Positive Health Online

Deuterium- depletion is a new complementary modality in oncotherapy and prevention; the method can be safely applied in addition to conventional treatments and as an extension of those. Replacement of the daily fluid intake of patients with deuterium depleted water (DDW) results in the shortage of deuterium (D) in the body, and might exert an anticancer effect.

Hydrogen has a naturally occurring isotope, deuterium, which is present in surface waters and also in living organisms. The twofold difference in the atomic mass of the two isotopes leads to different chemical and physical properties, which has been known from the 30s of the last century.[1, 2, 3] The biological significance of the natural abundance of D in living organisms and particularly in cell cycle regulation was not studied for six decades. The first scientific paper investigating the impact of D on cell growth was published in 1993[4]; since then the determinative role of the withdrawal of D has been already established for numerous biological systems, such as tissue culture of healthy and tumourous cell lines, animal studies, and human clinical applications.

The most striking discovery was that tumour cells proved to be extremely sensitive to D-depletion, resulting in tumour regression and may even cause the necrosis of the tumour. On the other hand, healthy cells are able to adapt to the decreasing D-concentration. The growth rate of different tumourous cell lines in tissue culture (PC-3 human prostate-, MCF-7 and MDA human breast adenocarcinoma-, HT-29 human colon carcinoma-, A4 human leukaemia, as well as M14 human melanoma cells) was significantly inhibited in culture media containing DDW.[4, 5, 6] The real time monitoring of human tumour cell lines cultured in D-depleted media showed, that low concentrations of D (25 to 135 ppm) results in a concentration-dependent inhibitory effect on cell growth rate in comparison to control cells cultured in media containing normal water (150 ppm D); the inhibitory effect was more pronounced when the D-concentration of the culture media was decreased in 3 to 5 steps.[7] The anticancer effect of D-depletion was also confirmed in animal models in vivo.[4, 6] Human breast carcinomas were xenotransplanted in laboratory mice, and the daily water intake of the animals was replaced with DDW instead of normal water in the treated groups. Eighty days long DDW treatment resulted in tumour regression in 70% of the transplanted laboratory animals and in some cases the tumour completely disappeared. D-depletion also inhibited the expression of certain genes (c-myc, H-ras, Bcl-2, K-ras, COX-2) having key roles in tumour development.[8] Expression of these genes was significantly lower after carcinogen exposure if laboratory animals were given DDW as drinking water compared to the control group not undergoing DDW treatment.

D-depletion is a new research area; growing evidence suggests that it may act as an effective tool both in the treatment and prevention of cancer in humans, too. The main principle of DDW administration is to replace the whole normal daily fluid intake with DDW resulting in decreased D- concentration in the body. Application of DDW starts in the majority of cases with 105 ppm D-content, which is then gradually decreased to 85-, 65-, and 45 ppm D in every 1 to 3 months.

In order to investigate whether DDW might exert an anticancer effect in humans, a phase 2 placebo controlled, double blind clinical trial was conducted with the enrolment of 44 prostate cancer patients.[9] The daily fluid intake was replaced with DDW (85 ppm D) for 4 months in the treated group (22 patients). All patients, both in the DDW-treated and in the placebo group (22 patients) underwent conventional oncological treatments. By the end of the four months long treatment, three times higher net decrease in cumulative prostate volume was found in patients taking DDW. Prostate specific antigen (PSA), which is elevated in the majority of prostate cancer cases, showed significantly higher decrease in the DDW treated group compared to the placebo group. Patients undergoing DDW treatment in addition to conventional therapies achieved longer survival, the signs and symptoms of prostate cancer diminished at a significantly higher rate and among other symptoms, urinary complaints ceased as a result of DDW treatment. In addition, the course of the disease was studied during the extended follow-up of prostate cancer patients, when patients (91 patients) underwent repeated 3-5 months long cures with DDW. The retrospective statistical evaluation showed that DDW cures prolonged the progression-free interval and a strong correlation was found between low PSA-values and DDW treatment periods. The method was effective also in those patients who have already had bone metastasis (32 patients) from prostate cancer at start of the first DDW treatment.

Breast cancer is a major health problem and is one of the most prevalent cancers in women. Early diagnosis, population-based screening with mammography and intensely developing therapeutic options provide the possibility for early multidisciplinary treatment, but still high morbidity and recurrence rates are characteristics for the disease. The data base of 232 DDW-treated breast cancer patients was retrospectively evaluated and median survival time was calculated in subgroups of patients.[10] DDW treatment supplemented and did not substitute conventional therapies. In comparison with published data on survival of breast cancer, DDW treatment in addition to conventional therapies noticeably prolonged survival both at primary and advanced stages of the disease. Moreover, repeated 4 to 5 months long cures resulted in outstanding survival. Those patients, who started the cure after successful conventional treatments at a tumour-free stage achieved extremely long progression-free interval. Data suggest that DDW treatment may contribute to the prevention of recurrences of the breast cancer.

Nowadays, the leading cause of cancer-related death is lung cancer; it is the most prevalent cancer both in men and women. Prognosis for lung cancer primarily depends on the histological subtype of the tumour, but staging, presence, localization, number of metastases and gender also affect survival. Supportive application of DDW was effective against non-small-cell lung cancer-, as well as small-cell lung cancer. Retrospective study of 129 lung cancer patients showed that D-depletion in addition to oncotherapies resulted in prolonged survival.[11] D-depletion was also applied successfully in advanced stages of lung cancer; it improved significantly the five-year survival rate even in metastatic small-cell lung cancer. Brain metastasis can develop rapidly from all histological types of lung cancer, and it might cause serious clinical complications resulting in poor prognosis. Patients with brain metastases from lung cancer achieved longer Median Survival Time (MST) when they received DDW treatment in addition to and then as an extension of conventional therapies.[12] The combined treatment resulted in regression of metastases and/or the primary lung tumour or halted the continuous progression that was irresistibly invasive prior to the use of DDW.

The best protocol for DDW treatment depends on the primary tumour, its histological type, and the staging of the disease. Patients may start the first DDW cure at diagnosis of neoplastic disease in addition to conventional therapies (surgery and/or chemotherapy, radiotherapy, biological treatments). After completion of the standard treatment regimens, it is advised to take DDW continuously, even if the patient is already in remission. On average, the first cure lasts for 6 to10 months, then it can be interrupted for 1 to 2 months. Although single DDW treatment can be effective, those patients, who subsequently repeat at least 3 months long cures, achieve significantly longer symptom-free period, and D-depletion was able to delay or halt relapses in different tumours. In order to get more insight in the application of DDW, two case histories are presented in the following sections.

Patient 1

A 53 years old man showed an elevated PSA of 11.9 ng/mL in June 2004; the subsequent biopsy detected adenocarcinoma cells in the prostate gland. No metastases were present at time of diagnosis. The patient’s prostate gland was surgically removed, the operation was followed by hormone therapy. At that time, significantly lower, but still elevated PSA level (6 ng/mL) was measured. At that time point the patient started to take DDW resulting in further decrease in the PSA-level. During the succeeding years, 12-16 weeks long DDW cures were repeated with 8 weeks long interruptions. DDW dose was increased in each cure; it was started with DDW containing D at a concentration of 105 ppm which was then changed for DDW of 85 ppm D after 8 weeks. The repeated cures with DDW were sufficient to maintain a PSA-level close to 0.0 ng/mL. Four years later progression was detected, therefore DDW dose was increased in the next cure that ensured further reduction of PSA again. Five years after the initial diagnosis, PSA-level was still steady and it was below 1.0 ng/mL.[9]

Patient 2

A 54-year-old female patient complained of vision problems; symptoms of brain compression were also detected in July 2001. The skull CT scan diagnosed a 20x30x40 mm tumour in the parieto-occipital lobe of the brain. Further examinations revealed that the patient suffered from a primary lung tumour in the 2nd and 3rd segments of the right lung, which gave rise to a single brain metastasis. The lung tumour reached 30x50x32 mm in size; histologically it proved to be small cell lung cancer having poor prognosis. Combined treatment of radiotherapy both to the chest and the skull, 6 cycles of cisplatinum-etoposide chemotherapy and concurrently DDW treatment (105 ppm D) were initiated. After completion of radiotherapy (October 2001) and chemotherapy (May 2002) as an extension of these the patient took DDW for more than a year; and the D-content of DDW was decreased in several steps to 50 ppm. As a result of conventional therapies and of the extended DDW treatment, complete response was diagnosed at the primary and the metastatic sites in February 2003. The first sustained DDW cure ended in June 2003. DDW treatment alone was repeated several times, the final cure was completed in April 2005. In January 2012 the patient still leads an active life. She took DDW for a total duration of 3.65 years (43.6 months) and 7 years after the last cure the patient was tumour free, she had no complaints and symptoms.[12]

DDW treatment in combination with, or as an extension of conventional therapies noticeably prolonged MSTs in the study populations of cancer patients. The method proved to be safe, and D-depletion may act as a highly effective modality both in prevention and as a supportive remedy in primary or advanced stages of cancer. We conclude that D-depletion offers additional benefits to standard treatment regimens in cancer and can be integrated easily in standard procedures.

References

1.         Katz JJ, Crespi HL. Isotope Effects in Biological Systems. in Collins CJ and Bowman N eds. Isotope Effects in Chemical Reactions. Van Nostrand Reinhold. New York. pp286-363. 1971.

2.         Rundel PW, Ehleringer JR and Nagy KA. Stable Isotopes in Ecological Research. Springer. New York. 1988.

3.         Jancsó G. Isotope Effects. in Vértes A, Nagy S and Klencsár Z eds. Handbook of Nuclear Chemistry, Volume 2. Kluwer Academic Publishers. Dordrecht, Netherland. pp85-116. 2003.

4.         Somlyai G, Jancsó G, Jákli Gy et al. Naturally occurring deuterium is essential for the normal growth rate of cells. FEBS Lett 317: 1–4. 1993.

5.         Somlyai G et al. Naturally occurring deuterium may have a central role in cell signalling. in Heys JR and Melillo DG eds. Synthesis and Applications of Isotopically Labelled Compounds. John Wiley and Sons Ltd. New York. pp137-141. 1998.

6.         Somlyai G, Laskay G, Berkényi T, et al. The biological effects of deuterium-depleted water, a possible new tool in cancer therapy. Zeitschrift für Onkologie/Journal of Oncology 30: 91–94. 1998.

7.         Nagy LI, Fábián G and Puskás LG. Effects of deuterium depleted water alone and in combination of known chemotherapeutic agents on different tumour cells. Abstract in: 2nd international congress on deuterium depletion. European Chemical Bulletin 1(1-2): 43. 2012.

8.            Gyöngyi Z and Somlyai G. Deuterium depletion can decrease the expression of c-myc, Ha-ras and p53 gene in carcinogen-treated mice. In Vivo 14: 437–439. 2000.

9.         Kovács A, Guller I, Krempels K et al. Deuterium depletion may delay the progression of prostate cancer. J Cancer Ther 2: 548-556. 2011.

10.            Krempels K, Somlyai I, Balog K et al. A retrospective study of survival in breast cancer patients undergoing deuterium –depletion in addition to the conventional therapies. Abstract in: 2nd international congress on deuterium depletion. European Chemical Bulletin 1(1-2): 46-47. 2012.

11.            Gyöngyi Z, Budán F, Szabó I et al. Deuterium Depleted Water Effects on Survival of Lung Cancer Patients and Expression of Kras and Bcl2 Genes in Mouse Lung. Nutrition and Cancer: An International Journal 65(2) 2013. (accepted for publication)

12.            Krempels K, Somlyai I and Somlyai G. A retrospective evaluation of the effects of deuterium depleted water consumption on four patients with brain metastases from lung cancer. Integrative Cancer Therapies 7(3): 172-81. 2008.

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