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Germanium-132

Germanium-132

Description

The trace element, germanium, is present in all plants and animals. Germanium-132 is the form of organic germanium which has been studied for its antiviral, immunostimulative and antioxidant action. Ge-132 also may function as a free-radical scavenger. The average daily dietary intake of germanium is approximately .5 to 3 mg/day.

One form of organic germanium-132, sold as a supplement by the name "Ge-132", was first synthesized in 1967 by Kazuhiko Asaia, a Japanese scientist. Other organic germanium supplements are also available. One of these germanium products include the compound called lactate-citrate-germanate (or germanium lactate citrate). Both products, Ge-132 and sanumgerman, contain elemental germanium bound organically.

Studies have shown germanium-132 protects cells against radiation damage in vitro. Since radiation damage is oxidative, this protection suggests germanium-132 has a highly antioxidative activity. In studies on experimental animals given the compound prior to exposure to high-level radiation, germanium-132 was found to have free radical scavenging activity.

Evidence from routine toxicity testing on experimental animals suggests germanium-132 stimulates the production of interferon and thus may have anticarcinogenic activity. Studies have been completed on the anti-cancer effects of germanium-132, both in experimental laboratory animals and hospitalized cancer patients and are in the process of being published.

Pure germanium is a good conductor. Since 1948, inorganic forms of industrial-grade germanium have been used commercially in the semi-conductor electronics industry. It is important to note industrial forms of inorganic germanium (i.e. elemental germanium, germanium oxide) are different from organic germanium-132. Industrial forms of germanium are potentially toxic and are not sold as nutritional supplements.



Method of Action

Goodman has speculated the molecular structure of organic germanium may be a factor in its therapeutic properties. Germanium has 32 electrons, 4 of which are in the outer shell. These 4 outer shell electrons are easily given up to other molecules in need of electrons, such as a singlet oxygen molecule or an oxidized protein.

This potential for giving up electrons is the likely explanation for the ability of germanium-132 to function as a free radical scavenger of toxic compounds.

Germanium-132 may be protective against such toxic heavy metals as mercury and cadmium, since it can bind and discharge hydrogen ions, thereby increasing the levels of oxygen. Germanium-132 raises the level of reduced glutathione, a free-radical scavenger, thereby affording protection against endogenously-produced free radicals.




Therapeutic Approaches

Therapeutic usage includes: AIDS, allergies, arthritis, candida, cholesterol, infections and pain syndromes, some of which are expanded upon in these selections.

Acquired Immunodeficiency Syndrome (AIDS)

Goodwin has theorized germanium-132 may be of benefit as an immunostimulant due the induction of interferon, activation of macrophages and T-suppressor cells, and augmentation of natural killer cell activity observed in vivo.


Cancer

Germanium-132 has been shown to have a significant effect on lung cancer during clinical trials. It was observed to cause tumor regression, improvement of immunological parameters and increased survival times. A double-blind placebo-controlled study of unresectable lung cancer patients treated with germanium-132 for 3 months showed similar results. Patients either received chemotherapy and a placebo, or chemotherapy with germanium-132. Patients were grouped according to the histology of their cancer, i.e., adenocarcinoma, squamous cell carcinoma and small or large cell carcinoma.

In experimental animal studies, germanium-132 has exhibited significant and reproducible antitumor activity against many types of cancers including: Ehrlich ascites, Walker adenocarcinoma 256, syngeneic bladder cancer BC47, Lewis lung 3LL, IMC carcinoma, ascites hepatomas AH66, ascites hepatomas AH 44, and hepatoma cell MH-134. Overall, survival rates were lengthened in experimental animals given germanium-132 in studies of the following cancers: lymphoma(L5178Y); Sarcoma S-18; leukemia cells L1210; 3 methylcholanthrene (MCA)-induced fibrosarcoma; and spontaneous breast tumors (in SHN mice).

Senile osteoporosis

Early evidence suggests germanium-132 may be beneficial in senile osteoporosis. A twelve month study of patients with senile osteoporosis showed that bone mass continued to decrease in controls, while patients receiving Ge-132 showed increasing levels. The germanium-132 patients had significantly decreased parathyroid hormone levels at the end of 12 months.




Toxicity Factors

Both germanium sesquioxide (Ge-132) and germanium lactate citrate will be reviewed. The use of other forms of germanium, such as germanium oxide, has produced neurotoxicity and liver damage, and is not recommended at this time.

No LD-50 has been detected for germanium-132. No animal died during acute toxicity studies, even when 40 ml/kg of liquid germanium-132 was administered orally, subcutaneously or intraperitoneally. In an acute toxicity study of orally administered germanium-132 on mice and rats, dosages of 5 to 10 gram/kg failed to produce any acceleration or depression of voluntary movements, lowering of reactions to stimulus or any other external symptoms. After 7 days of administration, postmortem examination of mice and rats showed no gross anatomical changes in the liver, kidneys, spleen or other organs.

The acute toxicity tests on animals for germanium lactate citrate have shown an oral dose LD-50 of 3,400 mg/kg body weight. This is interpreted to mean a 147 pound male would have to consume more than 231 grams (or slightly over 1/2 pound) of germanium lactate citrate to reach such toxic levels. Chronic toxicity studies of germanium lactate citrate show no adverse biochemical, hematological or morphological effects at an oral dose of 50 mg/kg per day after 24 weeks of such administration. For a 147 pound male, this would be equivalent to a daily dose of 3.4 grams for a similar period.

Germanium-132 is not totally free of side effects in humans, although no life-threatening side effects have been reported to date. In a 1976 study, thirty patients were given 2.1 grams of germanium-132 daily for up to 8 weeks after surgery. One minor complaint reported by some patients was softening of the stool, which reversed within 3 weeks of discontinuation. Some anecdotal reports from Canada and New Zealand have suggested prolonged use in some patients may result in sleep disturbance and/or changes in mental function. However, when germanium-132 was discontinued, these complaints diminished. The validity of these reports has not been assessed in any long-term studies of healthy subjects.

Pharmacological effects of germanium-132 have been extensively studied in rabbits, rats and mice. No abnormalities were observed in animals given either 1 gm/kg or 4 gm/kg of germanium intraperitoneally.

There are no reports of germanium-132 being carcinogenic. Evidence to date suggests when given to animals with various cancers, germanium-132 enhances survival time, slows down tumor growth or retards the spread of metastases.

Besides its rapid disappearance in both blood, tissues, and organs, after oral administration, almost 90% of C-14 labeled germanium-132 is eliminated from the body within 30 minutes after intravenous injection. Thereafter, radioactivity decreases slowly, in a biphasic fashion. Urinary excretion of i.v. administered germanium-132 amounts to about 68% in 1 hour and about 90% in 3 hours. Within 48 hours, excretion is about 95% complete. Total bile excretion of germanium-132 in 48 hours is only about 1%. Thus i.v. germanium-132 seems to be excreted very rapidly from the rat and does not accumulate in the body in appreciable amounts. Further confirmation of this has been provided by studies in which mice were injected intraperitoneally with C-14 labeled germanium-132 for 30 days, to prepare them for examination of possible accumulation in different body sites.

At one hour after the last injection, the autoradiogram showed high radioactivity in the urinary bladder and slight activity in the digestive organs, gastrointestinal contents and kidneys, the normal excretion routes of germanium-132.

Reproductive toxicity studies of Wistar rats and rabbits have been conducted. Only when oral doses reached 4 grams/kg did a significantly higher rate of absorbed fetuses and a slight retardation of body weight occur. However, no lasting significant effects were reported at lower concentrations of germanium-132. Teratogenicity studies performed at the Japan Experimental Medical Research Institute showed no abnormalities in morphology or sex ratio, except, again, at 4 gram/kg or more. No evidence of teratogenicity was found in a second trial on rats or rabbits, even when administered at a daily dosage 500 mg/kg intravenuously or up to 4 gram/kg orally.

Recommended dosages are usually within the range of: 100 - 300 mg per day.

References

Asai, K. Organic Germanium. Japan Publications: Tokyo, 1980.

Aso, H., Y. Hayashi, F. Suzuki & N. Ishida. Antitumor effect of organogermanium compound (Ge0132) in mouse tumors. Proc Jap Cancer Assoc., 1979: 38; 112-115, and pp 193-197.

Goodman, S. Therapeutic effects of organic germanium. Med Hypothesis, 1988: 26; 207-215.

Harisch, G. Glutathione and glutathione-dependent enzymes of the rat liver after different doses of Sanumgerman. 1st International Conference on Germanium. Lekim & Samochowiec (eds.) Semmelweis-Verlag, 1985.

Ishida, N., F. Suzuki, H. Asho & Y. Hayashi. (Japanese) Proc. Jap. Cancer Assoc., 1979: 193-198.

Kidd, P.M. Homeostatic normalizer and immunostimulant: a review of its preventive and therapeutic efficacy. Int Clin Nutr Rev., 1987: 7(1); 11-20.

Kobayashi, H., T. Komuro & Furue. Effect of combination immunochemotherapy with an organogermanium compound, Ge-132, and antitumor agents on C57BL/6 mice bearing Lewis lung carcinoma (3LL). Gan To Kagaku Ryoho, 1986: 13(8); 2588-2593.

Kuga, N., S. Oboshi, H. Sato & R. Sato. Inhibition of senile amyloidosis of mice by bis-carboxyethyl germanium sesquioxide. Acta Path Jap., 1976: 26(1); 63-71.

Kumano, N., K. Konno, et.al. Effect of carboxyethylgermanium sesquioxide on the methylcholanthrene induced tumorigenesis in mice. Report Res Inst Tuberculosis, Leprosy (Cancer, 1978: 25(3-4); 89-95.

Kumano, N. et.al. Antitumor effects of organogermanium compound (Ge-132) in mouse tumors. (Current Chemotherapy Infectious Disease Proceedings, 11th International Congress of Chemotherapy & 19th ICAAC). Am Soc Microbiology, 1980: 2; 1525-1527.

Kumano, N., T. Ishikawa, S. Koinumar, T. Kikumoto, S. Suzuki, Y. Nakai, & K. Konno. Antitumor effects of the organogermanium compound Ge-132 on the Lewis lung carcinoma (3LL) in C57BL6 (B6) mice. Tohoku J Exp Med., 1985: 146; 97-104.

Lekim, D. The biological activity of germanium. Presented at International Conference on organic germanium, Hanover, West Germany, October 1984.

Miyao, K., T. Onishi, K. Asai, S. Tomizawa & F. Suzuki. Toxicology and phase I studies on a novel organogermanium compound, Ge-132. Current Chemotherapy and Infectious Disease. J.D. Nelson & C. Grassi, eds. Am Soc for Microbiology: Washington, DC. 1979: pp. 1527-1529.

Mizushima, M., H. Satoh & K. Miyao. Some pharmacological and clinical aspects of a novel organic germanium compound Ge-132. 1st International Conference on Germanium. Lekim & Samochowiech, eds. Semmelweis-Verlag, 1985.

Nagai, H., Hasegawa & Shimpo. Reproductive study of rats intraperitoneally treated with carboxyethylgermanium sesquioxide (Ge-132). Pharmacometrics (Jap)., 1980: 20(2); 271-280.

Pharmacometrics (Jap), 1980: 20(4); 675-679.

Sato, I., B.D. Yuan, T. Nishimura & N. Tanaka. Inhibition of tumor growth and metastatic in association with modification of immune response by novel organic germanium compounds. J Biol Respns Mod., 1985: 4; 159-168.

Sato, I., T. Nishimura, N. Kakimoto, H. Suzuki & N. Tanaka. Presentation of pulmonary metastasis of Lewis lung carcinoma and activation of murine macrophages by a novel organic germanium compound, PCAGeS. J Biol Response Mod., 1988: 7(1); 1-5.

Schroeder, H.A. & J.J. Balassa. Abnormal trace metals in Man: germanium. J Chron Dis, 1967: 20; 211-224.

Shimp, K. & N. Mori. Teratogenicity tests of carboxyethylgermanium sesquioxide (Ge-132) given during the period of organogenesis, in rabbit.

Suzuki, F. et.al. Suppression and acceleration of experimental amyloidosis in mouse model. Acta Pathol Jap., 1980: 30(4); 557-564.

Suzuki, F. Antitumor mechanisms of carboxyethyl-germanium sesquioxide (Ge-132) in mice bearing Ehrlich ascites tumors. (Japanes) Gan To Kagaku Ryoho (Japan J Cancer Chemotherapy), 1987: 14(1); 127-134.

Suzuki, F. Ability of sera from mice treated with Ge-132, an organo-germanium compound, to inhibit experimental murine ascites tumors. Gan To Kagaku Ryoho, 1985: 12; 2314-2321.

Suzuki. Antitumor activity of Ge-132, a new organo germanium compound in mice is expressed through the functions of macrophages and T lymphocytes. Gan To Kagaku Ryoho, 1985: 12; 1445-1452.

Suzuki, F. Suppression of tumor growth by peritoneal macrophages isolated from mice treated with carboxy-ethylgermanium sesquioxide. Gan To Kagaku Ryoho, 1985: 12; 2122-2128.

Suzuki, G. & R.B. Pollard. Prevention of suppressed interferon gamma production in thermally injured mice by administration of a novel organogermanium compound, Ge-132. J Interferon Res., 1984: 4; 223-233.

Suzuki, F., R.R. Brutkiewicz & R.B. Pollard. Importance of T-cells and macrophages in the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). Anticancer Res., 1985: 5; 479-483.

Suzuki, F., R.R. Brutkiewicz & R.B. Pollar. Cooperation of lymphokine(s) and macrophages in expression of antitumor activity of carboxyethyl-germanium sesquioxide (Ge-132). Anticancer Res., 1985: 5; 479-483.