Prized for its luster, purity, and value, gold may be the first metal used by humans. In its raw form, it appears more like a dark yellow rock. The first known health-related use of gold was recorded by the ancient Egyptians approximately 4500 years ago.1 Gold dental work has been found in archeologic sites, indicating that the Egyptians mined, extracted, and shaped the mineral for a wide variety of uses in their civilization. Modern use of gold in medicine began in the early 1900s and was referred to as aurotherapy or chrysotherapy.2
Background
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Gold is classified as a metal, with the elemental designation of Au. It has a density of nearly 20 g/cm3 and does not melt until it reaches an amazing 1948 degrees Fahrenheit.3 Because of its purity, gold is an inert element when used in the human body. This biocompatibility has made it extremely useful in many areas of dentistry and medicine. Anti-inflammatory and antimicrobial actions have since been widely recognized.
Science
The anti-inflammatory mechanism of gold compounds is still one of speculation, but mounting evidence indicates that gold is taken into intracellular organelles and stored in lysosomes. There, it both inhibits the processing of antigenic agents and blocks the reactive processes that produce and release inflammatory cytokines.4,5 Research that was originally directed at the use of gold in rheumatoid arthritis evolved to show potential uses in antimicrobial therapy as well as antiviral therapy. Ongoing studies exploring the use of gold in the treatment of conditions such as cancer and human immunodeficiency virus show promising potential.
Even though the use of gold products to treat rheumatoid arthritis has declined since the development of newer anti-inflammatory agents and biologic disease-modifying antirheumatic drugs (DMARDs), its efficacy still appeals to many. In a systematic review of the gold drug auranofin versus placebo for the treatment of rheumatoid arthritis, the gold compound was more efficacious when patient outcomes were scored on the presence of tender joints, pain, and erythrocyte sedimentation rate.6
In a 48-week randomized, placebo-controlled trial, researchers examined the results of using both oral methotrexate and intramuscular gold therapy in patients with rheumatoid arthritis whose disease was not sufficiently controlled on methotrexate alone. The researchers reported significant clinical improvement after adding intramuscular gold therapy to methotrexate.7
The same mechanisms of action are being explored for possible anticancer and antimicrobial actions. Gold microparticles in a cancer cell appear to accelerate cell death as well as upregulate tumor-suppressing signals.8 Gold has also been shown to both inhibit cell growth of certain infectious microbes and make these cells more susceptible to oxidative stress and death.9 Laboratory researchers have demonstrated that relatively low intracellular concentrations of gold microparticles exhibit definite inhibitory action against cultures of methicillin-resistant Staphylococcus aureus.10
Safety, interactions, side effects
The use of gold therapy is centuries old. However, there are significant side effects associated with the long-term use of parenteral gold products, and the list of organ systems subject to damage by gold therapy is lengthy. Nephropathy, lung damage, and liver injury are well-established adverse effects of long-term gold therapy.11
How supplied, dose
Gold therapy should never be used without ongoing monitoring by a healthcare professional who is experienced in the use of gold products. Currently, oral and intramuscular gold therapy are available by prescription.
Summary
The reassessment of an old therapy is not new in medicine, and the future of gold therapy looks bright. Increasing bacterial resistance to antibiotics has added energy to medical science’s ever-expanding search for antibacterial and antiviral therapies. In addition, the use of gold therapy as an anticancer agent appears promising, as does its more common use as a DMARD.
References
- Purest Colloids. A Brief History of the Health Support Uses of Gold. https://www.purestcolloids.com/history-gold.php.
- Shaw CF III. Gold-based therapeutic agents. Chem Rev. 1999;99(9):2589-2600.
- Royal Society of Chemistry. Periodic Table. Gold. http://www.rsc.org/periodic-table/element/79/gold.
- Seifert O, Matussek A, Sjögren F, Geffers R, Anderson CD. Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions. J Inflamm (Lond). 2012;9(1):43.
- Rigobello MP, Folda A, Baldoin MC, Scutari G, Bindoli A. Effect of auranofin on the mitochondrial generation of hydrogen peroxide: role of thioredoxin reductase. Free Radic Res. 2005;39(7):687-695.
- Suarez-Almazor ME, Spooner CH, Belseck E, Shea B. Auranofin versus placebo in rheumatoid arthritis. Cochrane Database Syst Rev. 2000;(2):CD002048.
- Lehman AJ, Esdaile JM, Klinkhoff AV, Grant E, Fitzgerald A, Canvin J. A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study. Arthritis Rheum. 2005;52(5):1360-1370.
- Park SH, Lee JH, Berek JS, Hu MC. Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53. Int J Oncol. 2014;45(4):1691-1698.
- Harbut MB, Vilchèze C, Luo X, et al. Auranofin exerts broad-spectrum bactericidal activities by targeting thiol-redox homeostasis. Proceedings Natl Acad Sci U.S.A. 2015;112(14):4453-4458.
- Hokai Y, Jurkowicz B, Fernández-Gallardo J, et al. Auranofin and related heterometallic gold(I)–thiolates as potent inhibitors of methicillin-resistant Staphylococcus aureus bacterial strains. J Inorg Biochem. 2014;138:81-88.
- Klinkhoff A. Major side effects of gold therapy. UpToDate. http://www.uptodate.com/contents/major-side-effects-of-gold-therapy. Updated March 22, 2016.
All electronic documents accessed July 14, 2016.
