Silver nasal sprays: misleading Internet marketing.

Abstract

Long-term use of silver-containing products is associated with a permanent bluish-gray discoloration of the skin known as argyria, but they remain widely available despite several measures by the FDA to regulate them. Several recent case reports have described the occurrence of argyria as a result of using these "natural" products. We used the five most common Internet search engines to find Web sites providing information on silver-containing nasal sprays. Of 49 Web sites analyzed, only 2 (4%) mentioned argyria as a possible complication, although 30 (61%) did caution against long-term use. Eight sites (16%) made specific claims about the health benefits of the product. All 49 sites (100%) provided direct or indirect links to buy silver-containing nasal sprays. We conclude that information about silver-containing nasal sprays on the Internet is misleading and inaccurate. Therefore, otolaryngologists should be aware of the misinformation their patients may be receiving about these products.

Introduction

Argyria is a permanent and disfiguring bluish-gray discoloration of the skin associated with long-term use of products containing silver (see photos at http:// rosemaryjacobs.com/argyria_photos_intro.html). Silver-containing products are readily available to consumers despite the health risks associated with exposure to soluble silver compounds. Otolaryngologists should be aware of the misinformation available to consumers about these potentially dangerous products.

Silver compounds have a long history of medicinal use. The ancient physician Avicenna (980-1037 AD) is said to have been the first to describe their use as a blood purifier, a treatment for halitosis, and for heart conditions. Interestingly, Avicenna also noted that some patients using his formulations developed a bluish discoloration of the eyes, likely an early description of argyria. (1) In 1859, Frommann reported a case of argyria caused by the use of silver nitrate as an antimicrobial. (2)

In 1902, Albert C. Barnes formed the firm of Barnes & Hille, selling the product Argyrol, an antiseptic silver compound? Barnes amassed a fortune from sales of the product, (3) but he and the public did not realize the consequences of long-term use of silver. Cases of generalized argyria were more prevalent in the first half of the 20th century because of the use of silver-containing compounds as medicinals and increased occupational exposure in the silver industry. In the second half of the 20th century, widespread use of silver-containing compounds decreased as knowledge of their side effects increased.

In 1994, Congress passed the Dietary Supplement Health and Education Act (DSHEA), restricting the Food and Drug Administration's (FDA's) control over dietary supplements. Unfortunately, colloidal silver products had previously qualified as dietary supplements in the FDA's original rulings and so became available for legal sale in the United States. Increased marketing on the Internet caused the sales of silver-containing medicinal products to grow rapidly. Realizing the problem, in 1999 the FDA amended the DSHEA specifically for colloidal silver products, stating "... All over-the-counter drug products containing colloidal silver ingredients or silver salts are not generally recognized as safe and effective and are misbranded.'' (4) Subsequently, the FDA and the Federal Trade Commission sent warning letters to the operators of many Web sites that market colloidal silver with drug-like claims (i.e., that their product diagnoses, treats, cures, or prevents disease). Despite these efforts, silver products remain widely available on the market today.

Several recent case reports of argyria from the use of silver-containing products have been described. Formulations associated with recent cases of argyria include topical nasal sprays for allergies, (5-7) silver-containing nutritional supplements, (8,9) homemade remedies containing silver, (10) silver therapies for diabetes, (11) and a colloidal silver preparation to treat arthritis. (12)

Silver formulations

Silver-containing products come in several different formulations. Colloidal silver is a suspension of submicroscopic silver particles in a liquid base. It is the most common formulation in silver-containing nasal sprays and is the most common form marketed on the Internet. Other common formulations include the topical antibiotic silver sulfadiazine and the topical cauterizing agent silver nitrate.

Silver-containing products are believed to produce their antimicrobial effect by reacting with and denaturing bacterial proteins, affecting the bacterial cell wall and cell membrane. (13) However, in 2004, van Hasselt et al conducted in vitro tests in which colloidal silver concentrations as high as 413 parts per million (ppm) showed no antimicrobial activity against a variety of bacteria. (14) These researchers question the validity of using silver-containing products as antimicrobials.

Silver and argyria

The adverse effects of silver-containing products depend on the cumulative dose, route and duration of exposure, and the general health of the exposed individual. Argyria can result in either generalized or localized discoloration of the skin, depending on the route of exposure. Generalized argyria requires a route of administration that allows silver to enter the bloodstream, for example via ingestion of silver products, use of silver nasal sprays, or intravenous administration. Localized argyria is caused by local exposure to silver, for example by silver jewelry or silver sulfadiazine cream.

The precise pathway by which silver products reach the skin is not completely understood. Serum analysis of patients up to 3 years after exposure to orally administered silver show persistently elevated levels of silver, with low urinary excretion. (9) Therefore, systemic exposure to silver can result in long-lasting and continuously elevated blood levels. Rosemary Jacobs, a woman who developed argyria as a young girl in the 1950s after using silver-containing nose drops recommended by her physician, has suffered with the condition throughout her life. She has become an advocate for people with argyria and for the regulation of the silver medications industry. Her story can be found at http://rosemaryjacobs.com/.

In silver-exposed skin, light microscopy reveals granules in the dermis, most prominently around the basement membranes of eccrine sweat glands, or in dermal elastic fibers. (15) These particles are composed predominantly either of silver sulfide or silver selenide; over time, most of the silver sulfide is replaced with silver selenide. (16) Silver can also be found intracellularly in endothelial cells of small blood vessels, mast cells, fibroblasts, and in the perineurium of peripheral nerves. However, silver is not found in the epidermis, and therefore it is unlikely that silver is excreted through the skin. (15)

General exposure to silver in the environment is relatively low. The Environmental Protection Agency's upper limit for silver levels in drinking water is 50 parts per billion. However, this is 1,000 times less concentrated than the silver found in many silver-containing medicinals, which is approximately 50 ppm.

The amount of silver needed to cause argyria is not known, but studies using silver to treat syphilis in the preantibiotic era showed a link between argyria and a cumulative dose of intravenous silver arsphenamine that exceeded 4 g intravenously. (17) The Occupational Safety and Health Administration has set the permissible exposure limit for all forms of silver at 0.01 mg/[m.sup.3]. (18)

Drake and Hazelwood, in their review of the exposure-related health effects of silver and silver compounds, note, "Besides argyria and argyrosis, exposure to soluble silver compounds may produce other toxic effects, including liver and kidney damage, irritation of the eyes, skin, respiratory, and intestinal tract, and changes in blood cells." (18) They also state, "Silver in any form is not thought to be toxic to the immune, cardiovascular, nervous, or reproductive systems and is not considered carcinogenic.'' (18)

Marketing issues: What do the Web sites claim?

Colloidal silver products are often marketed with unproven health-related claims, such as products benefiting the immune system; killing disease-causing agents such as bacteria, viruses, and fungi; being an alternative to prescription antibiotics; or treating diseases such as cancer and human immunodeficiency virus.

In a recent study of Internet marketing of the most common herbal remedies, Morris and Avorn discovered that, despite FDA regulations on the health claims of herbal products, 55% of herbal medication Web sites made claims to treat, prevent, diagnose, or cure specific diseases. (19)

In addition to making specific health claims and marketing their products, Web sites are unlikely to reveal potential side effects of their products. A study of information available on the Internet regarding ephedra usage, for example, revealed that 41% of Web sites failed to disclose potential adverse effects. (20) Although silver-containing products are regulated more strictly than other types of herbal products, health and other claims about silver products are easily found with the most common search engines.

[FIGURE OMITTED]

Using the five most common search engines (Google, Yahoo, Ask.com (formerly AskJeeves.com), MSN.com, and America Online), we searched the Internet for the term silver nasal spray so that we could analyze the content of sites that were marketing this product. To be included in our study, sites had to contain all of the following information about silver containing nasal sprays: health information, marketing of products, side effects, historical information, and information on formulations. Sites that did not contain any of the above information or that were not written in English were excluded.

The top 20 sites from each search engine meeting the inclusion criteria were analyzed. Many sites were found by more than one search engine, but each site was analyzed only once. Information regarding health claims, contraindications to use, adverse effects, dosing, formulation, disclaimers, nutrition information, information about structure, and the cost of the product was extracted from the sites. All data were collected in a standardized spreadsheet.

A total of 49 web sites were analyzed. Their content is summarized in the figure. Eight (16%) of the sites made specific claims about the health benefits of the product. Examples of those claims are presented in the table. We found only 1 site (2%) that was dedicated to the negative health consequences of using silver-containing products but, ironically, this same site contained a direct link to a site selling silver-containing nasal sprays.

Of all the sites included in our study, only 2 (4%) mentioned argyria as a possible complication of colloidal silver, although 30 (61%) did warn against long-term use. The most common warning, found in >90% of the sites that cautioned against long-term use, was to limit use to a 10-day period and not to use the product continuously. None of the sites reviewed mentioned a relationship between a cumulative dose and side effects.

Formulations of products ranged from 10 to 132 ppm. Information about quality control in the manufacturing of the products was sparse. There did not appear to be a relationship between the dose of the product and the indication for which it was recommended. Recommended dosage varied from 1 to 6 sprays per nostril per day, or "use as needed."

Disclaimers about the lack of FDA approval for these products were mentioned on 26 (53%) sites. All 49 sites (100%) provided direct or indirect links for purchasing silver-containing nasal sprays.

Discussion

Many of the recent case reports of argyria mention that the patients directly purchased the product over the Internet. Even though a direct link to the Internet was not found in all cases, we must remember that many consumers use the Internet to research health information and to make decisions about treatment, particularly for nontraditional medical therapies.

The fact that all 49 web sites we found have direct links for buying silver-containing nasal products is evidence that these products are widely available. This ease of buying products online is compounded by the lack of information exchange between patients and healthcare providers when products are purchased in this way. Consumers have little or no means of assessing the validity of the claims made on Web sites, so they are potentially using products about which they know very little. With frequent reassurances of safety conveyed on these sites, consumers are unlikely to realize the potential dangers of "natural" medicinals.

The misinformation carried on many Web pages directly violates FDA rules regarding the marketing of products labeled as nutritional supplements. These rules prohibit claims to diagnose, mitigate, treat, cure, or prevent disease. Although providing basic information about the structure and function of a compound is acceptable, as well as providing its nutritional content and generalized claims of well-being from using the product, asserting a specific relationship between a disease and an herbal supplement is prohibited unless it is approved by the FDA. In addition, the 1999 amendment by the FDA clearly puts colloidal silver products on a higher level of scrutiny, stating that such products are "not recognized as safe and effective and are misbranded.'' (4)

Although the FDA has made rule modifications based on its awareness of the wide availability of silver-containing products on the Internet, it is clear that average consumers are still inundated with inaccurate information about those products and can easily obtain them. Not only are silver-containing nasal sprays not safe, but they also have not been proven effective in clinical trials.

Conclusion

Information about silver-containing nasal sprays on the Internet is misleading and inaccurate. Consumers are unlikely to easily discover the risk of argyria with long-term use of these products. Despite several measures by the FDA to regulate silver-containing products, they remain widely available. Otolaryngologists should be aware of the misinformation their patients may be receiving about these products and should be able to provide patients with accurate and evidence-based information. More regulation of this industry may be needed to curtail the deceptive information used to market these products.

References

(1.) Hill WR, Pillsbury DM. Argyria: The Pharmacology of Silver. 1st ed. Baltimore: The Williams and Wilkins Co., 1939.

(2.) Frommann C. Ein Fall von Argyria mit Silberabscheidungen im Darm, Leber, Nieren und Milz. Virch Arch Bd 1859:135-47.

(3.) Sataline L. Tarnished silver. Lancet 2004;363(9415):1166.

(4.) 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. Fed Regist 1999;64(158):44653-8.

(5.) Tomi NS, Kranke B, Aberer W. A silver man. Lancet 2004;363(9408): 532.

(6.) Bouts BA. Images in clinical medicine: Argyria. N Engl J Med. 1999; 340(20):1554.

(7.) Bianchi L, Orlandi A, Di Stefani A, et al. "Familial" generalized argyria. Arch Dermatol 2006; 142(6):789-90.

(8.) Wickless SC, Shwayder TA. Medical mystery--the answer. N Engl J Med. 2004;351 (22):2349-50.

(9.) White JM, Powell AM, Brady K, Russell-Jones R. Severe generalized argyria secondary to ingestion of colloidal silver protein. Clin Exp Dermatol 2003;28:254-6.

(10.) Brandt D, Park B, Hoang M, Jacobe HT. Argyria secondary to ingestion of homemade silver solution. J Am Acad Dermatol 2005;53(2 Suppl 1):S105-107.

(11.) McKenna JK, Hull CM, Zone JJ. Argyria associated with colloidal silver supplementation. Int J Dermatol 2003;42(7):549.

(12.) Wadhera A, Fung M. Systemic argyria associated with ingestion of colloidal silver. Dermatol Online J 2005;11 (1):12.

(13.) Fung MC, Bowen DL. Silver products for medical indications: Riskbenefit assessment, J Toxicol Clin Toxicol 1996;34(1):119-26.

(14.) van Hasselt P, Gashe BA, Ahmad J. Colloidal silver as an antimicrobial agent: Fact or fiction? J Wound Care 2004;13(4):154-5.

(15.) Bleehen SS, Gould DJ, Harrington CI, et al. Occupational argyria: Light and electron microscopic studies and X-ray microanalysis. Br J Dermatol 1981;104(1):19-26.

(16.) Massi D, Santucci M. Human generalized argyria: A submicroscopic and X-ray spectroscopic study. Ultrastruct Pathol 1998;22 (1):47-53.

(17.) Gaul LE, Staud AH. Clinical spectroscopy. Seventy cases of generalized argyrosis following organic and colloidal silver medication. JAMA 1935;104:1387-90.

(18.) Drake PL, Hazelwood KJ. Exposure-related health effects of silver and silver compounds: A review. Ann Occup Hyg 2005;49(7):575-85.

(19.) Morris CA, Avorn J. Internet marketing of herbal products. JAMA 2003;290(11):1505-9.

(20.) Ashar BH, Miller RG, Getz KJ, Pichard CR A critical evaluation of Internet marketing of products that contain ephedra. Mayo Clin Proc 2003;78(8):944-6.

Table. Examples of misleading health claims made
on Web sites regarding silver nasal sprays

Kills virtually any germ with which it comes into contact,
has no known side effects, and does not lead to the development
of resistant organisms.

Potent yet nontoxic natural antibiotic proven effective
against 650 different species of bacteria, virus, and fungus.

Safe, effective relief for nasal infections.

This proves lethal to over 650 different diseases, skin
problems, fungi, parasites, molds, and bacterial and viral
conditions but has proven completely nontoxic to the body,
animals, and plants.

This nasal infection formula of 132 ppm of mild silver protein
is highly beneficial for any nasal infection.

Safe and nontoxic, has superior antimicrobial effectiveness
against viral, bacterial, and yeast infections in the nasal
passages. Pain is relieved quickly.

Michael T. Gaslin, MD; Cory Rubin, BA; Edmund A. Pribitkin, MD

From the Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospital, Philadelphia.

Corresponding author: Edmund A. Pribitkin, MD, 925 Chestnut St., 6th Floor, Philadelphia, PA 19107. Phone: [phone]; fax: [phone]; e-mail: [e-mail]