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Germanium

The term “organic germanium” has become synonymous for Bis(2-carboxyethylgermanium) sesquioxide. While Bis(2-carboxyethylgermanium) sesquioxide can be accurately called “organic germanium”, this is somewhat akin to calling a Mercedes-Benz “an automobile”. A Mercedes Benz is indeed an automobile, but not all automobiles are a Mercedes-Benz. In like manner, not all organic germanium is Bis(2-carboxyethylgermanium) sesquioxide. Scientists report over 53 organic forms and upwards of 30 organic derivatives of germanium. This fact must be taken into consideration when researching the true physiological effects of Bis(2-carboxyethylgermanium) sesquioxide; which for purposes of convenience we will call germanium sesquioxide

Few nutritional products are so poorly understood and widely mistreated as germanium sesquioxide. Germanium sesquioxide is a safe and powerful ally to the body’s natural immune response and as such, offers numerous benefits. However, some proponents of germanium sesquioxide have adorned it with so many unsubstantiated claims that true benefits are occasionally obscured by “snake oil” myth and mysticism. On the other hand, some opponents consider germanium sesquioxide a highly dangerous substance and urge industries everywhere to voluntarily discontinue its promotion. Our goal is to provide accurate, easily understood information on this subject that also sheds light on the source of misunderstanding.


Background

Germanium is a trace element discovered in 1886 with characteristics similar to carbon, silicon and tin. Its properties make it useful in both health, and industrial applications. Germanium is ubiquitous in nature and our food supply but exists in relatively low amounts. Scientists estimate daily intake for most humans is between 0.1 and 4 mg.
Like many minerals, germanium exists in numerous forms. The form of a mineral greatly affects its biological activity and safety. Minerals like chromium, sodium, potassium, phosphorous and selenium are essential to health and wellness or even life itself. However, they also exist in forms that can be deadly. Fortunately, we generally know enough to avoid the deadly forms and benefit from proper levels of safe forms.
Germanium is one mineral for which considerable confusion still exists. The reckless acts of a few un-scrupled profiteers over a decade ago and the failure of scientists to correctly classify the different forms fostered over-generalized statements on the hazards of all germanium containing products. These elements, combined with an alarming departure by a few “scientists” from the true scientific method, set an ideal stage for misunderstanding.

Forms of Germanium

Understanding the difference between safe organic and dangerous inorganic forms of germanium is essential to fully appreciate the significant errors perpetuated in this area. These errors can be divided into four categories: failure to specify the form of germanium under investigation, failure to conduct studies with a pure form of material, failure to correctly classify the form being studied, and failure to comprehensively search published works.
Inorganic forms: Salts and oxides lacking germanium carbon bond are correctly categorized as inorganic forms. The most common inorganic form is Germanium dioxide (GeO2). Germanium lactate citrate (Ge-lac-cit) is a preparation of GeO2 in a buffered mixture of lactic and citric acid to make it more bioavailable. Inorganic forms of germanium can accumulate in the body and are associated with nephrotoxicity, acute renal failure, and death. The Ge-lac-cit preparation is especially bothersome as it is occasionally reported by scientist as an organic form 10, 11, 12, 13. Toxicity from inorganic forms is reported at dosages ranging from 13 to 426 grams over a period of months 12, 30. There is no doubt that elevated levels of inorganic germanium are harmful so we won’t spend a lot of time here. Our purpose is simply to provide the tools to readily identify and avoid them.

Organic forms: A distinguishing feature for all organic germanium compounds is the presence of a germanium carbon bond. As mentioned earlier, scientists report at least 53 organic forms 5 and upwards of 30 organic derivatives of germanium 6. This site, however, focuses only on germanium sesquioxide. We mention this merely to stress the fact that there is a lot of information available, and just because an article mentions “organic germanium” doesn’t necessarily mean that it involves germanium sesquioxide. On the other hand, some companies try to differentiate their germanium sesquioxide through name branding and occasionally attempt to conceal the fact that their product is actually germanium sesquioxide. These elements can make it somewhat difficult to sort through the available information and correctly determine which physiological effects can legitimately be attributed to germanium sesquioxide and which cannot. There are numerous alternate names for germanium sesquioide: Ge-132; SK 818; propagermanium; proxygermanium; repagermanium; to name a few. In an effort to eliminate potential confusion, we will generally use “germanium sesquioxide” to describe all of the alternate names.

Not all organic germanium compounds have physiological effects similar to germanium sesquioxide. Spirogermanium is just one example of this. Spirogermanium is a pharmaceutical attempt to make and patent a new organic germanium form for oncology studies 3, 58. Numerous clinical trials with marginal results for Spirogermanium are published. Spirogermanium, however, must not be confused with germanium sesquioxide. Nor should any benefits or adverse side-effects reported in Spirogermanium clinical trials be extrapolated to compounds beyond the scope of the studies 58-65.

History of Germanium Sesquioxide

Germanium sesquioxide was among the first reported organic germanium compounds. The belief that Dr. Kazuhiko Asai, a Japanese scientist, invented or discovered germanium sesquioxide is a common misconception perpetuated by an aggressive publicity machine. In truth, its discovery and the process for producing it, is justly ascribed to V.F. Mironov, a Russian chemist, who first submitted his work for publication in November of 1966. Mironov’s work apparently caught the attention of Dr. Kazuhiko Asai who capitalized on the biological activity of germanium sesquioxide and published his own work in respected Japanese literature seven years later. For this reason, Asai is generally credited with being the first to market a true organic germanium compound.

Import Restrictions

During the early to mid 1980’s, supplementation with germanium was quite popular especially in Japan 24. In some circles, dangerous inorganic forms of germanium imported from Asian countries were consumed in large quantities causing renal compromise and even some fatalities. This is partly on account of sloppy manufacturing controls, and partly because un-scrupled profiteers mixed organic germanium with cheaper inorganic forms to boost profits. Gross ignorance also played a significant role as most vendors and consumers did not discriminate between different forms of germanium. When efforts were made to distinguish between organic and inorganic forms, it is clear that even a few scientists got confused. For example, germanium lactate citrate was frequently reported and marketed as organic germanium when it is actually inorganic 10-12.

The sloppiness of foreign manufacturers, the dishonesty of a few profiteers, and the ignorance of the masses severely damaged the germanium industry. It wasn’t long before all germanium supplements were targeted by the FDA. An import alert issued on June 28, 1988 allows US Customs to seize all germanium products for supplemental use. This alert was revised in 1995 but remains in effect today More on this 67. In spite of the import restrictions, foreign material continues to slip through illegally. Businesses that rely on a foreign source run the risk of product seizure, penalties, and a damaged reputation. Fortunately, a substantial domestic source continues to supply a growing demand. With a perfect track record of safety since 1987, Designed Nutritional Products is a domestic source you can trust.

The Manufacturing Process Does Matter

Contamination of germanium sesquioxide with dangerous levels of inorganic salts occurs as a result of extreme carelessness or a wanton act. Meticulous process design and careful process controls virtually eliminate the likelihood of such contamination. However, germanium dioxide (GeO2) is not the only potential hazard associated with germanium sesquioxide.
Nitrogen content is indicative of an inferior manufacturing process, utilizing acrylonitrile. Acrylonitrile, also called vinyl cyanide, is a mutagenic carcinogen and any manufacturer utilizing this process is left with a serious dilemma. If excess acrylonitrile is not used, there is the risk of germanium dioxide (GeO2) contamination. When excess acrylonitrile is used, it invariably ends up in the final product for consumption. http://ptcl.chem.ox.ac.uk/MSDS/AC/acrylonitrile.html
The toxic effects of acrylonitrile are not the only concern. During the hydrolysis step of the manufacturing process, some of the excess acrylonitrile is converted to acrylamide. Acrylamide is a known toxin suspected of causing cancer, birth defects, heritable genetic mutations, neurological damage, and effects that can take years to become apparent. http://physchem.ox.ac.uk/MSDS/AC/acrylamide.html
Without testing, it is usually impossible to know what reagents were used in the manufacturing process for germanium sesquioxide. However, a simple google search can still be quite revealing. Designed Nutritional Products strongly recommends avoiding any source of germanium sesquioxide touting acrylonitrile as a reagent in its published manufacturing process. Designed Nutritional’s germanium sesquioxide is produced with our own process which completely avoids any nitrogen containing reagents that lead to undesirable contaminants.

Demonstrated Safety of Germanium Sesquioxide

The low toxicity of pure germanium sesquioxide is well supported by both animal and human studies. Scientific data demonstrates a margin of safety difficult to surpass with both acute and chronic exposure through various routes of administration.
A 1991 study conducted on Wistar rats demonstrated no toxic effects or renal histological abnormalities with 120 mg/kg/day of germanium sesquioxide over a 24 week period. Germanium sesquioxide did not concentrate selectively in any particular organ and was virtually all excreted unchanged via urine within 72 hours. In contrast, this same study showed that 75 mg/kg/day of GeO2 caused weight loss, elevated blood urea, renal compromise i.e. tubular atrophy and vacuolar degeneration. The conclusion of this study was that germanium sesquioxide exhibited extremely low toxicity.

Another rat study in 1992 reported no discernable toxic symptoms following a six month chronic dose of 1,000 mg/kg/day.
An animal study conducted in 1997 demonstrated that germanium sesquioxide is rapidly removed from plasma and does not accumulate in tissues.
Gerber GB, Leonard A. Mutagenicity, carcinogenicity and teratogenicity of germanium compounds. Mutation Research 1997;387(3):141-146.

Low toxicity for germanium sesquioxide exposure is further substantiated through human studies. Dosages of 25, 50, and 75 mg/kg were administered to 20 healthy volunteers. Routes of administration were varied as well as the duration of exposure. No unusual reactions, blood or urine values were observed. This study elevated gamma interferon production in a dose dependant fashion for 90% of test subjects. Rapid elimination from the body was also noted with 80% being excreted unchanged in the first 9 hours following administration7.

A critical observation in regards to the general toxicity of all substances was made by Paracelsus (1493-1541) over 500 years ago: "All substances are poisonous; there is none which is not a poison. The right dose differentiates a poison and a remedy." The wisdom of this statement is irrefutable when we consider that even pure water in sufficient quantity will kill. Once we accept this fact, it makes perfect sense to compare one substance to others thereby establishing a “relative” measurement of toxicity. This is precisely what led to the concept of LD50.

LD50 is the “Lethal Dose” of any given material required to kill 50% of a given population. LD50 data is typically stated in a dosage amount per every kg of body weight of a test subject. By this criterion, highly toxic materials always have a lower LD50 than less toxic materials. For obvious reasons, most LD50 data on any substance is collected from animal and not human testing. In spite of this, LD50 has proven quite reliable when extrapolating to human toxicity, and always provides a good point of reference. Published LD50 data for germanium sesquioxide is further evidence of its safety.

The reported LD50 for germanium sesquioxide is in excess of 6,300 mg/kg orally for mice, greater than 10,000 mg/kg orally for rats, and greater than 1,000 mg/kg intravenously for rats. Chronic exposure studies are equally impressive at 3,000 mg/kg orally for 6 months on rats with no toxicity, and 500 mg/kg intravenously for 6 months on dogs, also with no toxicity. Considering this data in its proper perspective, germanium sesquioxide is at least 1 (one) time safer than calcium carbonate 47, three (3) times safer than table salt 48, four (4) times safer than potassium chloride 48, and 23 times safer than chromium picolinate 49. "Safer Than Table Salt Article"

References

1. Massey P. Dietary supplements. Medical Clinics of North America 2002;86:127-147.
2. Maskarinec G, Murphy S, Shumay DM, Kakai H. Dietary changes among cancer survivors. Eur J Cancer Care 2001;10:12-20.
3. Gerber GB, Leonard A. Mutagenicity, carcinogenicity and teratogenicity of germanium compounds. Mutation Research 1997;387(3):141-146.
4. Jao S-W, Lee W, Ho Y-S. Effect of germanium on 1, 2-dimethylhydrazine-induced intestinal cancer in rats. Diseases of the Colon and Rectum 1990;33:99-104.
5. Sato I, Yuan BD, Nishimura T, Tanaka N. Inhibition of tumor growth and metastasis in association with modification of immune response by novel organic germanium compounds. Journal of Biological Response Modifiers 1985;4(2):159-168.
6. Komuro T, Kakimoto N, Katayama T, Hazato T. Inhibitory effects of Ge-132 (carboxyethyl germanium sesquioxide) derivatives on enkephalin-degrading enzymes. Biotechnology and Applied Biochemistry 1986;8(5):379-386.
7. Miyao K, Onishi T, Asai K, Tomizawa S, Suzuki F. Toxicology and Phase I studies on a novel organogermanium compound, Ge-132. In: Nelson JD, Grassi C, eds. Current Chemotherapy and Infectious Diseases. Washington, D.C.: American Society of Microbiology, 1980: 1527-1529.
8. Fujita H, Seto Y. Antiviral activity of 3-oxygermylpropionic acid polymer (SK-818). Pharmacometrics 1990;39(4):385-388.
9. Asano K, Yamano M, Haruyama K, et al. Influence of propagermanium (SK-818) on chemically induced renal lesions in rats. The Journal of Toxicological Sciences 1994;19:131-143.
10. Hess B, Raisin J, Zimmermann A, et al. Tubulointerstitial nephropathy persisting 20 months after discontinuation of chronic intake of germanium lactate citrate. American Journal of Kidney Diseases 1993;21:548-552.
11. Krapf R, Schaffner T, Iten PX. Abuse of germanium associated with fatal lactic acidosis. Nephron 1992;62:351-356.
12. Luck BE, Mann H, Melzer H, Dunemann L, Begerow J. Renal and other organ failure caused by germanium intoxication. Nephrology Dialysis Transplantation 1999(14):2464-2468.
13. Schauss AG. Nephrotoxicity in humans by the ultratrace element germanium. Renal Failure 1991;13(1):1-4.
14. Okuda S, Kiyama S, Oh Y, et al. Persistent renal dysfunction induced by chronic intake of germanium-containing compounds. Current Therapeutic Research 1987;41:265-275.
15. Matsusaka T, Fujii M, Nakano T, et al. Germanium-induced nephropathy: report of two cases and review of the literature. Clinical Nephrology 1988;30(6 - 1988):341-345.
16. Sanai T, Okuda S, Onoyama K, et al. Germanium dioxide-induced nephropathy: A new type of renal disease. Nephron 1990;54:53-60.
17. Tao SH, Bolger PM. Hazard assessment of germanium supplements. Regulatory Toxicology and Pharmacology 1997;25(3):211-219.
18. Takeuchi A, Yoshizawa N, Oshima S, et al. Nephrotoxicity of germanium compounds: Report of a case and review of the literature. Nephron 1992;60:436-442.
19. Schauss A, G. Nephrotoxicity and neurotoxicity in humans from organogermanium compounds and germanium dioxide. Biological Trace Element Research 1991;29(3):267-280.
20. Anger F, Anger JP, Guillou L, Papillon A. Subchronic oral toxicity (six months) of carboxyethylgermanium sesquioxide in rats. Applied Organometallic Chemistry 1992;6(3):267-272.
21. van der Spoel JI, Sticker BHC, Esseveld MR, Schipper MEI. Dangers of dietary germanium supplements. The Lancet 1990;336:117.
22. Raisin J, Hess B, M. B, et al. Toxicity of an organic germanium compound: deleterious consequences of a "natural remedy". Schweiz Med Wochenschr 1992;122(1-2):11-13.
23. Omata M, Kikuchi M, Higuchi C, et al. Durg-induced nephropathy: Our recent clinical experience. In: Tanabe T, Hook JB, Endow H, eds. Nephrotixicity of Antibiotics and Immunosuppressants. Amsterdam: Elsevier Science Publishers B.V., 1986: 15-20.
24. Okada K, Okagawa K, Kawakami K, et al. Renal failure caused by long-term use of a germanium preparation as an elixir. Clinical Nephrology 1989;31:219-224.
25. Taylor A, Dickson F, Dobrota M. Effects of germanium health supplements in the rat. Clinical Chemistry 1991;37(6):985.
26. Nagata N, Yoneyama T, Yanagida K. Accumulation of germanium in the tissues of a long-term user of germanium preparation dead of acute renal failure. J Toxicol Sci 1985;10:333-341.
27. Obara K, Saito T, Sato H, et al. Germanium poisoning: Clinical symptoms and renal damage caused by long-term intake of germanium. Japanese Journal of Medicine 1991;30:67-72.
28. Shinogi M, Masaki T, Mori I. Determination and biokinetics of germanium in mouse tissues by atomic absorption spectrometry with electrothermal atomization. J Trace Elem Electrolytes Health Dis 1989;3:25-28
29. Sanai T, Onoyama K, Osato S, et al. Dose dependency of germanium dioxide-induced nephrotoxicity in rats. Nephron 1991;57(3):349-354.
30. Sanai T, Okuda S, Onoyama K, et al. Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide. Kidney International 1991;40:882-890.
31. Masaki Y, Kumano K, Iwamura M, et al. Protective effect of an organic germanium compound on warm ischemia and prolonged kidney preservation. Transplanatation Proceedings 1989;21:1250-1251.
32. Wakabayashi Y. Effect of germanium-132 on low-density lipoprotein oxidation and atherosclerosis in Kurosawa and Kusanagi hypercholesterolemic rabbits. Biosci Biotechnol Biochem 2001;65(8):1893-1896.
33. Yang MK, Kim YG. Protective role of germanium-132 against paraquat-induced oxidative stress in the livers of senescence-accelerated mice. Journal of Toxicology and Environmental Health 1999;12(58):289-297.
34. Unakar NJ, Tsui J, Johnson M. Effect of pretreatment of germanium-132 on Na(+)-K(+)-ATPase and galactose cataracts. Current Eye Research 1997;16(8):832-837.
35. Fujii A, Kuboyama N, Yamane J, Nakao S, Furukawa Y. Effect of organic germanium compound (Ge-132) on experimental osteoporosis in rats. General Pharmacology 1993;24(6):1527-1532.
36. Fujita H, Kurono M, Toyoshima S. Effect of 3-oxygermylpropionic acid polymer (SK-818) on the incidence of spontaneous leukemia in AKR mice. Pharmacometrics 1990;39(4):389-395.
37. Aso H, Suzuki F, Ebina T, Ishida N. Antiviral activity of carboxyethylgermanium sesquioxide (Ge-132) in mice infected with influenza virus. Journal of Biological Response Modifiers 1989;8(2):180-189.
38. Aso H, Shibuya E, Suzuki F, et al. Antitumor effect in mice of an organic germanium compound (Ge-132) when different administration methods are used. Gan To Kagaku Ryoho 1985;12(12):2345-2351.
39. Kumano N, Ishikawa T, Koinumaru S, et al. Antitumor effect of the organogermanium compound Ge-132 on the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice. Tohoku Journal of Experimental Medicine 1985;146(1):97-104.
40. Kobayashi H, Komuro T, Furue H. 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.
41. Chen F, Zhang Q. Inhibitive effects of spirulina on aberrant crypts in colon induced by dimethylhydrazine. Zhonghua Yu Fang Yi Xue Za Zhi 1995;29(1):13-17.
42. Song WS. Experimental study on prevention of the colorectal cancer by China medical stone and the organogermanium compound. Zhonghua Yu Fang Yi Xue Za Zhi 1993;27(5):286-289.
43. Jang JJ, Cho KJ, Lee YS, Bae JH. Modifying responses of allyl sulfide, indole-3-carbinol and germanium in a rat multi-organ carcinogenesis model. Carcinogenesis 1991;4:691-695.
44. Ono M, Oka T, Yoshihara H, et al. Effect of NK-421 (bestatin) and Ge-132 on the cytotoxicity of spleen cells obtained from the tumor-bearing mice. Gan To Kangaku Ryoho 1982;9(10):1771-1777.
45. Aso H, Suzuki F, Yamaguchi T, Hayashi Y, Ebina T, Ishida N. Induction of interferon and activation of NK cells and macrophages in mice by oral administration of Ge-132, an organic germanium compound. Microbiology and Immunology 1985;29(1):65-74.
46. Nakada Y, Kosaka T, Kuwabara M, Tanaka S, Sato K, Koide F. Effects of 2-carboxyethylgermanium sesquioxide (Ge-132) as an immunological modifier of post-surgical immunosuppression in dogs. Journal of Veterinary Medical Science 1993;55(5):795-799.
47. Suzuki F, Brutkiewicz RR, Pollard RB. Ability of sera from mice treated with Ge-132, an organic germanium compound, to inhibit experimental murine ascites tumours. British Journal of Cancer 1985;52(5):757-763.
48. Suzuki F, Brutkiewicz RR, Pollard RB. Importance ot T-cells and macrophages in the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). Anticancer Research 1985;5(5):479-483.
49. Suzuki F, Pollard RB. Prevention of suppressed interferon gamma production in thermally injured mice by administration of a novel organogermanium compound, Ge-132. Journal of Interferon Research 1984;4(2):223-233.
50. Suzuki F. Suppression of tumor growth by peritoneal macrophages isolated from mice treated with carboxyethylgermanium sesquioxide (Ge-132). Gan To Kagaku Ryoho 1985;12(11):2122-2128.
51. Suzuki F, Brutkiewicz RR, Pollard RB. Cooperation of lymphokine(s) and macrophages in expression of antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). Anticancer Research 1986;6(2):177-182.
52. Suzuki F. Antitumor mechanisms of carboxyethyl-germanium sesquioxide (Ge-132) in mice bearing Ehrlich ascites tumors. Gan To Kagaku Ryoho 1987;14(1):127-134.
53. Ming X, Yin H, Zhu Z. Effect of dietary selenium and germanium on the precancerous lesion in rat glandular stomach induced by N-methyl-N'-nitro-N-nitrosoguanidine. Zhonghua Wai Ke Za Zhi 1996;34(4):221-223.
54. Ikemoto K, Kobayashi M, Fukimoto T, Morimatsu M, Pollard RB, Suzuki F. 2-carboxyethylgermanium sesquioxide, a synthetic organogermanium compound, as an inducer of contrasuppressor T cells. Experientia 1996;15(52):159-166.
55. Sato I, Nishimura T, Kakimoto N, Suzuki H, Tanaka N. Prevention of pulmonary metastasis of Lewis lung carcinoma and activation of murine macrophages by a novel organic germanium compound, PCAGeS. Biological Response Modifiers 1988;7(1):1-5.
56. Tanaka N, Ohida J, Ono M, et al. Augmentation of NK activity in peripheral blood lymphocytes of cancer patients by intermittent Ge-132 administration. Gan To Kagaku Ryoho 1984;11(6):1303-1306.
57. Mainwaring MG, Poor C, Zander DS, Harman E. Complete remission of pulmonary spindle cell carcinoma after treatment with oral germanium sesquioxide. Chest 2000;117:591-593.
58. Saiers JH, Slavik M, Stephens RL, Crawford ED. Therapy for advanced renal cell cancer with spirogermanium: A Southwest Oncology Group study. Cancer Treatment Reports 1987;71(2):207-208.
59. Falkson G, Falkson HC. Phase II trial of spirogermanium for treatment of advanced breast cancer. Cancer Treatment Reports 1983;67(2):189-190.
60. Eisenhauer E, Quirt I, Connors JM, Maroun J, Skillings J. A phase II study of spirogermanium as second line therapy in patients with poor prognosis lymphoma: An NCI Canada Clinical Trials Group study. Investigational New Drugs 1985;3(3):307-310.
61. Eisenhauer E, Kerr I, Bodurtha A, et al. A phase II study of spirogermanium in patients with metastatic malignant melanoma.: An NCI Canada Clinical Trials Group study. Investigational New Drugs 1985;3(3):303-305.
62. Goodwin JW, Crowley J, Tranum B, et al. Phase II trial of spirogermanium in central nervous system tumors: A Southwest Oncology Group study. Cancer Treatment Reports 1987;71(1):99 – 100.
63. Ettinger DS, Finkelstein DM, Donehower RC, et al. Phase II study of N-methylformamide, spirogermanium, and 4-demethoxydaunorubicin in the treatment of non-small cell lung cancer (EST 3583): An Eastern Cooperative Oncology Group study. Med Pediatr Oncol 1989;17(3):197-201.
64. Vogelzang NJ, Gesme DH, Kennedy BJ. A phase II study of spirogermanium in advanced human malignancy. American Journal of Clinical Oncology 1985;8(4):341-344
65. McMaster M, Greco F, Johnson D, Hainsworth J. An evaluation of combination 5-fluorouracil and spirogermanium in the treatment of advanced colorectal carcinoma. Investigational New Drugs 1990;8:87-92.
66. Mirabelli C, Badger A, Sung C, et al. Pharmacological activities of spirogermanium and other structurally related azaspiranes: Effects on tumor cell and macrophage functions. Anticancer Drug Design 1989;3:231-242.
67. Import Alert IA #54-07. Germanium Products Rev. September 13, 1995.

We truly live in an information age and I am a strong supporter of educating the public on the nutritional industry. However, more important than the dissemination of information is the dissemination of correct information. It's time to set the record straight. Few nutritional products are so poorly understood and widely mistreated as bis (2-carboxyethylgermanium) sesquioxide "germanium sesquioxide". Germanium sesquioxide shows considerable promise in immune support by boosting levels of gamma interferon in a dose dependant fashion 1-8. Studies indicate that Germanium sesquioxide may be effective in combating certain viral 9,10 and malignant conditions 11-18. Other studies suggest benefits toward free radical damage 19-21, cataracts 22, hypertension 23, and osteoporosis 24. So why does an influential organization within the nutritional industry consider germanium sesquioxide a highly dangerous substance unfit for commerce? 25

History:
Like many minerals, germanium exists in numerous forms. The form of a mineral greatly affects its biological activity and safety. Minerals like chromium, sodium, potassium, phosphorous and selenium are essential to health and wellness or even life itself. However, they also exist in forms that can be deadly. Understanding the difference between safe and dangerous forms, and the ability to positively discriminate between them is vital to the safe use of all germanium supplements.
Indistinguishable from germanium sesquioxide in appearance, germanium dioxide (GeO2) has tainted the reputation of the germanium supplement market 26-28. However, product contamination with dangerous levels of inorganic germanium occurs only as a result of extreme carelessness or a wanton act. Analytical testing is capable of detecting levels of contamination far below anything considered dangerous 29. Common sense dictates that careful processing and quality controls are necessary to insure the safety of germanium or any other supplement.
The image of germanium sesquioxide was tainted by the actions of a few reckless and un-scrupled profiteers over a decade ago. In the early to mid 1980’s when germanium supplementation was a burgeoning business, dangerous inorganic forms of germanium were sold as safe organic forms, causing numerous cases of renal compromise and some fatalities 30-33. This combined with the failure of "scientists" to correctly classify the different forms, generated considerable fear and confusion and fostered over-generalized statements on the dangers of germanium containing products. 26-28, 31, 34

A report issued in 1987 by Okuda et al. further compounded the misunderstanding. Two cases of renal toxicity were attributed to germanium sesquioxide 35. The discussion section of this publication suggested possible product contamination but still attributed the toxicity to germanium sesquioxide. However, the presence of GeO2 contamination in the Okuda et al. study was proven conclusively in a paper published the following year by Matsusaka. et al. 36. Two years later, Okuda himself revised his position on germanium sesquioxide by demonstrating the inherent safety of chronic high doses of germanium sesquioxide (240 mg/kg/day) and the toxic effects of GeO2 at 150 g/kg/day 37.
The original Okuda error of 1987 has been cited for fifteen years as evidence of germanium sesquioxide toxicity. This creates a false perception of a larger body of evidence against germanium sesquioxide. Subsequent authors of scientific publications 30, 32, 34, 38, 39 seem unaware that a correction was made in 1988 36 and that the subject of germanium sesquioxide toxicity was fully explored again in 1990 37.
The failure of published reviews to comprehensively consider published works is just a portion of the problem. Additional errors in scientific publications include the failure to distinguish the form of germanium under investigation, failure to conduct studies with a proven pure form of material, and failure to correctly classify a form as organic or inorganic.

Safety:
Overwhelming evidence supports the safety of pure germanium sesquioxide. Acute and chronic exposure to extremely high doses demonstrates a margin of safety difficult to surpass 38, 40-46. Relatively speaking, germanium sesquioxide is at least 1.5 times safer than calcium carbonate 47, 3 times safer than table salt 48, 4 times safer than potassium chloride 48, and 23 times safer than chromium picolinate 49.
An import alert issued on June 28, 1988 and revised in 1995 continues to prevent legal entry of any germanium supplements 50. Fortunately, a substantial domestic source continues to supply a growing demand. With a perfect track record of safety for fifteen years, Designed Nutritional Products is a source you can trust.
Considering the possible benefits of germanium sesquioxide, the extremely low toxicity, and the ability to detect harmful levels of contaminants, germanium sesquioxide is one product that demands a closer look.

References:
1. Aso H, et al. Microbiology and Immunology 1985;29(1):65-74.
2. Nakada Y, et al. Journal of Veterinary Medical Science 1993;55(5):795-799.
3. Suzuki F, et al. British Journal of Cancer 1985;52(5):757-763.
4. Suzuki F, et.al. Anticancer Research 1985;5(5):479-483.
5. Suzuki F. Journal of Interferon Research 1984;4(2):223-233.
6. Suzuki F. Gan To Kagaku Ryoho 1985;12(11):2122-2128.
7. Suzuki F, et.al. Anticancer Research 1986;6(2):177-182.
8. Suzuki F. Gan To Kagaku Ryoho 1987;14(1):127-134.
9. Fujita H, Seto Y. Pharmacometrics 1990;39(4):385-388.
10. Aso H, et al. Journal of Biological Response Modifiers 1989;8(2):180-189.
11. Fujita H, et al. Pharmacometrics 1990;39(4):389-395.
12. Kumano N, et al. Tohoku Journal of Experimental Medicine 1985;146(1):97-104.
13. Kobayashi H, et al. Gan To Kagaku Ryoho 1986;13(8):2588-2593.
14. Chen F, Zhang Q. Zhonghua Yu Fang Yi Xue Za Zhi 1995;29(1):13-17.
15. Song WS. Zhonghua Yu Fang Yi Xue Za Zhi 1993;27(5):286-289.
16. Ming X, et al. Zhonghua Wai Ke Za Zhi 1996;34(4):221-223.
17. Ikemoto K, et.al. Experientia 1996;15(52):159-166.
18. Mainwaring MG, et al. Chest 2000;117:591-593.
19. Masaki Y, et al. Transplanatation Proceedings 1989;21:1250-1251.
20. Wakabayashi Y. Biosci Biotechnol Biochem 2001;65(8):1893-1896.
21. Yang MK, Kim YG. Journal of Toxicology and Environmental Health 1999;12(58):289-297.
22. Unakar NJ, et al. Current Eye Research 1997;16(8):832-837.
23. C.C. Ho, et al. Pharmacology 1990;41:286-291
24. Fujii A, et al. General Pharmacology 1993;24(6):1527-1532.
25. NNFA Today, 16:1, 2002
26. van der Spoel JI, et al. The Lancet 1990;336:117.
27. Raisin J, et al. Schweiz Med Wochenschr 1992;122(1-2):11-13.
28. Omata M, et al. Amsterdam: Elsevier Science Publishers B.V., 1986: 15-20.
29. Designed Nutritional Products analytical method archives (available upon request).
30. Krapf R, et al. Nephron 1992;62:351-356.
31. Luck BE, et al. Nephrology Dialysis Transplantation 1999(14):2464-2468.
32. Takeuchi A, et al. Nephron 1992;60:436-442.
33. Okuda K, et al. Clinical Nephrology 1989;31:219-224.
34. Schauss AG. Renal Failure 1991;13(1):1-4.
35. Okuda S, et al. Current Therapeutic Research 1987;41:265-275.
36. Matsusaka T, et al. Clinical Nephrology 1988;30(6 - 1988):341-345.
37. Sanai T, Okuda S, Onoyama K, et al. Nephron 1990;54:53-60.
38. Tao SH, Bolger PM. Regulatory Toxicology and Pharmacology 1997;25(3):211-219.
39. Schauss A, G. Biological Trace Element Research 1991;29(3):267-280.
40. Sanai T, Okuda S, et al. Kidney International 1991;40:882-890.
41. Anger F, et al. Applied Organometallic Chemistry 1992;6(3):267-272.
42. Obara K, Saito T, Sato H, et al. Japanese Journal of Medicine 1991;30:67-72.
43. Miyao K, et al. Washington, D.C.: American Society of Microbiology, 1980: 1527-1529.
44. Gerber GB, Leonard A. Mutation Research 1997;387(3):141-146.
45. Ishida et al. United States Patent 1984; # 4473581.
46. Proc 11th Int. Cong., Chemother. 1980; 1527-1529.
47. Fisher Scientific North Carolina catalog; Calcium Carbonate MSDS.
48. Sigma Chemical MSDS database.
49. Expert Group on Vitamins and Minerals Secretariat Review of Chromium January 2000.
50. Import Alert IA #54-07 Germanium Products 1995 revision.


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