THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE

Volume 10, Number 2, 2004, pp. 345348

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

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 CEGSs 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. 337344), 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 418
months (Okuda et al., 1987). Two of the four patients were
said to have taken 300600 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 Childrens
Hospital, Calgary, Alberta, Canada.
2 Parish Chemical Company, Vineyard, UT.

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discussion section of their paper, the authors raised the possibility of contamination, but attributed the nephrotoxicity
to CEGS rather than to the particular (and possibly contaminated) commercial preparations their patients consumed.

Corrections of the error

One (1) year later, additional cases of germanium-induced
nephropathy were published, along with renal biopsy data
of the four cases published the previous year by Okuda and
colleagues (Matsusaka et al., 1988). Although Okuda et al.
had reported that these two patients had consumed only
CEGS, the renal biopsy data published by Matsusaka et al.
demonstrated clearly that the supplement ingested had been
contaminated by germanium dioxide. The 1987 paper by
Okuda et al. is cited frequently in the subsequent scientific
literature, without the correction published by Matsusaka
and colleagues 1 year later.
Two (2) years later, 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., 1990). First, five cases were presented showing nephrotoxicity from high doses of germanium dioxide, with elevated blood urea nitrogen (BUN) and serum creatinine. Renal histology revealed vacuolar degeneration and, often,
interstitial edema. It should be mentioned that these patients
had all taken large doses, ranging from 27 g to 250 g (total) over 46 months (Sanai et al., 1990).
In the same paper and in one published the following year,
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., 1991). This study
was designed to assess the toxicity of consuming these two
compounds for 10 weeks. In the germanium-dioxidetreated
group, there was marked weight loss, anemia, and elevated
BUN levels, as well as evidence of elevated germanium concentrations in renal biposies. In contrast, neither toxic effects nor any renal lesions were found in the rats who were
given long-term high doses of CEGS.
One might think that these results, plus the 1988 correction, would have laid to rest any fears about the toxicity of
CEGS. However, it seems that once an error enters the scientific literature, it can take on a life of its own.

The perpetuation of one error

In the ensuing years, many papers have cited the erroneous 1987 paper by Okuda et al. as evidence of nephrotoxicity caused by germanium compounds (Krapf et al.,
1992; Schauss, 1991a, 1991b; Takeuchi et al., 1992; Tao
and Bolger, 1997). These authors apparently did not read
the correction by Matsusaka (1988) or Okudas own followup article in 1990 (Sanai et al., 1990). The two reports that
purported to be review papers represent particularly egregious errors, because they have been frequently cited in other
reviews (Schauss, 1991a; Tao and Bolger, 1997).

KAPLAN ET AL.

Careless reporting
There is also considerable confusion in the scientific literature about which germanium compounds patients have
taken and which compounds are organic. For instance, germanium citrate lactate* (sometimes abbreviated as ge-laccit) has sometimes been marketed as being an organic form
(see below) (Hess et al., 1993; Krapf et al., 1992), but it is
not an organogermanium compound. Luck and colleagues
(1999) reported a case of renal toxicity caused by germanium citrate lactate, taken at a high dose of 426 g over 6
months, which would be more than 2 g/d. The discussion
section of this paper begins with a statement that erroneously
categorizes germanium citrate lactate as an organic compound, along with CEGS and Spirogermanium. Shauss perpetuated the error in 1991 when he repeatedly referred to
germanium citrate lactate as an organogermanium (Schauss,
1991b). In reality, germanium citrate lactate has no stable
germaniumcarbon bond but only germaniumoxygen
bonds; hence germanium citrate lactate is merely a chelated
form of germanium dioxide.
The negative tone of the literature, although resting primarily on the 1987 error, seems to have affected other scientists interpretations of their own data. An example is the
study published by Anger et al. (1992), in which a large dose
of CEGS (1 g/kg day) resulted in no discernible toxic symptoms and no behavior problems. However, their summary
reported that they had found slight renal dysfunction, characterized by an increase in creatine [sic]. Perhaps this is
what they expected to find but, in reality, 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.f. Table 3 in the paper by Anger et al.).
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. 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. The authors
did not distinguish among different forms of germanium.
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. Again, there was no attempt to distinguish
among different forms of germanium in this title.
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,
germanium lactate-citrate, etc.

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GERMANIUM SESQUIOXIDE ERRORS

renal damage, three of which were apparently caused by

germanium, but the form ingested was not identified.
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). The woman died of lactic acidosis apparently
caused by acute liver and renal failure. Neither the title
nor the abstract of this paper specified the form of germanium ingested.
Takeuchi and colleagues (1992) reported on a single case
of fatal ingestion of an unspecified form of germanium in
a 55year-old woman. The authors stated: The compound
probably contained various germanium derivatives: in
fact, nuclear magnetic resonance revealed so many peaks
that it was difficult to determine specific details of the
compound (page 442). In other words, this patient definitely did not consume pure CEGS.
From the title of Okada et al.s paper, one would never
know that the researchers were reporting on chronic high
supplementation with inorganic germanium (Okada et al.,
1989). All three of their cases took the same preparation,
one that was said to be used commonly in Japan at that
time as an elixir. At 90 mg/d, all three suffered from kidney damage. 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; hence, the patients were
not taking an organic form of germanium, such as CEGS.
A study that provided valuable information about the
pharmacokinetics of germanium dioxide referred only to
germanium in the title, without specifying the form
(Shinogi et al., 1989).
As mentioned in a different context above, Luck et al. reported a case of renal failure that resulted from large (. 2
g/d) dose of germanium citrate lactate (Luck et al., 1999).
Like so many papers on this topic, the title uses the general word germanium without specifying the form and,
as mentioned earlier, this group of authors assumed
wrongly that germanium lactate citrate was an organic
form of the mineral.
Another study, published only in abstract form, reported
that germanium health supplements were nephrotoxic to
Wistar albino rats, when the supplements were administered in low doses (Taylor et al., 1991). In the text of their
paper the authors refered to the supplement as being CEGS
but, in reality, they purchased the supplement in a health
food store and did not analyze it (Taylor and Dobrota, personal communication, March 2002).

INFLUENTIAL DENUNCIATIONS
OF CEGS
Perhaps the most harmful error in the literature is the review article published by the U.S. Food and Drug Admin-

istration (Tao and Bolger, 1997), which evaluated much of

the research on germanium dioxide and CEGS. In the summary of results (Table 2, page 216), the two cases reported
in 1987 by Okuda et al. are listed as the only known cases
of toxic effects documented from CEGS. Oddly, 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,
1997): These two cases were reported by Okuda et al.
(1987) to have taken Ge-132 [CEGS], whereas Sanai et al.
(1990) reported that germanium dioxide was detected in the
Ge products (footnote in Table 2, p. 416). Unfortunately,
in the rest of this same paper, the authors continued to cite
the Okuda reference of 1987 as having demonstrated CEGS
toxicity.
The papers with warnings by Schauss have also been
influential, because they are often cited (Schauss, 1991a,
1991b). Schauss conducted no experimental or observational
work himself but only perpetuated the error from 1987. Also,
as mentioned above, he erroneously described germanium
citrate lactate as an organic compound.
One of the trade associations discouraging the use of
CEGS is the National Natural Foods Association. In their
backgrounder the Association states: The concern with the
use of Ge-132 is not primarily the organic compound itself,
but rather the potential contamination of a product with the
toxic inorganic forms of various germanium salts, such as
the highly toxic germanium dioxide. 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. People who buy CEGS, whether they are
manufacturers who encapsulate the product or consumers
who expect to benefit from it, should be furnished with a
product that has no harmful impurities. Adulteration of germanium products with toxic forms, such as germanium dioxide, has been at the root of much of the misinformation about
germaniums safety.

CONCLUSION
Ideally, errors in scientific citations would be rare and
would be corrected in succeeding years by subsequent publications. As described above, such is not always the case.
In a related investigation, Muir reported that two scientists
at the University of California, Los Angeles (M. Simkin and
V. Roychowdhury, Ph.D.) tracked a classic 1973 oft-cited
paper on the structure of crystals (Muir, 2002). Of 4300 citations, 196 had misprints, typically for volume, page, or
(Monthly newsletter to NNFA members) See article entitled
NNFAs stand on germanium, comfrey, and chaparral. in the
September 2002 issue of NNFA Today, (Volume 16, Number 8,
page 5). In this article, reference is made to the backgounder that
appears on the NNFA Web site at http://www.nnfa.org

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KAPLAN ET AL.

year. Computer modeling suggested that this number of miscitations would have occurred only if 78% of all citations were
cut and pasted from secondary sources. 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. It is likely that many authors did not examine the original research but read only secondary sources
that referred to the 1987 paper. The error was perpetuated particularly by review papers such as the one by the Food and
Drug Administrations Center for Food Safety and Applied
Nutrition (Tao and Bolger, 1997) in which the authors apparently relied on secondary sources.
The intention of these two companion papers is to set
the scientific record straight on CEGS, a compound with
promising clinical potential when not contaminated. We
have reviewed the compounds chemistry, its historical development in Russia, preclinical data showing anticancer
properties, as well as safety and absence of toxicity. In the
current manuscript we have shown how the record became
confused over the years, resulting in very influential but unsupportable censure. Throughout these papers, the underlying message has been that CEGS is safe, promising, and deserving of appropriate clinical investigation.

ACKNOWLEDGMENT
This research was supported in part by the Alberta Childrens Hospital Foundation.

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Address reprint requests to:

Bonnie J. Kaplan, Ph.D.
Alberta Childrens Hospital
1820 Richmond Road, SW
Calgary, Alberta T2T 5C7
Canada
E-mail: kaplan@ucalgary.ca

This article has been cited by:

1. Doo-Hyeon Lim, Ming-Hua Li, Eun-Hye Kim, Seung-Wook Ham. 2010. Synthesis of Novel
Organogermanium Derivative Conjugated with Vitamin C and Study of its Antioxidant Effects. Bulletin
of the Korean Chemical Society 31:7, 1839-1840. [CrossRef]
2. Erwin Rosenberg. 2009. Germanium: environmental occurrence, importance and speciation. Reviews
in Environmental Science and Bio/Technology 8:1, 29-57. [CrossRef]