Medical uses of silver#Mechanism of action

Silver and most silver compounds have an oligodynamic effect and are toxic for bacteria, algae, and fungi in vitro. The antibacterial action of silver is dependent on the silver ion. The effectiveness of silver compounds as an antiseptic is based on the ability of the biologically active silver ion ({{chem|Ag|+}}) to irreversibly damage key enzyme systems in the cell membranes of pathogens. The antibacterial action of silver has long been known to be enhanced by the presence of an electric field. Applying an electric current across silver electrodes enhances antibiotic action at the anode, likely due to the release of silver into the bacterial culture.{{cite journal | vauthors = Spadaro JA, Berger TJ, Barranco SD, Chapin SE, Becker RO | title = Antibacterial effects of silver electrodes with weak direct current | journal = Antimicrobial Agents and Chemotherapy | volume = 6 | issue = 5 | pages = 637–42 | date = November 1974 | pmid = 15825319 | pmc = 444706 | doi = 10.1128/AAC.6.5.637 }} The antibacterial action of electrodes coated with silver nanostructures is greatly improved in the presence of an electric field.{{cite journal | vauthors = Akhavan O, Ghaderi E | title = Enhancement of antibacterial properties of Ag nanorods by electric field | journal = Science and Technology of Advanced Materials | volume = 10 | issue = 1 | pages = 015003 | date = February 2009 | pmid = 27877266 | pmc = 5109610 | doi = 10.1088/1468-6996/10/1/015003 | bibcode = 2009STAdM..10a5003A }}

Silver, used as a topical antiseptic, is incorporated by bacteria it kills. Thus dead bacteria may be the source of silver that may kill additional bacteria.{{cite journal | vauthors = Wakshlak RB, Pedahzur R, Avnir D | title = Antibacterial activity of silver-killed bacteria: the "zombies" effect | journal = Scientific Reports | volume = 5 | pages = 9555 | date = April 2015 | pmid = 25906433 | pmc = 5386105 | doi = 10.1038/srep09555 | bibcode = 2015NatSR...5.9555W}}

{{see also|Silver sulfadiazine}}

Silver sulfadiazine (SSD) is a topical antibiotic used in partial thickness and full thickness burns to prevent infection.{{cite book| vauthors = Marx J, Walls R, Hockberger R |title=Rosen's Emergency Medicine - Concepts and Clinical Practice|date=2013|publisher=Elsevier Health Sciences|isbn=978-1455749874|page=814|url=https://books.google.com/books?id=uggC0i_jXAsC&pg=PA814|language=en|url-status=live|archive-url=https://web.archive.org/web/20160913112905/https://books.google.ca/books?id=uggC0i_jXAsC&pg=PA814|archive-date=2016-09-13}} It was discovered in the 1960s,{{cite book| vauthors = Coran AG, Caldamone A, Adzick NS, Krummel TM, Laberge JM, Shamberger R |title=Pediatric Surgery|date=2012|publisher=Elsevier Health Sciences|isbn=978-0323091619|page=369|edition=7|url=https://books.google.com/books?id=QpabASTwF_sC&pg=PA369|language=en|url-status=live|archive-url=https://web.archive.org/web/20160913123107/https://books.google.ca/books?id=QpabASTwF_sC&pg=PA369|archive-date=2016-09-13}} and was the standard topical antimicrobial for burn wounds for decades.{{cite journal | vauthors = Adhya A, Bain J, Ray O, Hazra A, Adhikari S, Dutta G, Ray S, Majumdar BK | display-authors = 6 | title = Healing of burn wounds by topical treatment: A randomized controlled comparison between silver sulfadiazine and nano-crystalline silver | journal = Journal of Basic and Clinical Pharmacy | volume = 6 | issue = 1 | pages = 29–34 | date = December 2014 | pmid = 25538469 | pmc = 4268627 | doi = 10.4103/0976-0105.145776 | doi-access = free }}{{cite journal | vauthors = Gomes MT, Campos GR, Piccolo N, França CM, Guedes GH, Lopes F, Belotto RA, Pavani C, Lima RD, Silva DF | display-authors = 6 | title = Experimental burns: Comparison between silver sulfadiazine and photobiomodulation | journal = Revista da Associação Médica Brasileira | volume = 63 | issue = 1 | pages = 29–34 | date = January 2017 | pmid = 28225874 | doi = 10.1590/1806-9282.63.01.29 | doi-access = free }}

However systemic reviews in 2014, 2017 and 2018 concluded that more modern treatments, both with and without silver, show better results for wound healing and infection-prevention than silver sulfadiazine,{{cite journal | vauthors = Rashaan ZM, Krijnen P, Klamer RR, Schipper IB, Dekkers OM, Breederveld RS | title = Nonsilver treatment vs. silver sulfadiazine in treatment of partial-thickness burn wounds in children: a systematic review and meta-analysis | journal = Wound Repair and Regeneration | volume = 22 | issue = 4 | pages = 473–482 | year = 2014 | pmid = 24899251 | doi = 10.1111/wrr.12196 | s2cid = 19224002 }}{{cite journal | vauthors = Nherera LM, Trueman P, Roberts CD, Berg L | title = A systematic review and meta-analysis of clinical outcomes associated with nanocrystalline silver use compared to alternative silver delivery systems in the management of superficial and deep partial thickness burns | journal = Burns | volume = 43 | issue = 5 | pages = 939–948 | date = August 2017 | pmid = 28161149 | doi = 10.1016/j.burns.2017.01.004 }}{{cite journal | vauthors = Nímia HH, Carvalho VF, Isaac C, Souza FÁ, Gemperli R, Paggiaro AO | title = Comparative study of Silver Sulfadiazine with other materials for healing and infection prevention in burns: A systematic review and meta-analysis | journal = Burns | volume = 45 | issue = 2 | pages = 282–292 | date = March 2019 | pmid = 29903603 | doi = 10.1016/j.burns.2018.05.014 | hdl-access = free | hdl = 11449/171102 | s2cid = 49215672 }} and therefore SSD is no longer generally recommended.{{cite journal | vauthors = Wasiak J, Cleland H, Campbell F, Spinks A | title = Dressings for superficial and partial thickness burns | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 3 | pages = CD002106 | date = March 2013 | pmid = 23543513 | pmc = 7065523 | doi = 10.1002/14651858.CD002106.pub4 | quote = It is impossible to draw firm and confident conclusions about the effectiveness of specific dressings, however silver sulphadiazine was consistently associated with poorer healing outcomes than biosynthetic, silicon-coated and silver dressings whilst hydrogel-treated burns had better healing outcomes than those treated with usual care. }}{{cite journal | vauthors = Heyneman A, Hoeksema H, Vandekerckhove D, Pirayesh A, Monstrey S | title = The role of silver sulphadiazine in the conservative treatment of partial thickness burn wounds: A systematic review | journal = Burns | volume = 42 | issue = 7 | pages = 1377–1386 | date = November 2016 | pmid = 27126813 | doi = 10.1016/j.burns.2016.03.029 | hdl-access = free | hdl = 1854/LU-8507323 }}

It is on the World Health Organization's List of Essential Medicines.{{cite book | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free | last1 = Organization | first1 = World Health }} The US Food and Drug Administration (FDA) approved a number of topical preparations of silver sulfadiazine for treatment of second-degree and third-degree burns.{{cite web|url=http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm?fuseaction=Search.DrugDetails|title=Drugs@FDA|publisher=U.S. Food and Drug Administration (FDA)|access-date=2010-07-10|archive-url=https://web.archive.org/web/20140813131107/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails|archive-date=2014-08-13|url-status=dead}}

Despite its widespread use, there is only mixed evidence that silver in dressings has any benefit.{{cite journal |vauthors=May A, Kopecki Z, Carney B, Cowin A |title=Antimicrobial silver dressings: a review of emerging issues for modern wound care |journal=ANZ J Surg |volume=92 |issue=3 |pages=379–384 |date=March 2022 |pmid=34806300 |doi=10.1111/ans.17382 |s2cid=244477692 |type=Review}} A 2018 Cochrane review found that silver-containing dressings may increase the probability of healing for venous leg ulcers.{{cite journal | vauthors = Norman G, Westby MJ, Rithalia AD, Stubbs N, Soares MO, Dumville JC | title = Dressings and topical agents for treating venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | pages = CD012583 | date = June 2018 | issue = 6 | pmid = 29906322 | pmc = 6513558 | doi = 10.1002/14651858.CD012583.pub2 }}

A number of wound dressings containing silver as an anti-bacterial have been cleared by the U.S. Food and Drug Administration (FDA).Ethicon, Inc. [http://www.accessdata.fda.gov/cdrh_docs/pdf2/K022483.pdf "510(k) Summary for K022483"]. Food and Drug Administration (February 3, 2003).[http://www.accessdata.fda.gov/cdrh_docs/pdf2/K023609.pdf 510(k) "Summary for K023609]". Argentum Medical LLC (January 17, 2003).[http://www.accessdata.fda.gov/cdrh_docs/pdf5/K050032.pdf 510(k) "Summary for K050032"] Euromed (May 17, 2005).[http://www.accessdata.fda.gov/cdrh_docs/pdf5/K053627.pdf "510(k) Summary for K053627"]. Kinetic Concepts (February 6, 2006). However, silver-containing dressings may cause staining, and in some cases tingling sensations as well.{{Cite web|title=Silver Antimicrobial Dressings in Wound Management: A Comparison of Antibacterial, Physical, and Chemical Characteristics|url=https://www.woundsresearch.com/article/4543|access-date=2021-02-18|website=Wounds Research|language=en}}

A 2015 systematic review concluded that the limited evidence available indicates that using silver-coated endotracheal breathing tubes reduces the risk of contracting ventilator-associated pneumonia (VAP), especially during the initial days of utilisation.{{cite journal | vauthors = Tokmaji G, Vermeulen H, Müller MC, Kwakman PH, Schultz MJ, Zaat SA | title = Silver-coated endotracheal tubes for prevention of ventilator-associated pneumonia in critically ill patients | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD009201 | date = August 2015 | volume = 2015 | pmid = 26266942 | doi = 10.1002/14651858.CD009201 | pmc = 6517140 | veditors = Tokmaji G }} A 2014 study concluded that using silver-coated endotracheal tubes will help to prevent VAP and that this may save on hospital costs.{{cite journal | vauthors = Shorr AF, Zilberberg MD, Kollef M | title = Cost-effectiveness analysis of a silver-coated endotracheal tube to reduce the incidence of ventilator-associated pneumonia | journal = Infection Control and Hospital Epidemiology | volume = 30 | issue = 8 | pages = 759–763 | date = August 2009 | pmid = 19538095 | doi = 10.1086/599005 | s2cid = 14809364 | url = https://digitalcommons.wustl.edu/open_access_pubs/820 }} A 2012 systematic review of randomized controlled trials concluded that the limited evidence available indicates that using silver-coated endotracheal tubes will reduce the incidence of ventilator-associated pneumonia, microbiologic burden, and device-related adverse events among adult patients.{{cite journal | vauthors = Li X, Yuan Q, Wang L, Du L, Deng L | title = Silver-coated endotracheal tube versus non-coated endotracheal tube for preventing ventilator-associated pneumonia among adults: a systematic review of randomized controlled trials | journal = Journal of Evidence-Based Medicine | volume = 5 | issue = 1 | pages = 25–30 | date = February 2012 | pmid = 23528117 | doi = 10.1111/j.1756-5391.2012.01165.x | s2cid = 23720955 }} Another 2012 review agreed that the use of silver-coated endotracheal tubes reduces the prevalence of VAP in intubated patients, but cautioned that this on its own is not sufficient to prevent infection. They also suggested that more research is needed to establish the cost-effectiveness of the treatment.{{cite journal | vauthors = Kane T, Claman F | title = Silver tube coatings in pneumonia prevention | journal = Nursing Times | volume = 108 | issue = 36 | pages = 21–23 | year = 2012 | pmid = 23035371 }} Another 2012 study agreed that there is evidence that endotracheal tubes coated with silver may reduce the incidence of ventilator associated pneumonia (VAP) and delay its onset, but concluded that no benefit was seen in the duration of intubation, the duration of stay in intensive care or the mortality rate. They also raised concerns surrounding the unblinded nature of some of the studies then available.

The U.S. Food and Drug Administration in 2007 cleared an endotracheal tube with a fine coat of silver to reduce the risk of ventilator-associated pneumonia.{{cite web|url= https://www.fda.gov/bbs/topics/NEWS/2007/NEW01741.html| title= FDA Clears Silver-Coated Breathing Tube For Marketing| publisher = Food and Drug Administration|date= 2007-11-08|archive-url=https://web.archive.org/web/20071114040503/https://www.fda.gov/bbs/topics/NEWS/2007/NEW01741.html|archive-date=November 14, 2007}}

A 2014 systemic review concluded that using silver alloy-coated catheters showed no significant difference in incidences of symptomatic Catheter-Associated Urinary Tract Infections (CAUTI) versus using standard catheters, although silver-alloy catheters seemed to cause less discomfort to patients.{{cite journal | vauthors = Lam TB, Omar MI, Fisher E, Gillies K, MacLennan S | title = Types of indwelling urethral catheters for short-term catheterisation in hospitalised adults | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD004013 | date = September 2014 | pmid = 25248140 | doi = 10.1002/14651858.CD004013.pub4 | pmc = 11197149 }} These catheters are associated with greater cost than other catheters. A 2014 Multicenter Cohort Study found that using a silver-alloy hydrogel urinary catheter did reduce symptomatic Catheter-Associated Urinary Tract Infection (CAUTI) occurrences as defined by both NHSN and clinical criteria. A 2011 critical analysis of eight studies found a consistent pattern which supported using silver-alloy urinary catheters over uncoated catheters to reduce infections in adult patients, and concluded that using silver-alloy catheters would significantly improve patient care. A 2007 systemic review concluded that using silver-alloy indwelling catheters for short-term catheterizing will reduce the risk of catheter-acquired urinary tract infection, but called for further studies to evaluate the economic benefits of using the expensive silver alloy-catheters. Two systemic reviews in 2004 found that using silver-alloy catheters reduced asymptomatic and symptomatic bacteriuria more than standard catheters, for patients who were catheterised for a short time.{{cite journal | vauthors = Rosier PK | title = Review: silver alloy catheters are more effective than standard catheters for reducing bacteriuria in adults in hospital having short term catheterisation | journal = Evidence-Based Nursing | volume = 7 | issue = 3 | pages = 85 | date = July 2004 | pmid = 15252913 | doi = 10.1136/ebn.7.3.85 | s2cid = 35670327 | url = http://ebn.bmj.com/cgi/content/short/7/3/85 | doi-access = free }} A 2000 randomized crossover study found that using the more expensive silver-coated catheter may result in cost savings by preventing nosocomial UTI infections,{{cite journal | vauthors = Karchmer TB, Giannetta ET, Muto CA, Strain BA, Farr BM | title = A randomized crossover study of silver-coated urinary catheters in hospitalized patients | journal = Archives of Internal Medicine | volume = 160 | issue = 21 | pages = 3294–3298 | date = November 2000 | pmid = 11088092 | doi = 10.1001/archinte.160.21.3294 | doi-access = free }} and another 2000 study found that using silver alloy catheters for short-term urinary catheterization reduces the incidence of symptomatic UTI and bacteremia compared with standard catheters, and may thus yield cost savings.{{cite journal | vauthors = Saint S, Veenstra DL, Sullivan SD, Chenoweth C, Fendrick AM | title = The potential clinical and economic benefits of silver alloy urinary catheters in preventing urinary tract infection | journal = Archives of Internal Medicine | volume = 160 | issue = 17 | pages = 2670–2675 | date = September 2000 | pmid = 10999983 | doi = 10.1001/archinte.160.17.2670 | doi-access = free }}

A 2017 study found that a combination of chlorhexidine and silver-sulfadiazine (CSS) used to coat central venous catheters (CVC) reduces the rate of catheter-related bloodstream infections.{{cite journal | vauthors = Choi YJ, Lim JK, Park JJ, Huh H, Kim DJ, Gong CH, Yoon SZ | title = Chlorhexidine and silver sulfadiazine coating on central venous catheters is not sufficient for protection against catheter-related infection: Simulation-based laboratory research with clinical validation | journal = The Journal of International Medical Research | volume = 45 | issue = 3 | pages = 1042–1053 | date = June 2017 | pmid = 28534703 | pmc = 5536400 | doi = 10.1177/0300060517708944 }} However, they also found that the efficacy of the CSS-CVC coating was progressively eroded by blood-flow, and that the antibacterial function was lost after 48 hours.

Research in 2018 into the treatment of central nervous system infections caused by free-living amoebae such as Naegleria fowleri and Acanthamoeba castellanii, tested the effectiveness of existing drugs as well as the effectiveness of the same drugs when they were conjugated with silver nanoparticles. In vitro tests demonstrated more potent amoebicidal effects for the drugs when conjugated with silver nanoparticles as compared to the same drugs when used alone. They also found that conjugating the drugs with silver nanoparticles enhanced their anti-acanthamoebic activity.{{cite journal | vauthors = Anwar A, Rajendran K, Siddiqui R, Raza Shah M, Khan NA | title = Clinically Approved Drugs against CNS Diseases as Potential Therapeutic Agents To Target Brain-Eating Amoebae | journal = ACS Chemical Neuroscience | volume = 10 | issue = 1 | pages = 658–666 | date = January 2019 | pmid = 30346711 | doi = 10.1021/acschemneuro.8b00484 | s2cid = 53037286 }}

Silver-halide imaging plates used with X-ray imaging were the standard before digital techniques arrived; these function essentially the same as other silver-halide photographic films, although for x-ray use the developing process is very simple and takes only a few minutes. Silver x-ray film remains popular for its accuracy, and cost effectiveness, particularly in developing countries, where digital X-ray technology is usually not available.{{cite journal | vauthors = Zennaro F, Oliveira Gomes JA, Casalino A, Lonardi M, Starc M, Paoletti P, Gobbo D, Giusto C, Not T, Lazzerini M | display-authors = 6 | title = Digital radiology to improve the quality of care in countries with limited resources: a feasibility study from Angola | journal = PLOS ONE | volume = 8 | issue = 9 | pages = e73939 | year = 2013 | pmid = 24086301 | pmc = 3783475 | doi = 10.1371/journal.pone.0073939 | bibcode = 2013PLoSO...873939Z | doi-access = free }}

Silver compounds have been used in external preparations as antiseptics, including both silver nitrate and silver proteinate. Before the development of antibiotics, Credé's prophylaxis used a 2% solution of silver nitrate to prevent neonatal conjunctivitis, which used to account for half of all cases of blindness in Europe. {{Citation |last=Schmidt |first=Axel |title=Gonorrheal ophthalmia neonatorum: Historic impact of Credé's eye prophylaxis |date=2007 |url=https://doi.org/10.1007/978-3-7643-8099-1_4 |work=Pediatric Infectious Diseases Revisited |pages=95–115 |editor-last=Schroten |editor-first=Horst |access-date=2023-11-04 |series=Birkhäuser Advances in Infectious Diseases |place=Basel |publisher=Birkhäuser |language=en |doi=10.1007/978-3-7643-8099-1_4 |isbn=978-3-7643-8099-1 |editor2-last=Wirth |editor2-first=Stefan}}{{cite journal |last1=Schaller |first1=U. C. |last2=Klauss |first2=V. |title=Is Credé's prophylaxis for ophthalmia neonatorum still valid? |journal=Bulletin of the World Health Organization |date=2001 |volume=79 |issue=3 |pages=262–263 |pmid=11285676 |pmc=2566367 |hdl=10665/74722 |hdl-access=free }} The original procedure called for a 2% silver nitrate solution administered immediately after birth, as Credé erroneously believed that a 1% solution was ineffective due to a previous study by Hecker; however, this was eventually corrected and reduced back down to a 1% solution to reduce chemical irritation to the newborn's eyes.

Silver nitrate is also sometimes used in dermatology in solid stick form as a caustic ("lunar caustic") to treat certain skin conditions, such as corns and warts.{{cite web|title=Colloidal Silver|url=https://nccih.nih.gov/health/silver|publisher=National Center for Complementary and Integrative Health|access-date=9 October 2016|date=July 2009}}

Silver nitrate is also used in certain laboratory procedures to stain cells. As it turns them permanently a dark-purple/black color, in doing so increasing individual cells' visibility under a microscope and allowing for differentiation between cells, or identification of irregularities.

Silver is also used in bone prostheses and cardiac devices. In reconstructive hip and knee surgery, silver-coated titanium prostheses are indicated in cases of recalcitrant prosthetic joint infections.{{cite journal |vauthors=Kontakis MG, Diez-Escudero A, Hariri H, Andersson B, Järhult JD, Hailer NP | title = Antimicrobial and osteoconductive properties of two different types of titanium silver coating | journal = European Cells & Materials | volume = 41 | pages = 694–706 | date = June 2021 | pmid = 34121171 | doi = 10.22203/eCM.v041a45 | s2cid = 235423883 | doi-access = free }} Silver diammine fluoride appears to be an effective intervention to reduce dental caries (tooth decay).{{cite journal | vauthors = Rosenblatt A, Stamford TC, Niederman R | title = Silver diamine fluoride: a caries 'silver-fluoride bullet' | journal = Journal of Dental Research | volume = 88 | issue = 2 | pages = 116–125 | date = February 2009 | pmid = 19278981 | doi = 10.1177/0022034508329406 | s2cid = 30730306 }}{{cite journal | vauthors = Deery C | title = Silver lining for caries cloud? | journal = Evidence-Based Dentistry | volume = 10 | issue = 3 | pages = 68 | year = 2009 | pmid = 19820733 | doi = 10.1038/sj.ebd.6400661 | doi-access = free }} Silver is also a component in dental amalgam.

Silver acetate has been used as a potential aid to help stop smoking; a review of the literature in 2012, however, found no effect of silver acetate on smoking cessation at a six-month endpoint and if there is an effect it would be small.{{cite journal | vauthors = Lancaster T, Stead LF | title = Silver acetate for smoking cessation | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD000191 | date = September 2012 | volume = 2012 | pmid = 22972041 | pmc = 7043308 | doi = 10.1002/14651858.CD000191.pub2 }} Silver has also been used in cosmetics, intended to enhance antimicrobial effects and the preservation of ingredients.{{cite journal | vauthors = Kokura S, Handa O, Takagi T, Ishikawa T, Naito Y, Yoshikawa T | title = Silver nanoparticles as a safe preservative for use in cosmetics | journal = Nanomedicine | volume = 6 | issue = 4 | pages = 570–574 | date = August 2010 | pmid = 20060498 | doi = 10.1016/j.nano.2009.12.002 }}

{{main|Argyria}}

Though toxicity of silver is low, the human body has no biological use for silver and when inhaled, ingested, injected, or applied topically, silver can accumulate irreversibly in the body, particularly in the skin, and chronic use combined with exposure to sunlight can result in a disfiguring condition known as argyria in which the skin becomes blue or blue-gray. Localized argyria can occur as a result of topical use of silver-containing creams and solutions, while the ingestion, inhalation, or injection can result in generalized argyria.{{cite journal | vauthors = Brandt D, Park B, Hoang M, Jacobe HT | title = Argyria secondary to ingestion of homemade silver solution | journal = Journal of the American Academy of Dermatology | volume = 53 | issue = 2 Suppl 1 | pages = S105-7 | date = August 2005 | pmid = 16021155 | doi = 10.1016/j.jaad.2004.09.026 }}{{cite journal | vauthors = Okan D, Woo K, Sibbald RG | title = So what if you are blue? Oral colloidal silver and argyria are out: safe dressings are in | journal = Advances in Skin & Wound Care | volume = 20 | issue = 6 | pages = 326–30 | date = June 2007 | pmid = 17538258 | doi = 10.1097/01.ASW.0000276415.91750.0f | s2cid = 31383370 }} Preliminary reports of treatment with laser therapy have been reported. These laser treatments are painful and general anesthesia is required.{{cite journal | vauthors = Rhee DY, Chang SE, Lee MW, Choi JH, Moon KC, Koh JK | title = Treatment of argyria after colloidal silver ingestion using Q-switched 1,064-nm Nd:YAG laser | journal = Dermatologic Surgery | volume = 34 | issue = 10 | pages = 1427–30 | date = October 2008 | pmid = 18657163 | doi = 10.1111/j.1524-4725.2008.34302.x }}{{cite journal | vauthors = Jacobs R | title = Argyria: my life story | journal = Clinics in Dermatology | volume = 24 | issue = 1 | pages = 66–9; discussion 69 | year = 2006 | pmid = 16427508 | doi = 10.1016/j.clindermatol.2005.09.001 }} A similar laser treatment has been used to clear silver particles from the eye, a condition related to argyria called argyrosis.{{cite journal | vauthors = Geyer O, Rothkoff L, Lazar M | title = Clearing of corneal argyrosis by YAG laser | journal = The British Journal of Ophthalmology | volume = 73 | issue = 12 | pages = 1009–10 | date = December 1989 | pmid = 2611183 | pmc = 1041957 | doi = 10.1136/bjo.73.12.1009 }} The Agency for Toxic Substances and Disease Registry (ATSDR) describes argyria as a "cosmetic problem".{{cite web |url=https://wwwn.cdc.gov/TSP/ToxFAQs/ToxFAQsLanding.aspx?id=538&tid=97 |publisher=Agency for Toxic Substances and Disease Registry |title=ToxFAQs for Silver |access-date=October 9, 2016 |format=Page last updated: March 26, 2014 }}

One incident of argyria came to the public's attention in 2008, when a man named Paul Karason, whose skin turned blue from using colloidal silver for over 10 years to treat dermatitis, appeared on NBC's Today show. Karason died in 2013 at the age of 62 after a heart attack.Moran, Lee. (2013-09-25) [http://www.nydailynews.com/news/national/man-turned-blue-silver-dies-article-1.1466905 Man who turned blue after taking silver for skin condition dies]. Nydailynews.com. Retrieved on 2016-11-26. Another example is Montana politician Stan Jones whose purposeful consumption of colloidal silver was a self-prescribed measure he undertook in response to his fears that the Y2K problem would make antibiotics unavailable, an event that did not occur.{{cite web|url=https://www.npr.org/templates/story/story.php?storyId=128588187|title=Fun And Intrigue With The Periodic Table|author=All Things Considered|publisher=National Public Radio|date=July 17, 2010|access-date=August 10, 2021}}

Colloidal silver may interact with some prescription medications, reducing the absorption of some antibiotics and thyroxine, among others.{{Cite web | title = Colloidal Silver Products |date=July 2009 | url = http://nccih.nih.gov/health/silver | archive-url = https://web.archive.org/web/20120203081051/http://wellnessproposals.com/health-care/complimentary-and-alternative-medicine/colloidal-silver-products.pdf | archive-date = 3 February 2012 |work=Backgrounder |publisher=U.S. Department of Health and Human Services |via=Wellness Proposals}}

Some people are allergic to silver, and the use of treatments and medical devices containing silver is contraindicated for such people. Although medical devices containing silver are widely used in hospitals, no thorough testing and standardization of these products has yet been undertaken.

Electrolytically dissolved silver has been used as a water disinfecting agent, for example, the drinking water supplies of the Russian Mir orbital station and the International Space Station.{{cite book | title = Spacecraft Water Exposure Guidelines for Selected Contaminants |volume=1 | year = 2004 | url = http://books.nap.edu/openbook.php?record_id=10942&page=324 | page = 324 |isbn=978-0-309-09166-4 |publisher=National Academies Press| doi = 10.17226/10942 }} Many modern hospitals filter hot water through copper-silver filters to defeat MRSA and legionella infections.{{cite book | vauthors = Lansdown AB |title=Silver in Healthcare: Its Antimicrobial Efficacy and Safety in Use|url=https://books.google.com/books?id=QxtLm7MgQhYC|access-date=20 January 2013|date=27 May 2010|publisher=Royal Society of Chemistry|isbn=978-1-84973-006-8}}{{rp|29}} The World Health Organization (WHO) includes silver in a colloidal state produced by electrolysis of silver electrodes in water, and colloidal silver in water filters as two of a number of water disinfection methods specified to provide safe drinking water in developing countries.{{cite web | publisher = World Health Organization | url = http://whqlibdoc.who.int/paho/2003/a85637.pdf | archive-url = https://web.archive.org/web/20060710063629/http://whqlibdoc.who.int/paho/2003/a85637.pdf | url-status = dead | archive-date = July 10, 2006 | title = Water Disinfection | vauthors = Solsona F, Mendez JP | year = 2003}} Along these lines, a ceramic filtration system coated with silver particles has been created by Ron Rivera of Potters for Peace and used in developing countries for water disinfection (in this application the silver inhibits microbial growth on the filter substrate, to prevent clogging, and does not directly disinfect the filtered water).{{cite news | vauthors = Richmond C | title=Ron Rivera: Potter who developed a water filter that saved lives in the third world | date=2008-10-16 | url =https://www.theguardian.com/science/2008/oct/16/1 | work =The Guardian | access-date = 2009-05-16 }}{{cite news | work = New York Times | title = Solution in a Pot | url = https://www.nytimes.com/2008/12/28/magazine/28rivera-t.html | vauthors = Corbett S | date = December 24, 2008 | access-date = May 15, 2009}}{{cite book |title=Mobilizing Science-Based Enterprises for Energy, Water, and Medicines in Nigeria |url=https://archive.org/details/mobilizingscienc00acad|url-access=limited|publisher=National Academies Press |location=Washington, D.C. |year=2007 |page=[https://archive.org/details/mobilizingscienc00acad/page/n53 39] |isbn=978-0-309-11118-8}}

{{Infobox:Alternative therapy

|name = Colloidal silver

|image = Plata Coloidal Super Tyndall Effect.jpeg

|caption = A bottle of colloidal silver

|NCCIH =

|school =

|risks = Argyria, decreased drug absorption,

|legality =Not to be sold for consumption or disinfection in Sweden.{{cite web|title=Vad gäller om jag vill sälja kolloidalt silver som biocidprodukt?|url=http://www.kemi.se/en/fraga/vad-galler-om-jag-vill-salja-kolloidalt-silver-som-biocidprodukt/|publisher=Kemi (Swedish Chemicals Agency)|archive-url=https://web.archive.org/web/20161010001325/http://www.kemi.se/en/fraga/vad-galler-om-jag-vill-salja-kolloidalt-silver-som-biocidprodukt/|access-date=9 October 2016|archive-date=2016-10-10}} Not to treat or prevent cancer (UK, Sweden, etc.) Illegal to be marketed/advertised as a dietary supplement or medicine in the U.S. |MeshID =

|benefits = Antibacterial

}}

Colloidal silver (a colloid consisting of silver particles suspended in liquid) and formulations containing silver salts were used by physicians in the early 20th century, but their use was largely discontinued in the 1940s following the development of modern antibiotics.{{cite journal | vauthors = Fung MC, Bowen DL | title = Silver products for medical indications: risk-benefit assessment | journal = Journal of Toxicology. Clinical Toxicology | volume = 34 | issue = 1 | pages = 119–126 | year = 1996 | pmid = 8632503 | doi = 10.3109/15563659609020246 }} Since about 1990, there has been a resurgence of the promotion of colloidal silver as a dietary supplement, marketed with claims of it being an essential mineral supplement, or that it can prevent or treat numerous diseases, such as cancer, diabetes, arthritis, HIV/AIDS, herpes, and tuberculosis.{{cite journal | vauthors = Wadhera A, Fung M | title = Systemic argyria associated with ingestion of colloidal silver | journal = Dermatology Online Journal | volume = 11 | issue = 1 | pages = 12 | date = March 2005 | doi = 10.5070/D30832G6D3 | pmid = 15748553 | url = http://dermatology.cdlib.org/111/case_reports/argyria/wadhera.html }}{{cite journal | vauthors = Fung MC, Weintraub M, Bowen DL | title = Colloidal silver proteins marketed as health supplements | journal = JAMA | volume = 274 | issue = 15 | pages = 1196–97 | date = October 1995 | pmid = 7563503 | doi = 10.1001/jama.1995.03530150020017 }} No medical evidence supports the effectiveness of colloidal silver for any of these claimed indications.{{cite journal | vauthors = | title = Over-the-counter drug products containing colloidal silver ingredients or silver salts. Department of Health and Human Services (HHS), Public Health Service (PHS), Food and Drug Administration (FDA). Final rule | journal = Federal Register | volume = 64 | issue = 158 | pages = 44653–44658 | date = August 1999 | pmid = 10558603 | url = https://www.govinfo.gov/content/pkg/FR-1999-08-17/pdf/99-21253.pdf }}{{cite journal | vauthors = Newman M, Kolecki P | title = Argyria in the ED | journal = The American Journal of Emergency Medicine | volume = 19 | issue = 6 | pages = 525–26 | date = October 2001 | pmid = 11593479 | doi = 10.1053/ajem.2001.25773 }} Silver is not an essential mineral in humans; there is no dietary requirement for silver, and hence, no such thing as a silver "deficiency". There is no evidence that colloidal silver treats or prevents any medical condition, and it can cause serious and potentially irreversible side effects, such as argyria.

In August 1999, the U.S. FDA banned colloidal silver sellers from claiming any therapeutic or preventive value for the product, although silver-containing products continue to be promoted as dietary supplements in the U.S. under the looser regulatory standards applied to supplements. The FDA has issued numerous warning letters to Internet sites that have continued to promote colloidal silver as an antibiotic or for other medical purposes.{{cite web |url= https://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm127976.htm|title= Colloidal Silver Not Approved|access-date=2008-09-22 |publisher=U.S. Food and Drug Administration|date=2007-02-12}}{{cite web|url=https://www.fda.gov/cder/warn/cyber/2001/Cyber097.pdf|title=FDA Warning Letter|access-date=2008-09-22|publisher=U.S. Food and Drug Administration|date=2001-03-13}}{{cite web |url=https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm253264.htm|title=FDA Warning Letter|access-date=2013-04-11|publisher=U.S. Food and Drug Administration|year=2011}} Despite the efforts of the FDA, silver products remain widely available on the market today. A review of websites promoting nasal sprays containing colloidal silver suggested that information about silver-containing nasal sprays on the Internet is misleading and inaccurate.{{cite journal | vauthors = Gaslin MT, Rubin C, Pribitkin EA | title = Silver nasal sprays: misleading Internet marketing | journal = Ear, Nose, & Throat Journal | volume = 87 | issue = 4 | pages = 217–220 | date = April 2008 | pmid = 18478796 | doi = 10.1177/014556130808700414 | doi-access = free }} Colloidal silver is also sold in some topical cosmetics, as well as some toothpastes, which are regulated by the FDA as cosmetics (other than drug ingredients making medical claims).[https://www.fda.gov/cosmetics/cosmetics-laws-regulations/it-cosmetic-drug-or-both-or-it-soap "Is It a Cosmetic, a Drug, or Both? (Or Is It Soap?)"] Food and Drug Administration.

In 2002, the Australian Therapeutic Goods Administration (TGA) found there were no legitimate medical uses for colloidal silver and no evidence to support its marketing claims.{{cite web|url=http://www.tga.gov.au/industry/cm-colloidal-silver.htm|title=Regulation of colloidal silver and related products|publisher=Australian Therapeutic Goods Administration|access-date=2008-09-22|date=2005-11-09|archive-date=2014-09-30|archive-url=https://web.archive.org/web/20140930141203/http://www.tga.gov.au/industry/cm-colloidal-silver.htm|url-status=dead}} The U.S. National Center for Complementary and Integrative Health (NCCIH) warns that marketing claims about colloidal silver are scientifically unsupported, that the silver content of marketed supplements varies widely, and that colloidal silver products can have serious side effects such as argyria.

In 2009, the USFDA issued a consumer advisory warning about the potential adverse effects of colloidal silver, and said that "there are no legally marketed prescription or over-the-counter (OTC) drugs containing silver that are taken by mouth".[https://www.fda.gov/Food/RecallsOutbreaksEmergencies/SafetyAlertsAdvisories/ucm184087.htm "Dietary Supplements Containing Silver May Cause Permanent Discoloration of Skin and Mucous Membranes (Argyria)"]. FDA Consumer Advisory (October 6, 2009). Quackwatch states that colloidal silver dietary supplements have not been found safe or effective for the treatment of any condition.{{cite web |url = http://www.quackwatch.org/01QuackeryRelatedTopics/lyme.html |title = Lyme Disease: Questionable Diagnosis and Treatment |vauthors = McSweegan E |publisher = Quackwatch |access-date = October 9, 2016 |archive-url = https://web.archive.org/web/20140209034930/http://quackwatch.org/01QuackeryRelatedTopics/lyme.html |archive-date = February 9, 2014 |url-status = dead }} Consumer Reports lists colloidal silver as a "supplement to avoid", describing it as "likely unsafe".{{cite web | title = Twelve supplements you should avoid | date = September 2010 | access-date = January 31, 2013 | work = Consumer Reports | url = http://www.consumerreports.org/cro/magazine-archive/2010/september/health/dangerous-supplements/supplements-to-avoid/index.htm}} The Los Angeles Times stated that "colloidal silver as a cure-all is a fraud with a long history, with quacks claiming it could cure cancer, AIDS, tuberculosis, diabetes, and numerous other diseases".{{cite news | work = The Los Angeles Times | title = Scam 'cures' for swine flu face crackdown | date = May 2, 2009 | access-date = May 23, 2022 | url = https://www.latimes.com/archives/la-xpm-2009-may-02-fi-swine-flu-scams2-story.html | vauthors = Colker D | url-status = live | archive-url = https://web.archive.org/web/20121111135157/http://articles.latimes.com/2009/may/02/business/fi-swine-flu-scams2 | archive-date = November 11, 2012 }}

It may be illegal to market as a preventive or as a treatment for cancer, and in some jurisdictions to sell colloidal silver for consumption.{{cite web|title=Kolloidalt silver|url=http://www.livsmedelsverket.se/livsmedel-och-innehall/oonskade-amnen/kolloidalt-silver|publisher=Livsmedelsverket (Swedish Food Agency)|access-date=9 October 2016}} In 2015 an English man was prosecuted and found guilty under the Cancer Act 1939 for selling colloidal silver with claims it could treat cancer.{{cite web | url=http://www.chelmsfordweeklynews.co.uk/news/maldon/11473350.Man_is_fined_after_selling__cancer_cure__which_he_made_at_home/ | title=Man is fined after selling 'cancer cure' which he made at home | publisher=Chelmsford Weekly News | date=15 September 2014 | access-date=16 November 2014}}

{{further|COVID-19 misinformation}}

The US Food and Drug Administration has issued warning letters to firms including colloidal silver marketers for selling products with false and misleading claims to prevent, treat, mitigate, diagnose or cure coronavirus disease 2019 (COVID-19).{{cite web |title=Fraudulent Coronavirus Disease 2019 (COVID-19) Products |url=https://www.fda.gov/consumers/health-fraud-scams/fraudulent-coronavirus-disease-2019-covid-19-products |publisher= US Food and Drug Administration| access-date=8 April 2020 |date=7 April 2020}}

In 2020, televangelist felon Jim Bakker was sued by the Missouri Attorney General (AG) for marketing colloidal silver products and making false claims about their effectiveness against COVID-19. The Attorney General of New York sent a cease and desist order to Bakker and others about peddling the unproven products that were compared to selling "snake oil", and the Food and Drug Administration also warned Bakker about his actions.{{cite news| url= https://www.npr.org/2020/03/11/814550474/missouri-sues-televangelist-jim-bakker-for-selling-fake-coronavirus-cure |title= Missouri Sues Televangelist Jim Bakker For Selling Fake Coronavirus Cure| date= 11 March 2020| website= NPR| first= Matthew S. | last= Schwartz| access-date= 13 May 2021}}

Controversial web show host, podcaster and conspiracy theorist Alex Jones was also warned by the New York Attorney General's office to stop marketing his colloidal silver infused products (toothpaste, mouthwash, dietary supplements, etc.) because he made unproven claims of its ability to fend off COVID-19.{{cite news| url= https://www.usatoday.com/story/news/nation/2020/03/13/infowars-alex-jones-stop-selling-fake-coronavirus-cures/5044309002/ |work= USA Today| title= Conspiracy theorist Alex Jones ordered to stop peddling phony coronavirus cures by New York AG| date= 13 March 2020| first= Joshua| last= Bote| publisher= | access-date= 13 May 2021}}

Hippocrates in his writings discussed the use of silver in wound care.{{cite journal | vauthors = Dai T, Huang YY, Sharma SK, Hashmi JT, Kurup DB, Hamblin MR | title = Topical antimicrobials for burn wound infections | journal = Recent Patents on Anti-Infective Drug Discovery | volume = 5 | issue = 2 | pages = 124–51 | date = June 2010 | pmid = 20429870 | pmc = 2935806 | doi = 10.2174/157489110791233522 }} At the beginning of the twentieth century surgeons routinely used silver sutures to reduce the risk of infection.{{cite journal | vauthors = Alexander JW | title = History of the medical use of silver | journal = Surgical Infections | volume = 10 | issue = 3 | pages = 289–92 | date = June 2009 | pmid = 19566416 | doi = 10.1089/sur.2008.9941 }} In the early 20th century, physicians used silver-containing eyedrops to treat ophthalmic problems,{{cite journal | vauthors = Roe AL | title = Collosol Argentum and ITS Ophthalmic Uses | journal = British Medical Journal | volume = 1 | issue = 2820 | pages = 104 | date = January 1915 | pmid = 20767446 | pmc = 2301624 | doi = 10.1136/bmj.1.2820.104 }} for various infections,{{cite journal |doi=10.1016/S0140-6736(01)66545-0 |title=Electric Metallic Colloids and Their Therapeutical Applications |journal=The Lancet |volume=179 |issue=4614 |pages=322–323 |year=1912 | vauthors = MacLeod CE }}{{cite book| vauthors = Searle AB |title=The Use of Colloids in Health and Disease|publisher=London Constable & Co. |location=Gerstein-University of Toronto : Toronto Collection|year=1920|chapter=Chapter IX: Colloidal Remedies and Their Uses|chapter-url=https://archive.org/stream/useofcolloidsinh00searuoft#page/83/mode/1up }} and sometimes internally for diseases such as tropical sprue,{{cite journal | vauthors = Cantlie J |title= Some recent observations on sprue |journal=BMJ |volume=2 |issue=2759 |pages=1296–7 |year=1913 |doi=10.1136/bmj.2.2759.1282 | pmc = 2345624 }} epilepsy, gonorrhea, and the common cold.{{cite web | publisher = Memorial Sloan-Kettering Cancer Center | url = http://www.mskcc.org/cancer-care/herb/colloidal-silver |title = Colloidal silver| date = May 16, 2011 | access-date = January 2, 2013}} During World War I, soldiers used silver leaf to treat infected wounds.{{cite journal | vauthors = Borsuk DE, Gallant M, Richard D, Williams HB | title = Silver-coated nylon dressings for pediatric burn victims | journal = The Canadian Journal of Plastic Surgery | volume = 15 | issue = 1 | pages = 29–31 | year = 2007 | pmid = 19554127 | pmc = 2686041 | doi = 10.1177/229255030701500111 }}

In the 1840s, founder of gynecology J. Marion Sims employed silver wire, which he had a jeweler fashion, as a suture in gynecological surgery. This produced very favorable results when compared with its predecessors, silk and catgut.

Prior to the introduction of modern antibiotics, colloidal silver was used as a germicide and disinfectant.{{cite book| vauthors = Searle AB |title=The Use of Colloids in Health and Disease|publisher=London Constable & Co.|location=Gerstein – University of Toronto : Toronto Collection|year=1920|chapter=Chapter VIII: Germicides and Disinfectants|chapter-url=https://archive.org/stream/useofcolloidsinh00searuoft#page/70/mode/2up }} With the development of modern antibiotics in the 1940s, the use of silver as an antimicrobial agent diminished, although it retains some use in medicinal compounds today. Silver sulfadiazine (SSD) is a compound containing silver and the antibiotic sodium sulfadiazine, which was developed in 1968.{{cite journal | vauthors = Chopra I | title = The increasing use of silver-based products as antimicrobial agents: a useful development or a cause for concern? | journal = The Journal of Antimicrobial Chemotherapy | volume = 59 | issue = 4 | pages = 587–90 | date = April 2007 | pmid = 17307768 | doi = 10.1093/jac/dkm006 | doi-access = free }}

The National Health Services in the UK spent about £25 million on silver-containing dressings in 2006. Silver-containing dressings represent about 14% of the total dressings used and about 25% of the overall wound dressing costs.{{cite journal | vauthors = | title = Silver dressings--do they work? | journal = Drug and Therapeutics Bulletin | volume = 48 | issue = 4 | pages = 38–42 | date = April 2010 | pmid = 20392779 | doi = 10.1136/dtb.2010.02.0014 | s2cid = 206924334 }}

Concerns have been expressed about the potential environmental cost of manufactured silver nanomaterials in consumer applications being released into the environment, for example that they may pose a threat to benign soil organisms.{{cite journal | vauthors = Tolaymat TM, El Badawy AM, Genaidy A, Scheckel KG, Luxton TP, Suidan M | title = An evidence-based environmental perspective of manufactured silver nanoparticle in syntheses and applications: a systematic review and critical appraisal of peer-reviewed scientific papers | journal = The Science of the Total Environment | volume = 408 | issue = 5 | pages = 999–1006 | date = February 2010 | pmid = 19945151 | doi = 10.1016/j.scitotenv.2009.11.003 | bibcode = 2010ScTEn.408..999T | url = https://zenodo.org/record/1000724 }}

• List of ineffective cancer treatments
• Colloidal gold
• Antibiotic properties of nanoparticles

{{reflist}}

• {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/silver | publisher = U.S. National Library of Medicine| work = Drug Information Portal | title = Silver }}
• {{cite web| url = http://www.mskcc.org/cancer-care/herb/colloidal-silver | title = Integrative Medicine: Colloidal Silver | date = 10 February 2023 | publisher = Memorial Sloan-Kettering Cancer Center}}

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