Written by Markus Horneber, Elke Wolf and the CAM-Cancer Consortium.
Updated February 28, 2017

Propagermanium

What is it ?

Names

International Union of Pure and Applied Chemistry (IUPAC): 3-[(2-Carboxyethyl-oxogermyl)oxy-oxogermyl]propanoic acid.
International Nonproprietary Name (INN): Propagermanium.
Other names/brand names: 2-carboxyethylgermasesquioxane, Ge-132, SK-818, Serocion, germanium sesquioxide, proxigermanium, repagermanium, organic germanium.

History / chemical structure / properties

The element germanium was discovered by the German chemist Clemens Winkler in 1886 1. It is located in the fourth main group of the periodic table of elements and detectable as a trace element in soil, seawater, plants, animals and carbon 2-5. Germanium is not considered an essential trace element as no vital biological functions and no syndromes of deficiency are known 6.

The Russian chemist V.F. Mironov first published the synthesis of an organic germanium compound in April 1967 7. This compound was a polymer of subunits with the formula [(GeCH2CH2COOH)2O3]n which today has the international non-proprietary name propagermanium.

Propagermanium has been produced and branded over the years with a confusing number of names by various manufacturers (see above). However Kaplan et al. refer in their review that all of these substance represent polymorphic forms of propagermanium, which are identical in aqueous solution 8.

Some other germanium compounds should not be confounded with propagermanium and are briefly addressed in the following.

Spirogermanium

In the late 70ies and 80ies, a completely different organic germanium compound was investigated for the use in cancer therapy: Spirogermanium (chemical name: 8,8-diethyl-N,N-dimethyl-3-aza-8-germaspiro[4,5]decane-2-propanamine). This substance was synthesized in 1974 and represents an azaspiran-germanium compound which was tested in various phase I/II trials to examine its antitumour effect.
Due to a markedly negative risk-benefit profile, in particular neurologic toxicity, spirogermanium was abandoned (reviewed by Kaplan et al. 8).

Inorganic germanium compounds

Two inorganic germanium compounds have been associated with renal damage: germanium dioxide (GeO2), which was contained in germanium supplements and elixirs sold over the counter as ingredient or contamination 9 and germanium lactate citrate, a chelated form of GeO2, sometimes erroneously referred to as organic germanium compound (reviewed by Kaplan et al. 8).

Claims of efficacy / mechanism of action / claimed indication

Germanium compounds have been popular as nutritional supplement since the 70ies 9-10. K. Asai, a Japanese scientist, first advertised beneficial effects on health in general and on the course of a multiplicity of illnesses, amongst others cancer 2.

Present-day providers and proponents of propagermanium mostly refer to the theoretical concept of K. Asai, who marketed propagermanium, which he claimed to have first synthesized and regarded as “the fountain of life, which animates the entire universe” under the name “Ge-132”. In his concept, Asai proclaimed a lack of oxygen due to stress and wrong nutrition as common causes of all diseases. He deduced from the chemical structure of “Ge-132” an ability to enrich the body with oxygen and to reduce hydrogen radicals, thus effectuating a detoxification and normalization of a disturbed electric potential in diseased organs 2.

These theories never have been proofed, however preclinical studies in animals and healthy humans suggested a dose-dependent induction of interferon γ and an activation of macrophages and NK cells 11-15.

Pharmacological aspects

An absorption rate of about 30% after oral administration of Ge-132 and rapid urinary excretion in a largely unmetabolized state was observed in a pharmacokinetic study on a small group of healthy adults 15.

Application

Propagermanium is usually sold as a powder or in capsules for oral administration. Dose recommendations vary highly among providers (100 to 6,000mg/day). In a case series doses of 30 mg/day 16, in one clinical trial 3,500 mg/day were applied 17.

Aspects of pharmaceutical drug and law regulations

In most countries propagermanium falls under the regulations of dietary supplements. An import alert on germanium products was imposed by the U.S. FDA in 1988, because of possible injury to health 18. In Germany governmental institutions warned consumers of possibly fatal kidney damage 19. In the UK supplements containing germanium were voluntarily withdrawn by the industry 6. In Japan propagermanium is approved for the treatment of HBe positive chronic hepatitis B 20.

Costs and expenditures

The monthly costs for a daily dose of 30 mg are 30 €, daily doses of 6,000 mg add up to about 1500 € per month.

Citation Markus Horneber, Elke Wolf, CAM-Cancer Consortium. Propagermanium [online document]. http://ws.cam-cancer.org/The-Summaries/Dietary-approaches/Propagermanium. February 28, 2017.

References

  1. A new Element: Germanium. Lancet 127, 562 (1886).
  2. Asai, K. Organisches Germanium - Eine Hoffnung für viele Kranke. Semmelweis-Verlag, 27316 Hoya (2001).
  3. Schroeder, H. A. & Balassa, J. J. Abnormal trace metals in man: germanium. J Chronic Dis 20, 211-224 (1967).
  4. Hara, S. et al. Determination of germanium in some plants and animals. Z Naturforsch [C] 45, 1250-1251 (1990).
  5. Lewis, B. L., Frolich, P. N. & Andreae, M. O. Methylgermanium in natural waters. Nature 313, 303-305 (1985).
  6. Expert group on vitamins and minerals. Risk assessment - Germanium. http://www.food.gov.uk/multimedia/pdfs/evm_germanium.pdf (last access: 02.06.2010). 2003.
  7. Mironov, V. F., Berliner, E. M. & Gar, T. K. Reactions of Trichlorogermane with Acrylic Acid and its Derivatives. Zhurnal Obshchei Khimil 37 Nr. 4, 962. 1967.
  8. Kaplan, B. J., Parish, W. W., Andrus, G. M., Simpson, J. S. & Field, C. J. Germane facts about germanium sesquioxide: I. Chemistry and anticancer properties. J Altern Complement Med 10, 337-344 (2004).
  9. Tao, S. H. & Bolger, P. M. Hazard assessment of germanium supplements. Regul Toxicol Pharmacol 25, 211-219 (1997).
  10. Kaplan, B. J., Andrus, G. M. & Parish, W. W. Germane facts about germanium sesquioxide: II. Scientific error and misrepresentation. J Altern Complement Med 10, 345-348 (2004).
  11. Suzuki, F., Brutkiewicz, R. R. & Pollard, R. B. Importance of T-cells and macrophages in the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). Anticancer Res 5, 479-483 (1985).
  12. Suzuki, F., Brutkiewicz, R. R. & Pollard, R. B. Ability of sera from mice treated with Ge-132, an organic germanium compound, to inhibit experimental murine ascites tumours. Br J Cancer 52, 757-763 (1985).
  13. Suzuki, F., Brutkiewicz, R. R. & Pollard, R. B. Cooperation of Lymphokine(s) and Macrophages in Expression of Antitumor Activity of Carboxyethylgermanium Sesquioxide (Ge-132). Anticancer Res 6, 177-182 (1986).
  14. Aso, H. et al. Induction of interferon and activation of NK cells and macrophages in mice by oral administration of Ge-132, an organic germanium compound. Microbiol Immunol 29, 65-74 (1985).
  15. Miyao, K., Onishi, T., Asai, K., Tomizawa, S. & Suzuki, F. Current Chemotherapy and Infectious diseases. Nelson, J. D. (ed.), pp. 1527-1529 (American society of Microbiology, Washington DC,1980).
  16. Tsutsumi, Y. et al. Effectiveness of propagermanium treatment in multiple myeloma patients. Eur J Haematol 73, 397-401 (2004).
  17. Mizushima, Y., Satoh, H. & Miyao, K. Germanium in biologischen Systemen. Lekim, D. & Samochowiec, L. (eds.), pp. 189-210 (Semmelweis-Verlag, 27316 Hoya,2007).
  18. FDA-import alert no.54-07. FDA-import alert no.54-07. 10-2-2009. Ref Type: Electronic Citation
  19. Bundesinstitut für gesundheitlichen Verbraucherschutz und Veterinärmedizin Warnung vor Germanium. Dtsch Ärztebl 97, 2418 (2000).
  20. Hirayama, C., Suzuki, H., Ito, M., Okumura, M. & Oda, T. Propagermanium: a nonspecific immune modulator for chronic hepatitis B. J Gastroenterol 38, 525-532 (2003).
  21. Brutkiewicz, R. R. & Suzuki, F. Biological activities and antitumor mechanism of an immunopotentiating organogermanium compound, Ge-132 (review). In Vivo 1, 189-203 (1987).
  22. Mainwaring, M. G., Poor, C., Zander, D. S. & Harman, E. Complete remission of pulmonary spindle cell carcinoma after treatment with oral germanium sesquioxide. Chest 117, 591-593 (2000).
  23. Hess, B. et al. Tubulointerstitial nephropathy persisting 20 months after discontinuation of chronic intake of germanium lactate citrate. Am J Kidney Dis 21, 548-552 (1993).
  24. Sanai, T. et al. Germanium dioxide-induced nephropathy: a new type of renal disease. Nephron 54, 53-60 (1990).
  25. Sanai, T. et al. Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide. Kidney Int 40, 882-890 (1991).
  26. Anger, F., Anger, J. P., Guillou, L., Sado, P. A. & Papillon, A. [Subacute and subchronic oral toxicity of beta-bis carboxyethyl sesquioxide of germanium in the rat]. J Toxicol Clin Exp 11, 421-436 (1991).