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THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE

Volume 10, Number 2, 2004, pp. 345–348
© Mary Ann Liebert, Inc.

Germane Facts About Germanium Sesquioxide:
II. Scientific Error and Misrepresentation
BONNIE J. KAPLAN, Ph.D.,1 G. MERRILL ANDRUS, Ph.D.,2 and W. WESLEY PARISH, Ph.D.2

ABSTRACT
The preceding paper reviewed the anticancer properties and safety of bis (2-carboxyethylgermanium)
sesquioxide (CEGS). An examination of those data leads one to question why this information has not stimulated clinical trials in patients with cancer. The answer is discussed in this paper, which traces the history to
an error published in the scientific literature in 1987. The reliance by subsequent authors on secondary sources,
citing only the error and not the correction published in 1988, constitutes part of the explanation of why CEGS
has been neglected. A second factor is also considered: careless reporting about any germanium-based compound as if the many thousands of germanium compounds were all the same. This combination of a publication error, careless writing, and the reliance on secondary sources appears to be responsible for the neglect of
the potential clinical use of this unique germanium compound.

INTRODUCTION

E

THE IMPACT OF SCIENTIFIC ERROR

rrors in the scientific literature are not unique to germanium. Particularly in the arena of natural health products, it is not unusual for scientific errors to lead to misdirected criticism and illogical policy decisions. A recent case
in point presented (Morley, 2001) and discussed in this journal (Jobst, 2001) involved the presentation and possible misrepresentation of data on the use of chiropractic. A similar
controversy exists in relationship to bis (2-carboxyethylgermanium) sesquioxide (CEGS). In this case, an error published in 1987 led to repeated neglect of the scientific literature that demonstrates CEGS’s anticancer potential in
animal models and, eventually, to denunciation of this trace
element in some very influential review papers. In this paper, we trace the history of the error, the subsequent corrections, the neglect of those corrections compounded by
careless reporting, and finally the censure by succeeding
publications.

The erroneous scientific report
In the 1970s and 1980s many people in Japan took
germanium-containing compounds as general health elixirs.
Some patients suffered renal problems: These patients were
generally found to have taken preparations containing inorganic germanium dioxide. As discussed in the companion
paper in this issue (pp. 337–344), the nephrotoxic effects of
germanium dioxide had been known since the early part of
the twentieth century and, unfortunately, this substance was
a frequent contaminant of the products that were consumed
by the public at that time.
In 1987, a group in Japan documented renal failure in
four people who consumed germanium compounds for 4–18
months (Okuda et al., 1987). Two of the four patients were
said to have taken 300–600 mg/d of CEGS, although the
supplements were not subjected to chemical analysis. In the

1 Departments of Paediatrics, and Community Health Sciences, Faculty of Medicine, University of Calgary, and Alberta Children’s
Hospital, Calgary, Alberta, Canada.
2 Parish Chemical Company, Vineyard, UT.

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. had reported that these two patients had consumed only CEGS. These authors apparently did not read the correction by Matsusaka (1988) or Okuda’s own followup article in 1990 (Sanai et al. The negative tone of the literature. 1997). is cited frequently in the subsequent scientific literature. 1988).. 1993. • Raisin and colleagues (1992) warned the German public about the safety of germanium citrate lactate because a woman with stage II human immunodeficiency virus (HIV) developed renal dysfunction after ingesting 47 g of this form. (1992). In the same paper and in one published the following year. 1991). which would be more than 2 g/d. the authors raised the possibility of contamination. there was no attempt to distinguish among different forms of germanium in this title. The authors did not distinguish among different forms of germanium. Again. Krapf et al. Okuda himself was a coauthor of a paper with both human and animal data demonstrating the lack of toxicity of high long-term doses of CEGS (Sanai et al. Although Okuda et al.” Perhaps this is what they expected to find but. • Omata and colleagues (1986) reported on eight cases of * Germanium citrate lactate is the correct nomenclature for a compound that is often referred to as germanium lactate citrate. and elevated BUN levels. KAPLAN ET AL. Sanai and colleagues (including Okuda) compared germanium dioxide at 150 mg/kg per day directly to CEGS at 240 mg/kg per day in Wistar rats (Sanai et al. .. The two reports that purported to be review papers represent particularly egregious errors.. For instance. 1992. Shauss perpetuated the error in 1991 when he repeatedly referred to germanium citrate lactate as an organogermanium (Schauss. along with CEGS and Spirogermanium. Table 3 in the paper by Anger et al. many papers have cited the erroneous 1987 paper by Okuda et al. the serum creatinine and urea remained within normal limits for rats and did not change at all after this unusually large dose of CEGS (c. Two (2) years later. as well as evidence of elevated germanium concentrations in renal biposies. First. An example is the study published by Anger et al. 1991b).. would have laid to rest any fears about the toxicity of CEGS. In contrast. with elevated blood urea nitrogen (BUN) and serum creatinine. because they have been frequently cited in other reviews (Schauss.. anemia.. Luck and colleagues (1999) reported a case of renal toxicity caused by germanium citrate lactate. there was marked weight loss. Takeuchi et al. 1997). However. In reality. Renal histology revealed vacuolar degeneration and. but it is not an organogermanium compound. ranging from 27 g to 250 g (total) over 4–6 months (Sanai et al. However. neither toxic effects nor any renal lesions were found in the rats who were given long-term high doses of CEGS. in which a large dose of CEGS (1 g/kg day) resulted in no discernible toxic symptoms and no behavior problems. One might think that these results. The 1987 paper by Okuda et al. The discussion section of this paper begins with a statement that erroneously categorizes germanium citrate lactate as an organic compound. taken at a high dose of 426 g over 6 months. seems to have affected other scientists’ interpretations of their own data. Schauss. the renal biopsy data published by Matsusaka et al. as evidence of nephrotoxicity caused by germanium compounds (Krapf et al. etc. without the correction published by Matsusaka and colleagues 1 year later. although resting primarily on the 1987 error. interstitial edema. Tao and Bolger. their summary reported that they had found “slight renal dysfunction. 1991a. Tao and Bolger. it seems that once an error enters the scientific literature. along with renal biopsy data of the four cases published the previous year by Okuda and colleagues (Matsusaka et al. hence germanium citrate lactate is merely a chelated form of germanium dioxide..346 discussion section of their paper. 1992. 1990). additional cases of germanium-induced nephropathy were published.. 1991a. plus the 1988 correction. The perpetuation of one error In the ensuing years. characterized by an increase in creatine [sic]. The following are some examples of these problems: • Van der Spoel and colleagues (1990) warned the public about the “Dangers of germanium supplements” in the title of a case report on a woman who developed nephrotoxicity after taking germanium citrate lactate. often.f. In the germanium-dioxide–treated group. but attributed the nephrotoxicity to CEGS rather than to the particular (and possibly contaminated) commercial preparations their patients consumed. in reality. it can take on a life of its own. 1992). germanium citrate lactate has no stable germanium–carbon bond but only germanium–oxygen bonds. This study was designed to assess the toxicity of consuming these two compounds for 10 weeks. Careless reporting There is also considerable confusion in the scientific literature about which germanium compounds patients have taken and which compounds are organic.). 1990). five cases were presented showing nephrotoxicity from high doses of germanium dioxide. It should be mentioned that these patients had all taken large doses. 1990). 1991b. germanium lactate-citrate. germanium citrate lactate* (sometimes abbreviated as ge-laccit) has sometimes been marketed as being an organic form (see below) (Hess et al. demonstrated clearly that the supplement ingested had been contaminated by germanium dioxide. Many researchers simply do not distinguish between safe and unsafe forms in papers and usually the titles of those papers are particularly misleading as they imply that the results are generalizable to any form of germanium. Corrections of the error One (1) year later.

org . p. Number 8.. has been at the root of much of the misinformation about germanium’s safety. Los Angeles (M. 1989). Tao and Bolger acknowledged in a footnote (footnote d) to that table the fact that subsequent reports demonstrated the presence of contaminating germanium dioxide (Tao and Bolger. in reality. but rather the potential contamination of a product with the toxic inorganic forms of various germanium salts. typically for volume. but the form ingested was not identified. page 5). At 90 mg/d. this group of authors assumed wrongly that germanium lactate citrate was an organic form of the mineral. As mentioned in a different context above. page 216).D. The authors stated: “The compound probably contained various germanium derivatives: in fact. Takeuchi and colleagues (1992) reported on a single case of fatal ingestion of an unspecified form of germanium in a 55–year-old woman. Adulteration of germanium products with toxic forms. All three of their cases took the same preparation. as mentioned earlier. It is only in the final paragraph of the Results section of this paper that the reader is informed that carbon 13-nuclear magnetic resonance (13C-NMR) spectroscopy revealed no carbon peak. People who buy CEGS. Like so many papers on this topic. 1999). (1987) to have taken Ge-132 [CEGS]. hence. nuclear magnetic resonance revealed so many peaks that it was difficult to determine specific details of the compound” (page 442). One of the trade associations discouraging the use of CEGS is the National Natural Foods Association. 1989). in the rest of this same paper. they purchased the supplement in a health food store and did not analyze it (Taylor and Dobrota.’s paper. From the title of Okada et al. one would never know that the researchers were reporting on chronic high supplementation with inorganic germanium (Okada et al.. Simkin and V.nnfa. reference is made to the backgounder that appears on the NNFA Web site at http://www. errors in scientific citations would be rare and would be corrected in succeeding years by subsequent publications. comfrey. In other words. 1991). Also. Luck et al. reported a case of renal failure that resulted from large (.) tracked a classic 1973 oft-cited paper on the structure of crystals (Muir. 1991b). such is not always the case. 2002). March 2002). when the supplements were administered in low doses (Taylor et al. such as germanium dioxide. CONCLUSION Ideally. In this article. published only in abstract form. three of which were apparently caused by germanium. The papers with warnings by Schauss have also been influential. Krapf and colleagues (1992) reported on a patient with breast cancer who died after ingesting large quantities of germanium citrate lactate (more than 2 g/d for over 2 months).347 GERMANIUM SESQUIOXIDE ERRORS • • • • • • renal damage. the patients were not taking an organic form of germanium. INFLUENTIAL DENUNCIATIONS OF CEGS Perhaps the most harmful error in the literature is the review article published by the U. which evaluated much of the research on germanium dioxide and CEGS. whether they are manufacturers who encapsulate the product or consumers who expect to benefit from it. without specifying the form (Shinogi et al. this patient definitely did not consume pure CEGS. reported that germanium health supplements were nephrotoxic to Wistar albino rats. Muir reported that two scientists at the University of California. A study that provided valuable information about the pharmacokinetics of germanium dioxide referred only to “germanium” in the title. and chaparral. The woman died of lactic acidosis apparently caused by acute liver and renal failure. Ph. In the text of their paper the authors refered to the supplement as being CEGS but. Food and Drug Admin- istration (Tao and Bolger. page. 2 g/d) dose of germanium citrate lactate (Luck et al. In their backgrounder† the Association states: “The concern with the use of Ge-132 is not primarily the organic compound itself. such as CEGS. all three suffered from kidney damage. In the summary of results (Table 2. (1990) reported that germanium dioxide was detected in the Ge products” (footnote in Table 2. or † (Monthly newsletter to NNFA members) See article entitled “NNFA’s stand on germanium. Roychowdhury. 1997): “These two cases were reported by Okuda et al. 416).. 196 had misprints.” It is evident that a CEGS product should be tested for the presence of germanium dioxide as well as for heavy metals and other dangerous impurities. 1991a. one that was said to be used commonly in Japan at that time as an elixir. such as the highly toxic germanium dioxide. because they are often cited (Schauss. In a related investigation. Another study. are listed as the only known cases of toxic effects documented from CEGS. the authors continued to cite the Okuda reference of 1987 as having demonstrated CEGS toxicity. personal communication. the two cases reported in 1987 by Okuda et al. Neither the title nor the abstract of this paper specified the form of germanium ingested. Oddly. should be furnished with a product that has no harmful impurities.” in the September 2002 issue of NNFA Today. Schauss conducted no experimental or observational work himself but only perpetuated the error from 1987. as mentioned above. As described above. 1997). (Volume 16. whereas Sanai et al.. he erroneously described germanium citrate lactate as an organic compound. Unfortunately.S. the title uses the general word “germanium” without specifying the form and. Of 4300 citations.

The misinformation in the scientific literature regarding CEGS seems to suggest a comparable pattern: Many papers cite the 1987 error and not the 1988 correction. Hazard assessment of germanium supplements. Hess B.‡ The intention of these two companion papers is to set the scientific record straight on CEGS. Fujimi S. Nanishi F. A case study of misrepresentation of the scientific literature: Recent reviews of chiropractic. Schauss AG. Matsusaka T. Renal failure caused by long-term use of a germanium preparation as an elixir. Shimamatsu K. Nephrol Dial Transplant 1999.13:1–4. Toxicity of an organic germanium compound: Deleterious consequences of a “natural remedy. Mann H. Imaizumi M. Biol Trace Elem Res 1991a.21:548–552. Shimomura S.7:1–3. Papillon A. Scientists exposed as sloppy reporters.30:341–345.122:11–13. Terai T. Guillou L. Clin Nephrol 1989. It is likely that many authors did not examine the original research but read only secondary sources that referred to the 1987 paper. Online document at: www.40:882–890. ‡ The authors would like readers to know that all English-language papers cited in these two papers were read in their entirety.41:265–275. 1986:15–20. Takaichi S. Bajo S. Address reprint requests to: Bonnie J. Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide. Taylor A.60:436–442. Kurata A. Redwood D. Tubulointerstitial nephropathy persisting 20 months after discontinuation of chronic intake of germanium lactate citrate. Mizuhira V. Kidney Int 1991. Dobrota M. Oda T. Oshikawa Y. Sticker BHC. Sanai T.7:65–78. Hess BMB. Sanai T. Rosner AL. the underlying message has been that CEGS is safe. resulting in very influential but unsupportable censure.31:219–224. Abuse of germanium associated with fatal lactic acidosis.newscientist. Persistent renal dysfunction induced by chronic intake of germanium-containing compounds.62:351–356. Effects of germanium health supplements in the rat.6:267–272. Imazeki N. Kawakami K. Horber F. Dangers of dietary germanium supplements. Jaeger P. Oochi N. Niwa H. Amsterdam: Elsevier Science Publishers B. Takeuchi A. Horber FF. Muir H.37:985. Takuma T. Fuse Y. Morizumi K. Bolger PM.. Ren Fail 1991b. Masaki T. Anger JP. a compound with promising clinical potential when not contaminated. Clin Nephrol 1988. eds. Sanaka S. Nephron 1992. Higuchi C. year. Kaplan. Kubota T.336: 117. Appl Organomet Chem 1992. J Trace Elem Electrolytes Health Dis 1989. Zimmermann A. Subchronic oral toxicity (six months) of carboxyethylgermanium sesquioxide in rats.jsp?id= ns99993168 Okada K. Kobayashi K. 1997) in which the authors apparently relied on secondary sources. Oochi N. The error was perpetuated particularly by review papers such as the one by the Food and Drug Administration’s Center for Food Safety and Applied Nutrition (Tao and Bolger. Oshima S. Oochi N. Nephron 1990. Fujishima M. 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29-57.This article has been cited by: 1. 2009. Synthesis of Novel Organogermanium Derivative Conjugated with Vitamin C and Study of its Antioxidant Effects. Seung-Wook Ham. Erwin Rosenberg. Bulletin of the Korean Chemical Society 31:7. 2010. importance and speciation. [CrossRef] . Ming-Hua Li. Doo-Hyeon Lim. Eun-Hye Kim. [CrossRef] 2. Germanium: environmental occurrence. Reviews in Environmental Science and Bio/Technology 8:1. 1839-1840.