it may become a new therapeutic approach or intervention that may assist in protecting cells and tissues of the body, enabling them to function more efficiently.

The author hopes that future studies comparing deuterium in the drinking waters of inhabited and developed environments versus that of less developed and sparsely populated locations will elucidate a mechanism for DNA damage and its prevention or reversal.

The Neuroprotective Effects of DDW

Neuroprotective Effects of Deuterium‑Depleted Water (DDW) Against H2O2‑Induced Oxidative Stress in Differentiated PC12 Cells Through the PI3K/Akt Signalling Pathway

Yongfu Wu et al.

Neurochemical Research (2020) 45:1034–1044

Abstract

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Induction of endogenous antioxidants to act against oxidative stress-mediated neuronal damage seems to be a reasonable strategy for delaying the progression of such diseases.

In this study, we investigated the neuroprotective effect of deuterium-depleted water (DDW) against H2O2-induced oxidative stress in differentiated PC12 cells and the possible signalling pathways involved. The differentiated PC12 cell line was pretreated with DDW containing different concentrations (50–100 ppm) of deuterium and then treated with H2O2 to induce oxidative stress and neurotoxicity.

We assessed cell survival, reactive oxygen species (ROS) generation, TUNEL assay, catalase (CAT), copper and zinc-containing superoxide dismutase (CuZn-SOD) and superoxide dismutase (SOD) activity and performed Western blot analysis to investigate the neuroprotective effect of DDW.

The results indicated that DDW could attenuate H2O2-induced apoptosis, reduce ROS formation, and increase CAT, CuZn-SOD and SOD activity in H2O2-treated PC12 cells. Western blot analysis revealed that DDW treatment significantly increased the expression of p-Akt, Bcl-2 and GSK-3β. However, the protective effect of DDW on cell survival and the DDW-mediated increases in p-Akt, Bcl-2 and GSK-3β were abolished by pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002.

In summary, DDW may protect differentiated PC12 cells against H2O2-induced oxidative stress through the PI3K/Akt signalling pathway.

Potential Use of Deuterium-Depleted Water in Interplanetary Travel

Possibility of deuterium-free water as an antitumoral means with reference to conditions of the Martian expedition

Sinyak, Y. et al.

34th COSPAR Scientific Assembly, The Second World Space Congress, held
10-19 October 2002 in Houston, TX, USA, meeting abstract

Abstract

The interplanetary space flights, the Martian program as an example, will take place under conditions of increasing radiation levels for the crew. The search for methods for a decrease of oncologic risk produced by irradiation of astronauts is one of the major factors for the successful implementation of a flight program.

One of such methods is the usage by the crew of potable water with the reduced concentrations of a heavy stable isotope of hydrogen - deuterium, which can be obtained in the regenerative life support systems. The heavy water (D2O) has toxic properties, distorting biochemical reactions in the cell, inhibiting the process of DNA replication. It can be presumed that the replacement of deuterium in the water will result in normalisation of cell metabolism, reparation will take place, and this will lead to the inhibition of tumour development.

In this study, the water with a decreased by 65% of deuterium was used. Antitumor properties of D2-free water were studied with transplantable Lewis lung carcinoma in the BDF1 strain of mice.

First results show that the average time of appearance of the first nodules at the site of transplantation was 14 % longer in mice fed D2-free water as compared to controls. The tumour volume in the experimental group (decreased content of D2) was always lower than in the control. Statistically significant differences in the tumour volume were registered at the 13, 15, 23, 26 and 28 -th days after transplantation. Inhibition of tumour growth was equal to 100% and 51% at the 5-th and 15-th days after transplantation, respectively. Increase of life span in the experimental group was 10%.

The results indicate that the use by astronauts of water with decreased content of deuterium may decrease the risk of oncological diseases under conditions of high radiation levels in the flight to Mars.

Other DDW Research

Local Exremum at 8.95 μm in the Spectrum of Mountain Water as an indicator for Health and Longevity

Ignat Ignatov et al.

Journal of Health, Medicine and Nursing, ISSN 2422-8419 (Online), Vol.
10, 2015

Abstract

In this paper, data on longevity factors and mountain water in a factorial research of phenomenon of longevity in mountainous and field areas of Bulgaria. The dependence was established among various internal and external factors on a phenomenon of longevity – residence area, health status, gender and heredity.

It was shown that water is among the most important factors for longevity. Natural waters derived from various Bulgarian water springs were investigated by IR-spectroscopy, NES-, and DNES methods.

It was shown that the increased content of deuterium leads to physiological, morphological and cytological alterations of the cell, and also renders a negative influence on cellular metabolism, while deuterium-depleted water with decreased deuterium content of 20-30% has beneficial effects on health.

Using IR-spectroscopy (NES and DENS-method), various samples of water with varying contents of deuterium, received from Bulgarian water springs, and the blood serum of cancer patients as well. As the estimation factor was measured, the values of the average energy of hydrogen bonds (ΔEH...O) among H2O molecules, as well as local maxima in the IR spectra of various samples of water and human blood serum at -0.1387 eV and wavelength – 8.95 μm.

For a group of people in critical condition of life and patients with malignant tumors the greatest values of local maxima in IR-spectra are shifted to lower energies relative to the control group. The obtained results testify to the necessity of the consumption of clean natural water whose quality satisfies the standards of mountain water from Bulgarian water springs.

Conclusion

Research conducted by us shows that the direct relationship of man and nature – clean air, natural food from eco-farms and physical activity explains the difference between the larger number of centenarians who live in the mountain regions of Bulgaria and Russia and their high average number.

Natural water with decreased content of deuterium seems to be one of the most important factors for longevity. In Bulgaria, most centenarians live in the Rhodope Mountains, while in Russia, in Dagestan and Yakutia.

Deuterium-Depleted Water as an Adjuvant Therapeutic Agent for the Treatment of Diet-Induced Obesity in Rats

Tetiana Halenova et al.

Molecules 2020, 25, 23 Abstract

In this study, we present the potential application of deuterium-depleted water (DDW) for the prevention and adjuvant treatment of obesity in rats. We tested the hypothesis that DDW can alleviate diet-induced obesity (DIO) and its associated metabolic impairments.

Rats fed a high-fat diet had an increased body weight index (BWI), glucose concentration, and level of certain proinflammatory cytokines; decreased levels of insulin in the serum; decreased tryptophan and serotonin in the brain, and a decreased concentration of some heavy metals in the liver.

Drinking DDW at a concentration of 10 ppm deuterium/protium (D/H) ad libitum for 3 weeks restored the BWI, glucose (serum), tryptophan (brain), and serotonin (brain) levels and concentration of Zn in the liver in the DIO animals to those of the controls. The levels of proinflammatory cytokines (IL-1β, IL-6, IFNγ) and anti-inflammatory TNFα were decreased in DIO rats, while anti-inflammatory cytokine (IL-4, IL-10) levels remained at the control levels, which is indicative of a pathophysiological syndrome.

In contrast, in groups of rats treated with DDW, a significant increase in anti-inflammatory (IL-4, IL-10) and proinflammatory cytokines (IFNγ) was observed.

This finding indicates a reduction in systemic inflammation in obese animals treated with DDW. Similarly, the high-fat diet caused an increased level of oxidative stress products, which was accompanied by decreased activity of both superoxide dismutase and catalase, whereas the administration of DDW decreased the level of oxidative stress and enhanced antioxidant enzyme activities.

In Vitro Study of Deuterium Effect on Biological Properties of Human Cultured Adipose-Derived Stem Cells

Alona Zlatska et al.

Hindawi The Scientific World Journal Volume 2018, Article ID 5454367, 10
pages

Abstract

In the current in vitro study, we have shown the impact of deuterium content in the growth medium on the proliferation rate of human cultured adipose-derived stem cells (ADSC). ADSCs have also demonstrated morphological changes when cultured in deuterated growth medium: the cell cultures did not reach confluence but acquired polygonal morphology with pronounced stress fibres. At high deuterium concentrations, the ADSCs population doubling time increased, which indicated the cell cycle retardation and decrease of cell proliferation rate.

The deuterated and deuterium-depleted growth media demonstrated acute and chronic cytotoxicity, respectively.The minimal migration ability was observed in the deuterated medium, whereas the highest migration activity was observed in the medium with the deuterium content close to natural. The cells in the deuterated growth medium demonstrated a decrease in metabolic activity after three days in culture. In contrast, in deuterium-depleted medium, there was an increase in ADSC metabolic activity.

Influence of Deuterium Depleted Water on Rat Physiology: Reproductive
Function, Forming and Posterity Development.


Lilia V. et al.

Life Science, Vol 6, No. 2(2016)

Abstract

Reproductive function and postnatal progeny development of rats in four generations treated with deuterium-depleted water (40 ppm) were investigated. The targeted generations were parents (F0), first (F1), second (F2) and third (F3). Replacement of tap water with deuterium-depleted water did not influence the fertility index, survival and postnatal offspring development. Reproductive function, physical parameters, and reflexes development in rats and pups consumed DDW were similar or more intensive in comparison with the control group. Therefore, DDW consumption did not possess any toxic effects and may enhance general postnatal development.

Hepatoprotective Effects of Deuterium Depleted Water (DDW) Adjuvant with Saturejarechingeri Essential Oils

Faezeh Fatemi1, et al.

Nuclear Fuel Cycle Research School, Nuclear Science and Technology
Research Institute, Tehran, Iran, etc.

Abstract

This study was carried out to investigate the hepatoprotective effect of deuterium-depleted water (DDW) with and without Saturejarechingeri essential oil (E.O) mixture on paracetamol-induced hepatotoxicity in rats. The animals were divided into 24 groups (n=5): The negative control group used tap water for 14 days following DMSO i.p injection on day 15th. The control group received tap water in 14 days following 500 mg/kg b.w.i.p injection of acetaminophen dissolved in DMSO.

The treatment groups received only DDW (30 and 60 ppm) for 14 days, concomitant with treatment groups receiving DDW plus i.p injection of S. rechingeri oil following acetaminophen injection on day 15th. Indeed, hepatoprotective activity was evaluated by the biochemical estimation of acetaminophen metabolism enzymes, cytochrome P450 (CYP450), glutathione s-transferase (GST), together with the level of glutathione (GSH). The markers of liver injuries (ALT, AST, and ALP) were also estimated in plasma.

The results indicated that administration of DDW and DDW+E.O resulted in liver damage compensation as manifested by a significant decrease in the activities of CYP450 and AST, as well as significantly elevating the levels of GSH and GST. The present study reveals that the DDW could afford a significant protection against paracetamol‐ induced hepatocellular injuries

Anti-inflammatory Effects of Deuterium-Depleted Water Plus Rosa Damascena Mill. Essential Oil Via Cyclooxygenase-2 Pathway in Rats

Faezeh FATEMI

Turk J Pharm Sci 2020;17(1):99-107

Abstract

Objectives: Natural medicine has been proposed for treating sepsis worldwide. Therefore, in this study, the effect of deuterium-depleted water (DDW) alone and adjuvant with Rosa damascena Mill. (RD) essential oils was considered through the evaluation of oxidative stress-antioxidant parameters and the expression of cyclooxygenase-2 (COX-2) inflammatory gene in liver damage caused by sepsis.

Materials and Methods: The rats were randomly divided into 5 groups: 1) laparotomy group; 2) cecal ligation and puncture (CLP) group; 3) DDW (15 ppm and 30 ppm doses) group; 4) DDW (15 ppm and 30 ppm doses) plus RD essential oil (100 mg/kg.bw); 5) indomethacin (2 mg/kg.bw) as a positive control. The treatments were daily for 2 weeks, and the CLP model was created on day 15. Then, the animals were killed, and their liver tissue was separated for histopathologic and biochemical assessment.

Results: Our results demonstrated that the treatment of animals with DDW and DDW plus RD essential oil was effective due to the regulation of the oxidative stress-antioxidant parameters including lipid peroxidation, glutathione (GSH), GSH s-transferases, myeloperoxidase, ferric reducing ability of plasma and inflammatory parameters such as prostaglandin E2 and COX-2. Pathological studies also showed that sepsis led to liver tissue injuries, which can be reduced by treatments.

Conclusion: Sepsis caused oxidative stress in the liver tissue, but the administration of DDW and DDW plus RD essential oil can be useful to prevent and heal these injuries.

THE RADIOPROTECTIVE EFFECT OF DEUTERIUM DEPLETED WATER AND POLYPHENOLS

Gabriel C. Corneanu et al.

Environmental Engineering and Management Journal, November 2010, Vol. 9, No. 11, 1509-1514

Abstract

In the experiments performed in the mouse (Mus musculus), the radioprotective effect of Deuterium Depleted Water (DDW, with 30ppm deuterium) and a 0.01% total extract of polyphenols (from Aralia mandshurica cortex), applied individually or together, was tested, towards a sublethal dose of X-rays (5.28 Gy).

The animals were intraperitoneally injected (five injections with 0.5 mL each, one at two days) with single DDW, or with a 0.01% polyphenols diluted in DDW. The stress factor was applied one day after the third injection. As a radiobiological point, the ultrastructural features of the liver were used (following the animal sacrifice a day after the last injection).

The X-irradiation of the animals treated independently or combined with DDW and polyphenol extract manifests a radioprotective effect, especially in the combined action of the two factors. Also, it was established that the application of a single exogenous factor enhanced the lipid drops from hepatocytes.

Patents using Deuterium Depleted Water

Deuterium Depleted Water (DDW) Using As Adjuvant In Cancer Therapy ForCytostatics Toxicity Reducing

Inventors: Nicolae Manolescu, et al.

Publication date: 2008-09-04; Patent application number: 20080213390

Abstract

A method is provided for utilising Deuterium Depleted Water (DDW) as an adjuvant in cancer therapy and for reducing cytostatic toxicity. The method includes the administration of DDW having a concentration of about 60 ppm as a daily diet to animals.

The cancer therapy can include a mono-chemotherapy where a single drug or cytostatic is used or a poly-chemotherapy where more than one drug or cytostatic is used. The drugs or cytostatics that are used for chemotherapy can include one or more of Cyclophosphamide, 5-Fluorouracil, Farmarubicin, and Vinblastine. The method can be used to treat different types of cancer.

3. A method of utilizing deuterium depleted water for the manufacture of a medicament for reducing the toxicity of cytostatics by administering water having a 60 ppm concentration, before, during and after mono-chemotherapy with at least one of cyclophosphamide, 5-fluorouracil, farmarubicine and vinblastine, as a daily diet.

4. A method of utilizing of deuterium depleted water for the manufacture of a medicament for reducing the toxicity of cytostatics by administering water having a 60 ppm concentration, before, during and after poly-chemotherapy with at least one of cyclophosphamide, 5-fluorouracil, vincristine and vinblastine, as a daily diet.

5. A method of treating an organism having cancer comprising administering deuterium-depleted water, before, during and after chemotherapy, as a daily diet.

Results All of these studies and examinations show post-therapeutically improvement of the immune system of these animals receiving 60 DDW and cytostatics, and therefore, their therapeutic remission is extended. All of these beneficial effects provide better protection against cytostatic toxicity. Thus, a better therapeutic index was obtained, which results in the prolongation of pets' lives and a remarkable improvement in the comfort of these animals that have different types of cancers.

The results obtained from the studies of the dogs confirm the results obtained from the studies of the rats, and show that 60 ppm DDW has certain properties for cancer organism detoxification, or for an organism that is subjected to the toxic stress generated by cytostatics (i.e., negative side effects), which are used in anti-cancer polychemotherapy. Thus, 60 DDW can be used as an effective adjuvant in reducing the toxicity of cytostatics that are used in cancer polychemotherapy, for all organisms, including humans and pets.