Of the many trace elements, germanium is one that we all naturally encounter each and every day; yet many healthcare practitioners have limited knowledge of it. Organic germanium is found at trace amounts in many foods, and the dietary intake of it has been estimated to be between 0.4 to 3.4 mg daily.1 It is found at higher levels in substances like potato, carrot, cereals, meats, fish, shellfish, garlic, ginseng, and aloe vera.2,3 Low levels of germanium have been shown to exist in the nails, hair, urine, and plasma of healthy humans,4 at comparable levels to those of other trace elements such as strontium, manganese, and lithium.1
Much like these other trace or ultra-trace elements, organic germanium has been shown in numerous studies to have a positive effect on health, which will be reviewed herein. Germanium is found in mineral waters in Japan, Korea, and regions of Europe touted for their healing benefits; and certain “curative” natural springs are also high in germanium.5 The first records of its use date back to the 1960s in Russia and Japan—documented in the writings of Mironov of Russia and Dr. Asai of Japan6,7—and we still see much research coming from these regions.
One item of crucial importance to note before further discussion of germanium’s biological effects is the difference between organic germanium—also known as bis (2-carboxyethylgermanium) sesquioxide (CEGS), germanium sesquioxide, or Ge-132—and inorganic germanium (typically germanium dioxide, but also existing as germanium citrate lactate).8 While Ge-132 is extremely safe,9 inorganic germanium compounds are not, and are highly toxic, particularly to the kidneys.10 Numerous deaths due to renal failure have been reported with long-term ingestion of inorganic germanium compounds.11 Additional symptoms that may occur with the consumption of inorganic germanium products are largely gastrointestinal and may include vomiting, anorexia, and weight loss.
The safety of organic germanium is highlighted in a 2020 publication that reviewed the outcomes of a battery of standardized toxicology tests.9 Outcomes of many historic tests prior to these have been critiqued because the quality of organic germanium products were not verified, so low levels of inorganic germanium may have existed. Proper testing of organic germanium products is important to confirm that inorganic impurities do not exist.
The findings of the comprehensive 2020 review were that ≥99.6% pure Ge-132 with less than <50 ppm germanium dioxide was safe in rats when consumed for 90 days at a dose up to 2,000 mg/kg/day.9 Additionally, genetic toxicology studies found that mutagenic, chromosomal, or in vivo genotoxic potential under the applied test systems was not seen up to the maximum recommended test concentrations or limit dose.
Immunoenhancer
One quality of Ge-132 leading to its clinical use is its action as an immunostimulant. Genetic assessment has shown that the greatest impact of Ge-132 is on immune activation, with the expression of more than 60 genes being affected by its intake.12 Specifically, Ge-132 has been shown to augment the immune response by enhancing natural killer (NK) cell activity and increasing interferon (IFN)-γ.13 Multiple studies have shown these effects, with a peak IFN-γ response occurring at 24 hours. Ge-132 has also been shown to attenuate immunosuppression due to physical stressors such as surgery or heat, enhancing IFN-γ and/or NK activity in these settings as well.14,15 In animals subject to typically lethal viral infections, administration of Ge-132 increased the survival rate, prolonged survival time, and decreased viral titers and organ complications.16
Findings such as these have prompted investigations in settings of malignancy, where healthy immune surveillance and NK cell activity is paramount. In animals with malignancy, Ge-132 has also been shown to increase IFN-γ levels and NK activity.17,18 Additionally, when given as an adjunctive to the chemotherapeutic agents 5-fluorouracil and bleomycin, it enhanced their anti-tumor effects, increased animal survival, and decreased the treatment-related loss of weight.19 Clinically, increased NK activity has also been seen with the use of Ge-132 at a dose of 1000 mg/day in patients with cancer, with an optimal response observed with intermittent (rather than daily) dosing.20
These immunostimulating effects have also led the study of germanium as an agent to improve the effectivity of vaccinations. In multiple animal studies, germanium was shown to increase the vaccine response.21,22 Additionally, when it was applied as a monotherapy, it enhanced the immune response in a similar fashion.
A Panacea of Actions
The antioxidant effects of organic germanium have also been investigated in numerous cellular and animal models. In cell studies, Ge-132 has been shown to protect cells from oxidative stress induced by hydrogen peroxide;23 in oocytes, it increases intracellular glutathione and reduces levels of reactive oxygen species;24 and in animals, it decreases low-density lipoprotein oxidation,25 increases α-tocopherol levels,12 and protects the liver from chemically induced oxidative injury, enhancing levels of antioxidant enzymes.26
In vitro, Ge-132 has been shown to increase cellular ATP levels;23 analysis of its effects on genetic expression also suggests this.12 Positive outcomes seen with Ge-132 in patients with chronic fatigue syndrome have been attributed to its immune-enhancing effects27; however, this was prior to the more recent findings related to ATP.
Finally, interesting effects of germanium on calcification and wound healing have been seen. In hens, eggshell (primarily composed of CaCO3) strength has been increased by the addition of germanium to the feed.28 Germanium supplementation has been shown to increase bone strength in ovariectomized animals.29,30 It is even being investigated as a material to alloy with magnesium for biodegradable orthopedic implants.1 In cellular and in vivo wound-healing studies, treatment with Ge-132 has been shown to significantly improve the wound-healing rate, specifically increasing fibroblast proliferation and formation of collagen fibers, and decreasing edema.31
Clearly, Ge-132 is a mineral with interesting and varied biological effects whose reputation has been tarnished due to the adverse effects of its closely related peer, inorganic germanium.8 With a higher level of scrutiny of the purity of Ge-132—which scientific advancements since its discovery have enabled—we will undoubtedly continue to see an increasing interest in its research and use in human health.
References
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