 Organic Germanium 101 Demystifying the enigma of Germanium Sesquioxide Educational Seminar |
Germanium Sesquioxide, Organic Germanium, Bis (2-Carboxyethylgermaniumsesquioxide)
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Germanium Sesquioxide
Organic Germanium
Bis (2-Carboxyethylgermanium)sesquioxide
“We truly live in the information age where vast libraries are available at the touch of a button. Even in fairly narrow fields of study, so much information is readily available that sorting through it is a sizable task.
In our pursuit of truth we occasionally encounter contradicting information. However, if we look deep enough there is always a logical explanation. Truth is constant but what we perceive or accept as truth is always changing. This is merely because we are all subject to the frailties and limitations of being human.
At Designed Nutritional Products our goal is to weed out scientific errors that spread fear and confusion. Our websites and educational seminars are designed to provide tools of discernment in the face of apparent contradicting scientific evidence and enable people to make good decisions based on truth.”
David Parish / President
..........Organic Germanium:
- Introduction
- Background
- Forms of Germanium
- History of Germanium Sesquioxide
- Import Restrictions
- Analysis of an Import Alert
- The Value of Analytical Testing
- Analytical Testing for Germanium Sesquioxide
- The Manufacturing Process Does Matter
- Bad Science Dies Hard
- Demonstrated Safety of Germanium Sesquioxide
- References
FDA Actions Against Germanium Sesquioxide:
- FDA Confirms: Germanium Import Alert Still in Effect—May 9,2005
- Import Restrictions
- FDA Rejects Germanium NDI Submission
- FDA Cracks Down on Drug Claims and Misbranding
- FDA Cites Deaths Associated with Germanium Products
Importers Targeted by FDA:
- FDA Refuses Entry to a Shipment of Organic Germanium Destined for Vibrant Life
- Violation Code Against Vibrant Life
- FDA Refuses Entry of 20 Kilograms of Bulk Germanium Sesquioxide
Links of interest:
- Germanium Sesquioxide: "Safer than Table Salt"
- Value of a Domestic Source
- Made in USA Germanium Sesquioxide
- Certificate of U.S. Origin
- Import Alert is Not Cancelled
- Truth in Labeling for Retailers
- Germanium Sesquioxide Article Reprint "Peer Review"
- Why is There so Much Conflicting Information on Germanium Safety?
- Domestic Supply for Germanium Sesquioxide Exists
- Is Germanium Sesquioxide Legal?
- Price Disparity for Bulk Germanium Sesquioxide Source
Introduction
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.
Abstract 15165414 MEDLINE
Abstract 15165415 MEDLINE
Submitted for Publication 1966
Submitted for Publication 1967
For printed copies call us at 1.801.224.4518
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.
Analysis of an Import Alert
The following contains actual excerpts from an import alert issued by the FDA, against germanium products for human consumption. For convenience we have broken it down into the various sections of interest (and points of potential confusion) followed by an accurate analysis.
IA #54-07 - Revised 9/13/95, "GERMANIUM PRODUCTS"
****NOTE:...Import Alert #62-02, "Germanium Products" dated 06/28/88,
............is cancelled simultaneously with the issuance of this
............alert. The alert is revised to remove the food additive
............charge in accordance with the requirements of the Dietary
............Supplement, Health, and Education Act
............(DSHEA) of 1994.**** (source)
Analysis: At first glance one may assume that the import alert was cancelled in 1995 but nothing could be further from the truth. The import restriction against Germanium Sesquioxide has not been cancelled, but clearly states that an earlier alert issued in 1988 was cancelled, for the purpose of revising specific language, with the simultaneous issuance of another in 1995. The fact that this particular germanium import alert is still in effect was confirmed on May 9, 2005 by a compliance officer at the Dallas International activities Branch of the FDA. Anyone wishing to verify this can contact the FDA personally at: Food and Drug Administration
Dallas International Activities Branch. Compliance Officer: Catherine Vieweg
Ph: 1-800-991-4881 Email: cvieweg@ora.fda.gov
PROBLEM.......:...Poisonous and deleterious substance (PSNC) or
..................Unapproved new drug (DRND)
Analysis: These are the stated concerns of the FDA that led to the issuance of the import alert. The language “Poisonous and deleterious” was selected on account of contaminated material imported from Asian countries that caused nephrotoxicity (kidney damage) and even some fatalities between the mid to late 80’s. “Unapproved new drug” is used on account of the material being marketed to treat or mitigate disease related conditions. Both of these categories will be mentioned again later in the document
COUNTRY.......:...All
Analysis: This import alert against germanium products covers all countries of foreign origin.
MANUFACTURER
or SHIPPER....:...All
Analysis: This import alert against germanium products covers all manufacturers and shippers of imported germanium products.
CHARGES.......:..."The article is subject to refusal of admission
..................pursuant to Section 801(a)(3) in that it appears to
..................contain a poisonous and deleterious substance which
..................may render it injurious to health [Adulteration,
..................402(a)(1)]."
........................................ or
.................."The article is subject to refusal of admission
..................pursuant to Section 801(a)(3) in that it appears to
..................be a new drug within the meaning of Section 201(p)
..................without an approved new drug application [Unapproved
..................new drug, Section 505(a)]."
Analysis: Germanium products can be stopped at the U.S. border under either the poisonous and deleterious substance and/or the unapproved drug charge.
REASON FOR
ALERT.........:...Germanium is a nonessential trace element that has
..................caused nephrotoxicity (kidney injury) and death when
..................used chronically by humans, even at recommended
..................levels of use. Germanium containing products have
..................been labeled for drug use (e.g., with claims that
..................they are intended for use in the diagnosis, cure, ..................mitigation, treatment, or prevention of diseases such
..................as AIDS or cancer), although there are no approved
..................new drug applications (NDAs) or current
..................investigational new drug applications (INDs) on file.
..................Germanium containing products also have been offered
..................for entry as food products such as dietary
..................supplements.
Analysis: This portion clearly states the reasons the import alert against germanium was issued. Past incidences of injury and death gave reason for the FDA to conclude that germanium posed a significant health hazard. The fact that germanium products were being marketed for disease related conditions, and incidentally still are by many profiteers, justified the FDA in leveling a new unapproved drug charge. This is the first place that dietary supplements are specifically mentioned and targeted.
GUIDANCE.....:....Districts may detain all Germanium products offered
..................for entry, without physical examination, including
..................unlabeled bulk entries, except for semiconductor use
..................as discussed below. If the product claims to be
..................useful in the diagnosis, cure, mitigation, treatment,
..................or prevention of disease, use the drug charge;
..................otherwise use the "poisonous and deleterious" charge.
Analysis: Latitude is given to import / customs authorities to detain all germanium products without inspection. This covers bottled finished dosages in addition to bulk material. Specific instruction is given on what charges to use as justification for the action. The only germanium products exempt from this action are those intended for semiconductor use.
..................There are legitimate uses for germanium in the
..................semiconductor industry. If an importer shows that
..................the intended use of the product is other than for
..................human consumption, the entry should be released with
..................comment. If possible, appropriate follow up should
..................be made to assure the ultimate disposition is as
..................indicated by the importer.
Analysis: The FDA has determined that germanium can legitimately be imported for semiconductor use but not human consumption. Germanium for which the stated intended use is other than human consumption should be released and its ultimate disposition verified where possible.
..................Germanium may be offered for entry under a variety of
..................names including:
..................Germanium Sesquioxide
..................GE-132
..................GE-OXY-132
..................Vitamin "O"
..................Pro-Oxygen
..................Nutrigel 132
..................Immune Multiple
..................Germax
Analysis: This is a list of the popular names for germanium dietary supplements at the time the import alert was issued. These are the names of products that importers were offering for entry into the U.S. This does not instruct the FDA to allow these products in but simply flags the names they should be on the lookout for and detain.
One must not forget that sloppy process controls, greedy profiteers, rampant ignorance, and ineptitude led to this import alert being issued in the first place. Historically, reversing or canceling an import alert of this nature requires a far greater burden of proof than that which led to issuance of the alert. Designed Nutritional reaffirms its earlier position that any US importer of Germanium Sesquioxide is violating import restrictions that prevent the product from entering legally
The Value of Analytical Testing
Some published statements against germanium sesquioxide do not directly condemn it as a harmful substance. In fact, they correctly state “There are few adverse effects reported for germanium sesquioxide” However, they incorrectly imply that the potential for product contamination with toxic inorganic forms is high and difficult, if not impossible, to detect.
Proper analytical testing offers a high level protection and is capable of detecting levels of hazardous contaminants far below anything considered dangerous. Safe consumption of germanium sesquioxide is directly linked to the establishment of purity and positive identification of the source as a safe organic form. Comprehensive analytical testing is vital to correctly determining the identity and purity of germanium sesquioxide. For this reason, a few scientists have invested enormous amounts of time and capital in a wide spectrum of validated analytical methods.
Surprisingly, some germanium marketers are threatened by the mere suggestion of analytical testing; claiming that no adequate testing for germanium sesquioxide exists; claiming that a toxic combination of Vitamin C and germanium dioxide is indistinguishable from germanium sesquioxide by any analytical test. Misrepresentations of this magnitude are a serious concern. Similar ignorance and carelessness is what led to the negative perception of germanium today.
In truth, any source of germanium sesquioxide failing to conduct a full spectrum of analytical testing is simply unable to guarantee purity and quality beyond what is readily apparent from visual inspection. One of three logical conclusions can be drawn from any individual mounting an attack against scientifically validated analytical testing.
...1. This individual is technically inept and incapable of determining what he is actually selling.
...2. This individual is concerned that analytical results will be used as a measuring stick for determining true value at a reasonable price.
...3. This individual wants to avoid careful scrutiny of the product he sells. Why?
There is no “one” test for germanium sesquioxide that will tell you everything you should know about the product. However, the following is a list of analytical tests which, when properly combined and applied, will ensure the identity, purity, and safety of germanium sesquioxide.
Analytical Testing for Germanium Sesquioxide
..............Titration: An un-buffered saturated solution of Germanium Sesquioxide has a pH around 2.6. Based on the known structure, and the weight of the sample, the amount of NaOH needed to neutralize the product is a simple calculation. This test is conducted a minimum of three times. Dangerous levels of inorganic forms of Germanium will produce a low titration. Keep in mind that there are derivatives of germanium sesquioxide in the form of salts. These are not harmful but will also give a low titration.
..............Solubility: The solubility of a known amount of Germanium Sesquioxide is conducted in a known amount of boiling distilled water. GeO2 is not readily soluble in boiling water and is much more soluble in acid. Dangerous levels of GeO2 will produce a cloudy solution or insoluble material in the bottom of a flask.
..............Elemental Analysis: In its pure form, Germanium Sesquioxide contains 42.7% elemental Germanium. Dangerous levels of inorganic forms of Ge will register higher than 43.1% by atomic absorption. This will invariably be supported by a low titration and likely by a failed solubility.
..............X-ray Fluorescence: This sophisticated method for detecting germanium content is both easy and quantifiable. This method can be used to verify the results of elemental analysis.
..............X-ray Diffraction: This is a very sensitive method for detecting the presence of inorganic germanium contaminates. With the ability to detect less than 0.001%, this method is more than adequate for detecting harmful levels of inorganic germanium.
..............IR spectral analysis: While gross contamination with inorganic forms of Germanium will be evident with this method, IR analysis is generally used to quickly determine whether pure inorganic forms of Germanium are being mistaken for organic forms. Different polymorphs (crystal structures) of germanium sesquioxide will give slightly different IR spectra. This should be taken into consideration when being used to identify germanium sesquioxide.
..............13C-NMR: This method will reveal the presence of a germanium/carbon bond, an essential element in all organic forms of germanium. The presence of germanium and the lack of a germanium/carbon bond is a dead giveaway of a toxic inorganic form.
..............Kjedahl total nitrogen: Years ago, Designed Nutritional Products recommended this test as a screening method for certain manufacturing processes. This recommendation has now been picked up and echoed by numerous other individuals, though few could even tell you what a positive result indicates. Total nitrogen is a simple method to screen out germanium sesquioxide produced by an inferior manufacturing process utilizing acrylonitrile. More on this
..............HPLC: Properly designed HPLC analysis will positively determine the identity and purity of germanium sesquioxide. The identity of any trace impurities can be determined through additional testing.
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.
Bad Science Dies Hard
Good science is vital to progress and true learning. Contrastingly, sloppy science casts a shadow on even the most meticulous studies and leads to contradictions and confusion. Upon scrutiny, there is always a logical explanation for an apparent contradiction but once in the public domain it is nearly impossible to entirely remove the effects of bad science. The following are examples of sloppy science that have helped foster over-generalized concerns regarding the safety of all germanium containing compounds.
A report issued in 1987 by Okuda et al. damaged the reputation of germanium sesquioxide considerably. Two cases of renal compromise were attributed to germanium sesquioxide 14. The discussion section of this report suggested possible GeO2 contamination but still attributed the toxicity to germanium sesquioxide. The presence of GeO2 contamination in the Okuda et al. report was proven conclusively in a paper published the following year by Matsusaka. et al. 15. Two years later, Okuda revised his earlier position on germanium sesquioxide by demonstrating the safety of chronic high doses of germanium sesquioxide (240 mg/kg/day) and the toxic effects of GeO2 at 150 mg/kg/day 16.
Unfortunately, the damage had already been done. The original Okuda error of 1987 has been cited for nearly twenty years as the greatest evidence of germanium sesquioxide toxicity. In fact, it has been cited in so many articles that a false perception of a larger body of evidence against germanium sesquioxide resulted. Subsequent authors of scientific publications 30, 32, 34, 38, 39seem unaware that a correction was made in 1988 36 and that the subject of germanium sesquioxide toxicity was fully explored again in 1990 37. This was a simple mistake that the perpetrator attempted to correct. Imagine the impact of scientists who are unaware of or refuse to acknowledged their errors
1. Anger F, Anger JP, Guillou L, Papillon A. Subchronic oral toxicity (six months) of carboxyethylgermanium sesquioxide in rats. Applied Organometallic Chemistry 1992;6(3):267-72.
Analysis: This rat study was conducted with extremely high dosages of germanium sesquioxide (1,000 mg/kg/day) for six months produced no detectable toxic effects. The summary reports mild kidney dysfunction but this claim appears biased toward the negative perceptions of germanium sesquioxide. The data presented in table 3 of this paper, in fact, shows all kidney parameters to be normal and unchanged in spite of such a large dose.
2. Krapf R, Schaffner T, Iten PX. Abuse of germanium associated with fatal lactic acidosis. Nephron 1992;62:351-356.
Analysis:This paper reports a death associated with a high dosage of Ge-lac-cit (2g/day). Neither the title nor the abstract correctly distinguishes this as an inorganic form.
3. 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.
Analysis: Once again the culprit in this study is the inorganic form of Ge-lac-cit in excess of 2 g/day . This is the same group who has incorrectly classified this form as “organic” on previous occasions. The general mention of germanium in the title implies a hazard associated with all germanium compounds.
4. 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.
Analysis:This report fails to place adequate emphasis on the fact that all three cases of renal failure were caused by high doses of an inorganic germanium form. The fact that no organic forms were ingested was determined with 13C-NMR. This information, however, is only mentioned deep within the text.
5. Omata M, Kikuchi M, Higuchi C, et al. Drug-induced nephropathy: Our recent clinical experience. In: Tanabe T, Hook JB, Endow H, eds. Nephrotoxicity of Antibiotics and Immunosuppressants. Amsterdam: Elsevier Science Publishers B.V., 1986: 15-20.
Analysis: This study mentions three cases of renal damage attributed to germanium but no effort is made to determine the form of germanium ingested.
6. 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.
Analysis: This article incorrectly classifies Ge-lac-cit as an organic form thereby furthering the perception that organic forms are also hazardous.
7. 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.
Analysis: This review reports a single fatality attributed to germanium. The NMR data, however, suggests a mixture of several compounds. Admittedly the true composition was never determined
8. Taylor A, Dickson F, Dobrota M. Effects of germanium health supplements in the rat. Clinical Chemistry 1991;37(6):985.
Analysis: This study fails to establish whether the supplement ingested was in fact a pure form of germanium sesquioxide. The reported toxicity at low doses is more congruent with an inorganic form and it is clear from published literature that adulterated material has skewed test results in the past.
9. Van der Spoel JI, Sticker BHC, Esseveld MR, Schipper MEI. Dangers of dietary germanium supplements. The Lancet 1990;336:117.
Analysis:The very title of this letter strikes out at all germanium supplements. Nowhere is there a distinction between organic forms and the toxic inorganic form of Ge-lac-cit reported to cause the problem.
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"
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3. Gerber GB, Leonard A. Mutagenicity, carcinogenicity and teratogenicity of germanium compounds. Mutation Research 1997;387(3):141-146.
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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.
FDA Confirms Germanium Import Alert Still in Effect
May 10, 2005
The Import Alert against Germanium Sesquioxide is NOT cancelled, though some importers will say just about anything to convince you otherwise. This matter is quickly put to bed by simply asking the agency that issued it.
Designed Nutritional has long maintained that importation of Germanium products intended for human consumption is illegal under restrictions outlined in IA #54-07 - Revised 9/13/95, "GERMANIUM PRODUCTS". This Import Alert is readily available and easily understood. However, lest there be any question as to the legitimacy of this interpretation, Designed Nutritional recently contacted the FDA for comment.
According to Compliance Officer Catherine Vieweg, employed by the Dallas International Activities Branch of the FDA, Import alert #54-07 http://www.fda.gov/ola/2004/dietarysupplements0324.html
is still considered in effect as of May 9, 2005.
Email correspondance: FDA’s Current Stand on Germanium Importation
-----Original Message-----
From: Vieweg, Catherine [mailto:CVIEWEG@ORA.FDA.GOV]
Sent: Monday, May 09, 2005 12:34 PM
To: 'david@designednutritional.com'
Cc: Caterinevieweg@fda.org.hhs.gov
Subject: RE: Import Alert Clarification
The Import Alert currently posted is in effect. I suspect where the 1995 date comes from is that there was an adjustment to what charges would be used to detain such a product after the Dietary Supplement Health Education Act was passed. That didn't eliminate the Import Alert, just altered it a bit.
-----Original Message-----
From: David [mailto:XX@designednutritional.XXX]
Sent: Monday, May 09, 2005 1:25 PM
To: Vieweg, Catherine
Cc: Caterinevieweg@fda.org.hhs.gov
Subject: Import Alert Clarification
Dear Caterine,
There is some confusion as to whether the following import alert is still in effect. I believe it is, yet another individual importing this material from Japan or China, claims this import restriction was cancelled in 1995. Could you provide the FDA's official stand on this issue? The actual document is found at http://www.fda.gov/ora/fiars/ora_import_ia5407.html.
IA #54-07 - Revised 9/13/95, "GERMANIUM PRODUCTS"
****NOTE: Import Alert #62-02, "Germanium Products" dated 06/28/88, is
cancelled simultaneously with the issuance of this alert. The alert
is revised to remove the food additive charge in accordance with the
requirements of the Dietary Supplement, Health, and Education Act
(DSHEA) of 1994.****
Regards,
Dave Parish
Importers who continue to bring Germanium Products into the U.S., in spite of restrictions that prevent them from legally doing so, are in violation of Federal Import and U.S. Bioterrorism Laws. We encourage every importer of Germanium to personally verify this fact. Contact information is provided below
Food and Drug Administration
Dallas International Activities Branch.
Compliance Officer: Catherine Vieweg
Ph: 1 800 991 4881
cvieweg@ora.fda.gov
FDA Rejects Germanium NDI Submission
The following contains excerpts from a correspondence between Geranti Pharma, a Korean manufacturer of Germanium products, and the FDA. This occurred in November of 2002 following Geranti’s submission of a NDI for their germanium yeast product. Such correspondence clearly demonstrates the FDA’s continued resistance to letting germanium products for human consumption into the country. The complete document in PDF format can be examined at the link provided below.
Nov 13, 2002
Department of Health and Human Services
Food and Drug Administration
FDA has carefully considered the information in your submission, and the agency has significant concerns about the evidence on which you rely to support your conclusion that dietary supplements containing Geranti Bio-Ge, when used under the conditions recommended or suggested, will reasonably be expected to be safe. Specifically, FDA continues to have concerns about the use of germanium and germanium-containing compounds in dietary supplements and nothing in your submission provides a basis to conclude that germanium use is safe. Prolonged intake of products containing germanium has been reported to be associated with various adverse effects including renal dysfunction, anemia, myopathy, neurotoxicity, and nephrotoxicity in several human cases 1-4. The studies referenced in your notification are not sufficient to demonstrate that use of your Granti Bio-Ge would not cause the adverse effects noted in the literature to be associated with the intake of germanium.
For the reasons discussed above, the information in your submission does not provide an adequate basis to conclude that Geranti Bio-Ge, when used under the conditions recommended or suggested in the labeling of your product, will reasonably be expected to be safe. Therefore, your product may be adulterated under 21 U.S.C. 342(f)(1)(B) as a dietary supplement that contains a new dietary ingredient for which there is inadequate information to provide reasonable assurance that such ingredient does not present a significant or unreasonable risk of illness or injury. Introduction of such a product into interstate commerce is prohibited under 21 U.S.C. 331(a) and (v). See Source
FDA Refuses Entry of 20 Kilograms of Bulk Germanium Sesquioxide
Designed Nutritional Products has long maintained that the intent of the germanium import alert (revised in 1995) has always been to prevent importation of germanium products destined for human consumption. Our claim has been highly criticized by competitors who rely on a foreign source and some have gone to extreme measures to justify their actions. However, reality is a tough and relentless adversary. The following germanium sesquioxide entry refusal was reported by the Food and Drug Administration, the Department of Health and Human Services, and the Department for Homeland Security in October of 2003.
Germanium Sesquioxide
“In October 2003, FDA refused an entry of 20 kilograms of bulk germanium sesquioxide valued at $16,500, destined for use in human dietary supplements. Germanium has caused nephrotoxicity (kidney injury) and death when used chronically by humans, even at recommended levels of use.”
FDA:
http://www.fda.gov/ola/2004/dietarysupplements0324.html
Homeland Security and Governmental Affairs
http://hsgac.senate.gov/index.cfm?
Department of Health and Human Services
http://www.hhs.gov/asl/testify/t040608b.html
FDA Cracks Down on Drug Claims and Misbranding
As pointed out previously, it is quite common to hear unapproved drug claims from individuals selling germanium sesquioxide. This is unfortunate as it gives the FDA reason to seek more aggressive actions against germanium products. You’ll find that this is one of the charges leveled by the FDA against germanium in the import alert issued in 1988 and revised in 1995. Profiteers make such claims in order to boost sales, and count on a remote possibility of being caught. The following are excerpts from a warning letter sent to HBX, Inc. May 13, 2004 on account of misbranding and unapproved drug claims associated with their Ge-132 OXY Germanium
"The Food and Drug Administration (FDA) has reviewed your web site at the following address: http://www.germaniumus.com. This review shows serious violations of the Federal Food, Drug, and Cosmetic Act (the Act) in the labeling of your product GE-132 OXY Germanium. You can find the Act and implementing regulations through links on FDA’s Internet home page at www.fda.gov.
Under the Act, articles intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease in man are drugs [Section 201(g)(1)(B) of the Act]. Your web site claims that your product is useful in the prevention, treatment, or mitigation of diseases.
Your web site contains the following claims:
“Who should take germanium? Cancer patients, people recovering from cancer operations, and people undergoing chemotherapy. Also effective against diabetes, arthritis, paralysis and Alzheimer’s.”
“Those people who need germanium are as follows: Cancer patients during chemotherapy and radiation or after an operation- Aids, Alzheimer, Lyme disease, Parkinson disease and diabetes, . . . Hepatitis A, B, C, D, E-Heart Disease, High Blood Pressure, Rheumatoid Arthritis, . . . Asthma, . . . relief from Chronic Fatigue, . . . and other incurable diseases.”
“[G]ermanium has shown to be remarkably effective in treating lung cancer, cancer of the bladder, breast cancer, neurosis, asthma, diabetes, high blood pressure, heart failure, empyema, neuralgia, leukemia, encephalomalacia, uterine myoma, and cirrhosis of the liver.”
These claims cause your product to be a drug, as defined in section 201(g)(1)(B) of the Act. Because the product is not generally recognized as safe and effective when used as labeled, it is also a new drug as defined in section 201(p) of the Act. Under section 505 of the Act, a new drug may not be legally marketed in the United States without an approved New Drug Application (NDA).
Your web site (http://www.germaniumus.com) contains pictures of the seal of the FDA. The seal is displayed on your web site at numerous places, including the home, purchase, testimonial, and health tips pages. Your product is not approved by FDA, nor has FDA reviewed its formulation or the representations made for it. FDA believes that use of the FDA seal in the manner you have chosen to display it in the promotion of your product implies FDA approval or sanction of your product and its purported uses and thus could cause your product to be misbranded under section 403(a)(1). We request that you remove the pictures of the FDA seal from your web site.
FDA Refuses Entry to a Shipment of Organic Germanium Destined for Vibrant Life
On May 12, 2005 the FDA refused entry to a shipment of organic germanium destined for Vibrant Life under the product adulteration charge. According to owner Karl Loren, the product’s origin is Tokai Sangyo Japan.
Vibrant Life
Burbank, CA 91504-1908 CIN-DO 110-0771924-2/1/1
54YCE09 Organic Germanium
12-MAY-2005 UNSFDIETLB
Reason: UNSFDIETLB
Section: 402(f)(1)(A), 801(a)(3) Adulteration
Charge: The article appears to be a dietary supplement or
ingredient that represents a significant or unreasonable
risk of illness or injury under customary conditions of use.
Record of Vibrant Life Product Refusal (Approximately pg. 12)
http://www.fda.gov/ora/oasis/5/ora_oasis_c_us.html
(Approximately pg. 29)
http://www.fda.gov/ora/oasis/5/ora_oasis_i_54.html
Violation Code Against Vibrant Life
Violation Code against Vibrant Life
http://www.fda.gov/ora/oasis/ora_oasis_viol.html#2460
As a matter of public record, Vibrant Life also received a warning letter from the FDA back in October of 2000 for unlawful product claims and marketing what FDA considered unapproved drugs. This warning letter was for Vibrant Life’s MSM products but still establishes a point of reference as to marketing tactics that portray the entire industry a bad light. This is one company that insists no import alert for germanium exists.
http://www.fda.gov/cder/warn/cyber/oct2000/cyber034.pdf
FDA Cites Deaths Associated with Germanium Products
In 1993, the FDA published an article entitled "Unsubstantiated Claims and Documented Health Hazards in the Dietary Supplement Marketplace.” Under a section entitled "Illnesses and Injuries Associated With the Use of Selected Dietary Supplements". Germanium is targeted in a “list of selected dietary supplements associated with serious safety problems”. This was on account of contamination problems encountered with Aisian sources of organic germanium that caused acute renal failure and even some deaths.
A. Germanium
Germanium is a nonessential element. Recently, germanium has been marketed in the form of inorganic germanium salts and novel organogermanium compounds, as a "dietary supplement." These products are promoted for their claimed immunomodulatory effects or as "health-promoting" elixirs. Germanium supplements, when used chronically, have caused nephrotoxicity (kidney injury) and death. Since 1982, there have been 20 reported cases of acute renal failure, including two deaths, attributed to oral intakes of germanium elixirs. In surviving patients, kidney function has improved after discontinuation of germanium, but none of the patients have recovered normal kidney function.
One particular organogermanium compound, an azaspiran organogermanium, has been studied for its potential use as an anticancer drug. Forty percent of the patients in this study experienced transient neurotoxicity (nerve damage), and two patients developed pulmonary toxicity. Because of these side effects, medically supervised administration of this drug with monitoring for toxicity has been recommended for those using germanium chronically. http://www.cfsan.fda.gov/~dms/ds-ill.html
U.S. Manufactured Germanium Sesquioxide
Background:
From the mid to late 1980s, contaminated Germanium Sesquioxide imported from Asia reportedly caused numerous cases of renal failure and even some deaths. This was driven mainly by sloppy process controls, the actions of unscrupulous profiteers, and ignorance on the part of consumers and scientists alike. Different sources of germanium often failed to correctly distinguish between safe organic forms and inorganic forms reported to cause the problem.
Large quantities of Bis (2-carboxyethylgermanium sesquioxide), more commonly known as Germanium Sesquioxide, have been manufactured in Utah since 1987 Why is this so important to the nutritional industry? An established domestic source offers several advantages to the consumer.
Quality:
Designed Nutritional's Germanium Sesquioxide is manufactured under well established process controls to strict product specifications. In addition to raw material qualification and in-process testing, each completed batch of material is subjected to numerous analytical tests to positively establish the identity, consistency, and purity. Such rigorous controls are time consuming and costly, but have paid huge dividends by way of a perfect safety track record for nearly two decades.
How do we effectively compete against foreign sources with U.S. manufactured Germanium Sesquioxide that meets or exceeds the quality of anything else out there? Over the years, a dedicated team of PHD chemists, Engineers, scientists, and skilled technicians have optimized the manufacturing process owned by Designed Nutritional Products. This enables us to capitalize on superior technology and economies of scale without compromising quality. This level of expertise also enables us to provide uncommon technical support.
Technical Support:
Designed Nutritional provides a comprehensive certificate of analysis with every shipment of Germanium Sesquioxide and is able to supply all testing methods upon request. Additionally, years of hands on experience, an extensive research library, and educational seminars all combine to provide a level of technical support not easily surpassed.
Legal:
Import restrictions prevent Germanium Sesquioxide from legally entering the country but not from being sold. The FDA issued an import alert against Germanium products in 1988 and again in 1995 This import alert is still in force today. This is primarily the result of the deleterious effects caused by contaminated material being imported from Asia. In spite of this action, material continues to slip across the border. The FDA aggresively enforces this import alert. However, unscrupulous profiteers are engaged in gross negligence or fraud in order to sneak it through customs. Designed Nutritional's domestic product is the best way to insure a legal supply.
False Allegation that no Domestic Source Exists:
The individual making this allegation is trying to compete in the U.S. market with Germanium Sesquioxide imported from Japan, in spite of import restrictions that prevent him from legally doing so. The claim that no domestic supply for Germanium Sesquioxide exists is utter nonsense driven either by extreme naiveté or malicious jealousy. Designed Nutritional's technology has been used in Utah since 1987 to manufacture large quantities of Germanium Sesquioxide each year. Designed Nutritional is the only domestic source that we're aware of.
Designed Nutritional stands behind its Made in the USA claim for Germanium Sesquioxide and will back any customer wishing to benefit from the quality and value this claim carries.
Import Alert is not Cancelled:
I found the import restriction for Germanium Sesquioxide you referred to, but it appears to be cancelled. Please Explain
The import restriction against Germanium Sesquioxide has not been cancelled. It clearly states that an earlier alert issued in 1988 was cancelled, for the purpose of revision, with the simultaneous issuance of another in 1995. This fact was verified as recently as May 2005 by an FDA compliance officer. This import alert further states that germanium material can be seized if the intended purpose is for human consumption and lists various names under which someone may attempt to bring ingestible germanium into the country. In cases like this, a simple LD 50 is not considered sufficient evidence in support of lifting the import restrictions. Designed Nutritional reaffirms its earlier position that any US importer of Germanium Sesquioxide is violating import restrictions that prevent the product from entering legally. http://www.fda.gov/ora/fiars/ora_import_ia5407.html.
Truth in Labeling for Retailers
What regulations govern label claims for US manufactured Organic Germanium?
Designed Nutritional Products supports both truth in advertising and truth in labeling. We abide by FTC and FDA label regulations, and we encourage our customers to follow the same industry standards.
Designed Nutritional stands behind its Made in the USA claim for Germanium Sesquioxide and will back any customer wishing to benefit from the quality and value this claim carries.
Designed Nutritional encourages all of our germanium customers to use the Made in the USA claim on their retail labels, so as to distinguish US product from illegitimate sources.
Peer Reviewed Articles on Germanium Sesquioxide
J Altern Complement Med. 2004 Apr;10(2):337-44.
Germane Facts About Germanium Sesquioxide:
I. Chemistry and Anticancer Properties
Kaplan BJ, Parish WW, Andrus GM, Simpson JS, Field CJ.
The Journal of Alternative & Complementary Medicine. 1 April 2004, vol. 10, no. 2, pp. 337-344(8) Kaplan B.J.[1]; Parish W.W.[2]; Andrus G.M.[3]; Simpson J.S.A.[4]; Field C.J.[5]
Departments of Pediatrics, and Community Health Sciences, Faculty of Medicine, University of Calgary, and Alberta Children's Hospital, Calgary, Alberta, Canada. kaplan@ucalgary.ca.
This paper reviews the history, chemistry, safety, toxicity, and anticancer effects of the organogermanium compound bis (2-carboxyethylgermanium) sesquioxide (CEGS). A companion review follows, discussing the inaccuracies in the scientific record that have prematurely terminated research on clinical uses of CEGS. CEGS is a unique organogermanium compound first made by Mironov and coworkers in Russia and, shortly thereafter, popularized by Asai and his colleagues in Japan. Low concentrations of germanium occur in nearly all soils, plants and animal life; natural occurrence of the CEGS form is postulated but not yet demonstrated. The literature demonstrating its anticancer effect is particularly strong: CEGS induces interferon-gamma (IFN-gamma), enhances natural killer cell activity, and inhibits tumor and metastatic growth--effects often detectable after a single oral dose. In addition, oral consumption of CEGS is readily assimilated and rapidly cleared from the body without evidence of toxicity. Given these findings, the absence of human clinical trials of CEGS is unexpected. Possible explanations of why the convincing findings from animal research have not been used to support clinical trials are discussed. Clinical trials on CEGS are recommended.
Publication Types:
• Review
• Review, Tutorial
PMID: 15165414 [PubMed - indexed for Abstract 15165414 MEDLINE]
JAltern Complement Med. 2004 Apr;10(2):345-8.
Germane Facts About Germanium Sesquioxide:
II. Scientific Error and Misrepresentation.
Kaplan BJ, Andrus GM, Parish WW.
Departments of Pediatrics, and Community Health Sciences, Faculty of Medicine, University of Calgary, and Alberta Children's Hospital, Calgary, Alberta, Canada. kaplan@ucalgary.ca
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.
Publication Types:
• Review
• Review, Tutorial
PMID: 15165415 [PubMed - indexed for Abstract 15165415 MEDLINE]
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Why is There Conflicting Information on Germanium Safety?
Germanium Sesquioxide: Safer Than Table Salt
To The Editor,
I am troubled by a recent article published in The Natural Foods Merchandiser's "Behind the Label" magazine. The article was titled "Finding Information on Troubled Herbs" and stated: "Retailers are discouraged from selling germanium, for example, because of problems with toxic contamination in its manufacture."
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.
Domestic Supply for Germanium Sesquioxide Exists
I keep hearing that no domestic supply for Germanium Sesquioxide exists. Is this accurate?
The claim that no domestic supply exists is utter nonsense driven either by extreme naiveté or malicious jealousy. Designed Nutritional’s technology has been used in Utah since 1987 to manufacture large quantities of Germanium Sesquioxide. We are the only domestic source that I am aware of.
Designed Nutritional stands behind its Made in the USA claim for Germanium Sesquioxide and will back any customer wishing to benefit from the quality and value this claim carries.
Is Germanium Sesquioxide Legal?
I've heard that Germanium Sesquioxide is illegal. What can you tell me about this?
There is nothing illegal about a domestic supply. However, the FDA issued an import alert against Germanium products in 1988 and again in 1995. This import alert is still in force today. This action was driven primarily by the deleterious effects of contaminated material being imported from Asia. In spite of this action, material continues to slip across the border (apparently illegally). The most common names are targeted which suggests that un-scrupled profiteers are engaged in gross negligence or fraud in order to sneak it through customs. Designed Nutritional’s domestic product is the best way to insure a reliable and legal supply. http://www.fda.gov/ora/fiars/ora_import_ia5407.html.
Price Disparity for Bulk Germanium Sesquioxide Source
There is a huge price disparity for bulk Germanium Sesquioxide. Some material is being sold as low as $800/kg and some as high as $6000/kg. What is the difference?
This is one product where higher price does not directly correlate with higher quality. There are a number of good sources in addition to analytical testing methods for quality screening. In the past years we have identified good material from numerous competing sources, including China. Keep in mind that contaminated Asian material is largely responsible for the tainted image of Germanium Sesquioxide today. Import restrictions also call into question the legality of bringing any foreign source into the country. It’s been years since Designed Nutritional screened the competition so I cannot vouch for consistent quality from any source other than Designed Nutritional’s U.S. manufactured product.
Material costs and labor are the primary drivers for price. Good manufacturing technology plays a more minor role. However, the price of $6,000/ kg for bulk Germanium Sesquioxide is awful hard to justify under any circumstances. I’m aware of one such source and it blows my mind that anyone can feel good about selling imported Asian Germanium Sesquioxide for such an outrageous price, especially when this vendor admittedly cannot distinguish his product from a mixture of Vitamin C and germanium dioxide. This is a terrifying confession in my opinion.
The price for bulk U.S. manufactured material is $1,340 - $1,500/kg. Since the cost of materials and labor is much higher in the U.S., all foreign material should easily compete with any U.S. price. My guess is that Asian material is originally acquired for under $1,000 which means that $6,000/kg is pure highway robbery. My advice is to keep your wallet in your pocket and your house locked.