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 proto-oncogenes, we have conducted a clinical study in 129 patients with small cell and nonsmall 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 survival of lung cancer patients as a nontoxic anticancer dietary supplement, especially for women with tumors overexpressing cancer-related genes, because MST of DDW-consuming group was 2-4 times longer than it is generally observed in lung cancer patients.
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 patient survival with also 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 researches of anti-cancer effects and the underlying mechanisms of deuterium-depleted water.
To evaluate the inhibitory effect of deuterium-depleted water (DDW) on the proliferation of nasopharyngeal carcinoma (NPC) cells in vitro and explore the possible mechanism.
The growth inhibition of NPC cells and preosteoblast MC3T3-E1 cells following DDW treatment was measured by MTT assay and plate colony formation assay. The changes in migration and invasion of NPC cells were evaluated using Transwell and boyden chamber assays. The protein expression of proliferating cell nuclear antigen (PCNA) was determined using Western blotting. Flow cytometry was employed to evaluate the changes in cell cycle distribution after DDW treatment.
DDW with deuterium concentrations of 100, 75 and 50 ppm significantly suppressed the cell proliferation (P<0.05) and lowered colony formation capacity and invasiveness of the NPC cells (P<0.01). Western blotting demonstrated a down-regulated expression of PCNA in the cells by DDW. DDW also caused obvious cell cycle arrest in the NPC cells with reduced cells in S phase and significantly increased cells in G(1) phase (P<0.05). Rather than causing growth inhibition, DDW promoted the growth of normal control MC3T3-E1 cells.
DDW possesses selective biological effects to inhibit the proliferation of NPC cells in vitro, suggesting the potential of DDW as a novel nontoxic adjuvant therapeutic agent in antitumor therapy.
The concentration of deuterium is about 150 ppm (over 16 mmol/L) in surface water and more than 10 mmol/L in living organisms. Experiments with deuterium depleted water (30+/-5 ppm) revealed that due to D-depletion various tumorous cell lines (PC-3, human prostate, MDA, human breast, HT-29, human colon, M14, human melanoma) required longer time to multiply in vitro. DDW caused tumor regression in xenotransplanted mice (MDA and MCF-7, human breast, PC-3) and induced apoptosis in vitro and in vivo. Deuterium depleted water (25+/-5 ppm) induced complete or partial tumor regression in dogs and cats with spontaneous malignancies, it was registered as anticancer for veterinary use in 1999 (Vetera-DDW-25 A.U.V., 13/99 FVM). The hypodermic preparation of the registered veterinary drug was successfully tested in clinical investigations. Under the permission of the Hungarian Institute of Pharmacology (No. 5621/40/95) a randomized, double blind controlled, human Phase II clinical trial with prostate cancer was performed, in compliance with GCP principles, which exhibited a significant difference between the control and treated groups with respect to the examined parameters, median survival time and the extension of life-span. We suggest that cells are able to regulate the D/H ratio and the changes in the D/H ratio can trigger certain molecular mechanisms having a key role in cell cycle regulation. We suppose that not the shift in the intracellular pH, but the concomitant increase in the D/H ratio is the real trigger for the cells to enter into S phase. The decrease of D concentration can intervene in the signal transduction pathways thus leading to tumor regression. Deuterium depletion may open new perspectives in cancer treatment and prevention helping to increase the effectiveness of current oncotherapies.
Tissue depletion often occurs in patients with chronic obstructive pulmonary disease (COPD), even in those that are weight-stable. Limited data are available, however, about changes in body water compartments in chronic wasting diseases such as COPD. The purpose of this study was to measure body composition in severe COPD patients with special attention to fat-free mass (FFM) depletion and the distribution of body water compartments. Total body water (TBW) and extracellular water (ECW) were measured by deuterium and sodium bromide dilution techniques, respectively, in 38 COPD patients (age: 65 +/- 9 y, forced expiratory volume in 1 s: 38 +/- 14% of predicted) in a stable clinical condition. FFM was calculated by assuming a hydration coefficient of 73%. Underweight patients [body mass index (BMI; in kg/m2) < or = 21] were characterized by a significantly lower percentage fat mass than normal-weight patients, but no significant difference was found in the ratio of ECW to intracellular water (ICW)(BMI < or = 21: 0.72 +/- 0.12, BMI > 21: 0.71 +/- 0.16; NS). When the study population was divided into depleted patients (FFM/height2 < or = 15 kg/m2) and nondepleted patients (FFM/height2 > 15 kg/m2), there was no significant difference in the percentage fat mass, but the ECW-ICW ratio was significantly higher in the depleted patients (0.78 +/- 0.16) than in the nondepleted patients (0.66 +/- 0.12, P < 0.05); this was most pronounced in women. In conclusion, it was found that COPD patients with extreme FFM wasting are characterized by an increased ECW-ICW ratio despite a relatively spared fat mass.