As far as I know there is still no evidence that bacteria can develop resistance to iodine... :)
Although it has been speculated that iodine delays healing and is cytotoxic, there is substantial evidence to suggest that the commonly-used low concentration, slow release iodophors improve healing rates and are effective as highly potent antimicrobials with a broad spectrum of activity, including antibiotic-resistant strains such as MRSA.
Authors: Sibbald RG, Leaper DJ, Queen D.
Full author details can be found on page 4.
What is iodine?
Iodine is a natural dark violet, non-metallic element that plays a key role in human metabolism. It is essential for the production of thyroid hormones and an iodine deficiency can result in hypothyroidism. Iodine occurs naturally in the form of iodide ions in sea water, fish, oysters and certain seaweeds. It can also be found in vegetables grown in iodine-rich soil and dairy products. It has been described as 'the most potent antiseptic available'.
What is the history of iodine in wound healing?
In the 4th century BC, before iodine had been discovered, Theophrastus, a pupil of Aristotle, recorded that iodine-rich seaweeds could be used to reduce the pain of sunburn . One of the first antiseptic iodine preparations to be used in wound care was Lugol's solution containing elemental iodine and potassium in water, which was developed in 1829. This solution was also used to treat wounds in the American Civil War.
The antimicrobial properties of iodine were first demonstrated in 1882 by Davaine6. In the First World War, iodine was found by Alexander Fleming to reduce the incidence of gas gangrene in the wounds of soldiers when compared to carbolic acid . Since the mid-19th century, iodine-based preparations have also had an important role in the prevention of surgical site infections. Povidone iodine preparations are popularly used as an antiseptic to prepare the patient's skin before surgery and are also used by surgeons and theatre staff as a skin cleanser and antiseptic in preoperative hand scrubs.
Early uses of iodine involved aqueous and alcoholic iodine preparations, which were associated with unpleasant side effects including pain, irritation and skin staining.
Why is iodine safer today?
Iodophors were developed in the 1950s to overcome the side effects associated with elemental iodine. These were found to be safer and less painful, but just as effective as elemental iodine, allowing widespread use.
Bonding iodine with another molecule makes it less toxic and instead of high concentrations of iodine being released in a single application, the iodine is slowly released from the reservoir carrier molecule over a sustained period of time.
Iodophors are preparations that bind iodine to a solubilising agent or carrier. The water-soluble complex allows the slow release of a low concentration of free iodine when the carrier comes into contact with wound exudate. This controlled release of low concentrations of iodine helps to minimise the negative side effects of using free elemental iodine.
Modern iodine preparations
The two most commonly used iodophors in modern wound dressings (Table 1) are:
Povidone iodine preparations were introduced in the 1960s and it is now the most common iodophor in clinical use. It is available in different formulations, including solution, cream, ointment, spray and wound dressings.
What is the evidence to support iodine use?
There is extensive evidence to support the use of povidone iodine in wound healing  (Table 2), but its use is not without controversy due to perceived issues with toxicity, systemic absorption and delayed healing. It has been suggested that iodine has a negative impact on cells involved in the wound healing process and because of this its safety and efficacy have been questioned.
Some reviews have analysed the conflicting evidence and have found that studies based on animal models tend to support the argument for iodine's cytotoxicity, whereas human studies suggest that PVP-I can help the wound healing process by reducing bacterial load and decreasing infection rates [9,10]. One study demonstrated that not only does PVP-1 significantly improve the healing rates of chronic venous leg ulcers, but also that it lacks cytotoxicity in vivo .
The efficacy of cadexomer iodine has been demonstrated using both animal models and clinical studies. Cadexomer iodine was found to significantly reduce symptoms associated with infection (eg exudate, erythema, oedema and pain) in patients with pressure ulcers  and venous leg ulcers .
In addition to providing an antimicrobial effect, in vitro studies have reported a lack of toxicity for human fibroblast activity  and that cadexomer iodine may increase epithelialisation of chronic wounds [15,16]. However, its mode of action is not understood and further research is needed to determine whether wound aetiology has a contributory role .
How does iodine work as an antimicrobial?
Iodine's exact antimicrobial mode of action is not fully understood, but it is believed to be associated with its ability to rapidly penetrate the cell wall of micro-organisms.
Schreier et al also investigated the effects of PVP-1 on microbial cells and found that it affects the structure and functions of enzymes and cell proteins and damages bacterial cell function by blocking hydrogen bonding and altering the membrane structure. These multiple modes of action ensure the rapid death of microbes and help to prevent the development of bacterial resistance. Because the microbicidal action of iodine is related to several directly toxic effects on the cell wall, rather than through specific molecular pathways (as used by antibiotics), resistance is highly unlikely and reports of iodine-resistant strains are exceptionally rare (Figure 1).
Is iodine effective against MRSA?
There is substantial in vitro evidence demonstrating that PVP-I is a highly effective and broad spectrum antimicrobial. Activity has been demonstrated against both common bacterial wound isolates[18,19[ and antibiotic-resistant species20. Lacey and Catto determined that more than 99% of meticillin-resistant Staphylococcus aureus (MRSA) cells were killed within 10 seconds of exposure to PVP-I. Mertz et al found that cadexomer iodine significantly reduced MRSA and total bacteria in partial thickness porcine wounds compared with a no-treatment control and a vehicle group.
Is iodine effective against biofilms?
At the most basic level, a biofilm can be described as being bacteria embedded in a slimy, protective mucopolysaccharide glycocalyx. The effectiveness of iodine in the management of biofilm is currently unclear, although it is known that low dose, slow release iodine is effective in killing free-floating planktonic micro-organisms and is therefore likely to be a good choice of antiseptic dressing when the intention is to suppress biofilm formation or prevent recontamination.
Recent evidence suggests that sustained release iodine may penetrate biofilms more effectively than silver or polyhexamethylene biguanide (PHMB).
Can patients build up bacterial resistance to iodine?
Despite 170 years of prolonged and extensive use of iodine in medicine and wound care, iodine-resistant microbial strains are exceptionally rare.
The validity of the one documented case of resistance to iodine products26 has been questioned and the methodology of the study criticised.
When is iodine indicated?
An international consensus document on managing wound infection, recommends the use of antiseptic dressings as being part of an overall management plan in the following circumstances:
Slow release iodine dressings have been used to treat a range of wound types where infection is present or suspected.
These include pressure ulcers, venous leg ulcers, diabetic foot ulcers, minor burns and superficial skin-loss injuries[24,28].
When are iodine dressings contraindicated?
Iodine dressings must be used under medical supervision in patients with thyroid diseases, known or suspected iodine sensitivity, in pregnant or breastfeeding women or in newborn babies and up to the age of six months8.
Long-term use of PVP-I has been loosely associated with mild hyperthyroidism and long-term use is not recommended for patients with impaired thyroid function. However, a number of studies have monitored thyroid function during PVP-I clinical trials and have reported that it remains unchanged[30-32].
To avoid toxicity or the hypothetical risk of thyroid-related complications, iodine products should be used with caution in children, in those with large burn areas, and where prolonged treatment of large open wounds is required. The use of iodine dressings should also be avoided before and after the use of radio-iodine diagnostic tests (until permanent healing).
Reports of systemic effects following short-term PVP-I treatment are extremely rare. Iodine absorption has been found to be dependent on the size of the wound and the duration of treatment. Hunt et al also discovered a relationship between wound area and iodine levels in serum and urine following the treatment of burn wounds with PVP-I, but it was proposed that renal function was a factor in the determination of this. Iodine should, therefore be avoided in patients with significant renal disease.
How to apply iodine dressings
The method of application depends on the mode of delivery. Dressings should be applied directly to the surface of the wound and covered using a secondary dressing as appropriate. All dressings should be applied according to the manufacturer's instructions for use.
Why does iodine stain the skin brown?
The skin is sometimes stained brown after treatment with iodine products. This is because of the effects of the tri-iodide ion and, to a lesser extent, free molecular iodine.
However, any staining that may occur is harmless and will quickly fade.
Why does the application of iodine sometimes sting?
Iodine-based products can be associated with a transient burning or stinging sensation immediately after they are applied to open wounds. However, this is not harmful. The stinging probably relates to the osmotic loads delivered by higher concentrations of iodine in some preparations.
The prevalence of allergic reactions to the topical application of iodine varies considerably (between 0.7% and 41%), depending on which study is reviewed.
For example, in a dermatological study by Juhász35 involving 50 patients, no cases of sensitisation to PVP-I after patch-testing were recorded.
How frequently should dressings be changed
The slow release of the iodine in these preparations allows the wound to remain in continuous contact with the antiseptic, whereas with a single exposure to a product such as PVP-I tulle the iodine is soon broken down[36,37]. It is important to remember that even with modern iodine dressings (eg Inadine, Iodosorb and Iodoflex), which provide a slow release of iodine, this is only for a relatively short time and frequent dressing changes are required to constantly replenish the supply of antiseptic to the wound. It is assumed that once the dressing has lost its 'colour' the antiseptic effect has been lost and the dressing should be changed.
In heavily exudating wounds, dressings may need to be changed daily. With appropriate moisture balance iodine dressings can be applied 1-3 times per week.
When should treatment be discontinued?
Medical supervision should be sought if using iodine for more than one week. Treatment should be re-evaluated regularly and discontinued when the signs of infection resolve and the wound is healing.
If the wound does not improve after 10-14 days, the patient and the wound should be re-evaluated and an alternative antiseptic dressing regimen or systemic treatment with an antibiotic considered.
What are the economic arguments for iodine?
Povidone iodine dressings and irrigating solutions are relatively inexpensive compared to other antimicrobial therapies. Dressings that lose their colour (eg Inadine) may be more cost-effective in that they provide an indicator of how frequently dressings should be changed.
Iodine and the future
Iodine-containing dressings may be developed that combine the antimicrobial effect of iodine with autolytic debridement, moisture balance and active therapies to optimise wound healing.
Although it has been speculated that iodine delays healing and is cytotoxic, there is substantial evidence to suggest that the commonly-used low concentration, slow release iodophors improve healing rates and are effective as highly potent antimicrobials with a broad spectrum of activity, including antibiotic-resistant strains such as MRSA. It is unfortunate that the concerns about iodine are based on studies that are so varied in method and design that it is difficult to draw reliable comparisons and conclusions. The reputation of iodine wound products, used as antimicrobials, suffered as a result of these studies but it is now widely accepted that slow-releasing iodophor antimicrobials are safe and have minimal detrimental impact on wound healing.
To cite this publication
Sibbald RG, Leaoer DJ, Queen D. Iodine Made Easy. Wounds International 2011; 2(2): Available from http://www.woundsinternational.com
Sibbald RG, Leaper DJ, Queen D.
1. Professor of Public Health Sciences and Medicine, University of Toronto, Toronto, Ontario, Canada
2. Visiting Professor, Department of Dermatology and Wound Healing, Cardiff University, Cardiff, UK
3. Honorary Research Fellow, Department of Dermatology and Wound Healing, Cardiff University, Cardiff, UK
Healthcare practitioners are advised to consult the package inserts for any iodine-based products before applying the dressing to a wound.
This article is supported by an educational grant from Systagenix. The views expressed in this 'Made Easy' section do not necessarily reflect those of Systagenix.
This article has been posted so many times but it's so good~!
Topic: Disappearing Iodine Test
A Reader Writes:
A friend of mine was just diagnosed with a possible thyroid disorder (her test was in the form of a drop of iodine on her arm and watching how fast it disappeared). Her chiropractor suggested she start off by taking something called Thyroid Helper which can be found at ..... Have you ever heard of this and do you know how effective it might be?
David Derry Responds:
The "test" of putting iodine on the skin to watch how fast it disappears is not an indicator of anything. The iodine disappearance rate is unrelated to thyroid disease or even iodine content of the body.(1-2) Meticulous research by Nyiri and Jannitti in 1932 showed clearly when iodine is applied to the skin in almost any form, 50% evaporates into the air within 2 hours and between 75 and 80 percent evaporates into the air within 24 hours. (1) A total of 88 percent evaporates within 3 days and it is at this point that the evaporation stops. The remaining 12 percent that is absorbed into the skin has several fates. Only 1-4% of the total iodine applied to the skin is absorbed into the blood stream within the first few hours. The rest of the iodine within the skin (8-11%) is slowly released from the skin into the blood stream.
However Nyiri and Jannitti's findings that “The percentage of iodine penetration through the skin is the same, irrespective of whether the cells have a high or low vitality, or are dead, and irrespective of the direction of penetration" have important implications for iodine functions in the body, skin, pregnancy and fetus and also for the therapeutic use of topical and oral iodine. Iodine would be the only compound of significance during early pregnancy which can pass rapidly through all tissues of the fetus without the aid of any blood vessel or lymphatic transport. It could be that not only does iodine control natural cell death (apoptosis) (5) in the fetus but may also influences stem cell development.
Nyiri and Jannetti also mentioned iodine applied on the skin can be used to shrink swelling of the thyroid gland (goiters). So even small amounts of iodine absorbed through the skin can have good effects on body organs. From my own clinical experience, repeated application of iodine (Lugol’s) to the skin appears to cause regeneration of the skin from the bottom up (Quiescent, stable or stem cell) (3) eventually sloughing the old version of the skin off like a snake molting. If there was a pre-cancerous lesion on the old skin, it is replaced with new skin minus the lesion. There does not seem to be any skin lesions which are not helped or cured by this procedure. In some cases I found clinically obvious low thyroid conditions also needed to be treated to be more effective. Minor lacerations and healing of surgical wounds respond well. If skin regeneration is from the bottom, then there is little or no scar formation.
My parents’ generation tended to put tincture of iodine onto a fresh wound to prevent infection. This turns out to be helpful but not the best way to use it. Besides it stung badly when applied. It is much more effective (and doesn't hurt) to apply iodine repeatedly after a scab has been formed. The iodine put onto the scab helps to organize total repair of the tissue. It is implied a similar approach could be taken to burns of all depths but at the same time the physiology of burns suggest there is an acute lack of thyroid hormone. (3)
All pre-malignant lesions and many other oddities of the skin appear to respond to this regeneration process triggered by topical iodine. I have mentioned previously a patient with a biopsy-proven breast cancer lesion (she refused surgery because of previous cancer treatment) that was strongly fixed to the skin responding well to topical iodine and ended up being a dimple on the breast three year later. (6)
It is my belief a water solution of iodine (like Lugol's) is an important therapeutic agent for skin. Because of its effectiveness and the results, perhaps many skin diseases are related to local tissue areas of relative iodine deficiency. Perhaps the most graphic lesions are the "keloid" (worm) incision scars formed after surgical procedures. If the iodine intake and tissue levels are adequate, such as in Japan, keloid formation doesn't happen (7). In addition, iodine's ability to trigger natural cell death (apoptosis) (5) makes it effective against all pre-cancerous skin lesions and likely many cancerous lesions. The local site is replaced with normal skin. However, even lesser doses of topical iodine seem to reverse the ominous appearance of skin lesions. Because my older brother died of metastatic melanoma, my chances of getting a malignant melanoma are increased by 400 times. (8-9) Having grown up in Venezuela near the equator my sun exposure at a young age was far above normal. So all suspicious lesions I notice are returned to normal with topical Lugol's.
One of the most famous of documentations of iodine skin therapy to a famous person occurred in the American Civil War.
"On September 29, 1862, Colonel John B. Gordon held the center of General Lee's army at the battle of Antietam, or Sharpsburg. The first volley from the northern lines sent a ball through the calf of Gordon's right leg; soon after, another went through the muscles of his thigh; a third pierced his left arm, tearing asunder the tendons and mangling the flesh; a forth ripped through his shoulder leaving a wad of clothing embedded in its track. Still, no bones were broken; but, while Gordon lingered in the firing line, "with", as he says himself, "but little of my usual strength", a fifth ball struck him squarely in the face.
Dr. Weatherly of the 6th Alabama Regiment, in charge of medical arrangements, had the Colonel removed to a base hospital, and prescribed tincture of iodine to be painted on the wounds three or four times a day. The case was unpromising. Gordon's eyelids were greatly swollen; one eye was completely closed, the other almost so; his jaw was immovably clenched, and, to make matters worse, erysipelas (staphylococcus infection of skin) had set in on the left arm.
Mrs. Gordon, his wife, who nursed him - her name was Fanny, and she was then a beautiful girl of 25 - put a liberal interpretation on her instructions and painted the wounds, not three or four times a day, but, as Gordon himself says: "I think three to four hundred time a day." Fanny's diligence and devotion were rewarded. Her husband survived, outlived the war, became the Governor of Georgia, a General, and Commander-in-Chief of the United Confederate Veterans. He died in 1904." (10)
I think Fanny knew iodine applied often was a more effective way to deliver iodine to the body especially applied on multiple sites. Likely Gordon's iodine blood levels and tissue levels rose throughout his body. As iodine is by far the best antibiotic, antiviral and antiseptic of all time, the colonel's body defenses were able to gain control of the infections. At the same time local repeated application to the wound sites caused the skin to grow up from its bottom where all the cells (Stem cells) that make normal skin are residing. Likely this minimized or eliminated scar formation. Thus Nyiri’s and Jannetti’s studies confirm why Fanny’s method of treatment worked so brilliantly. Some of our recent serious skin diseases such a "flesh-eating disease" should respond quickly to topical iodine treatment practiced by Fanny. Or, for another example, iodine put onto a mosquito bite would kill all bacteria and viruses at the site of the bite within 10-30 seconds making it impossible for any virus or bacteria to multiply and get started --such as in West Nile Fever. Naturally, this applies to tic bites (Lyme's disease) as well. For many decades in the 1800s people carried around little bottles of iodine around their necks to use on all occasions. People in mosquito and tic infested areas should think of doing this again. (8) In addition, it has been forgotten vaporized iodine rapidly kills air borne viruses such as polio and SARS viruses.. Used extensively in the forties and fifties it may be of use to explore this approach again.
There has been no significant clinical research on iodine therapy or use for 40 years. (11-15) I feel it is important for research to be directed at this potentially significant area of medical treatment. It is worth noting the greatest part of significant research with iodine was done before the Medline search facilities were available. Of course, since large doses of iodine are tolerated intravenously without side effects, it has yet to be explored what help this may have for many cancer patients or even other diseases.
I hope these concepts help.
1. Nyiri,W., Jannitti,M.. About the fate of free iodine upon application to the unbroken animal skin. J Pharmacol Exp Ther 45:85-107, 1932.
2. Biskind,M.S. Penetration through tissue of iodine in different solvents. Proc Soc Exp Biol Med 30:35-37, 1932.
3. Robbins pathologic basis of disease. Eds Cotran,R.S., Kumar,V., Collins,T. Sixth Edition W.B. Saunders Company, Philadelphia. 1999. Page 91. and page 434.
4. Gershenfeld,L. Iodine Editor Reddish.G.F. Antiseptics, disinfectants fungicides and chemical and physical sterilization, Philadelphia:Lea & FebigerHa, 1957. pages 223 277.
5. Derry,D.M. One hour lecture: Iodine, thyroid hormone and breast cancer. How to prevent and survive breast cancer. World Breast Cancer Conference, Victoria BC June 4-6, 2002..
6. Derry, DM. Breast cancer and iodine How to prevent and survive it. Trafford Publishing Victoria, Canada. 2001 page 89.
7. Updegraff,H.L. Reconstructive surgery and old facial burns. JAMA 101:1138-1140, 1933. page 1139
8. Clark WH. The nature of cancer: morphogenesis and progressive (self ) disorganization in neoplastic development and progression. Acta Oncol 1995; 34:3-21.
9. Clark WH. Tumour progression and the nature of cancer. J Cancer 1991; 64:631-644. 10. Kelly,F.C.. Iodine in medicine and pharmacy since its discovery--1811-1961. Proc R Soc Med 54:831-836, 1961.
11. Wayne,E.J,. Koutras,D.A.. Alexander,W.D.. Clinical aspects of iodine metabolism, Philadelphia:F.A. Davis Company, 1964.
12. Braverman,L.E.. Iodine and the thyroid: 33 years of study. Thyroid 4 (3):351-356, 1994.
13. Vagenakis,A.G.. Effects of iodides: clinical studies. Thyroid 1 (1):59-63, 1990.
14. Paul,T., Meyers,B., Witorsch,R.J., Pino,S., Chipkin,S., Ingbar,S.H. Braverman,L.E.. The effect of small increases in dietary iodine on thyroid function in euthyroid subjects. Metabolism. 37:121-124, 1988.
15. Zaichick,V. Zaichick.S.. Normal human intrathyroidal iodine. Science of the Total Environment 206 (1):39-56, 1997.
a couple of studies...
Inactivation of Aeromonas hydrophila by iodine
Arunsri Tachushong (Mahidol Univ., Bangkok (Thailand). Ramathibodi Hospital Nursing Dept); Kriengsak Saitanu
Conference Symposium on Fresh Water Fishes Epidemic: 1982-1983, Bangkok (Thailand), 23-24 Jun 1983
Date of publication 1983
AGRIS Categories Animal diseases
AGROVOC French terms Poisson d'eau douce; Aeromonas hydrophila; Iode; Desinfectant; Efficacite
AGROVOC Spanish terms Peces de agua dulce; Aeromonas hydrophila; Yodo; Desinfectantes; Eficacia
Notes 2 ill. Summaries (En, Th)
Source Proceedings of Fresh Water Fishes Epidemic 1982-1983, Chulalongkorn Univ., Bangkok (Thailand). Research Affairs.- Bangkok (Thailand), 1983. p. 386-393
Abstract (English) Rate of bactericidal by iodine of Aeromonas hydrophila was carried out using different concentrations, at pH 7 under and dirty condition. Under clean condition, iodine at concentration 25, 12.5 and 6.25 ppm could killed 2x107 cells/ml. of A. hydrophila within 1 minute. However, 1 ppm of iodine reduced the titer of bacteria by 4 log unit in 1 min. The lowest concentration tested, 0.1 ppm could not killed the organisms. Under dirty condition, 25, 12.5 10 and 8 ppm could killed 4x107 cells/ml. of organisms with in 1 minute. But the lower concentrations, 6.25, 1 and 0.1 ppm could not reduced the number of tested bacteria, except only 6.25 ppm reduced the titer of bacteria by 1 log unit in 1 minutes.
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Efficacy and Toxicity of Iodine Disinfection of Atlantic Salmon Eggs
Authors: Chalupnicki, Marc A.1; Ketola, H. George1; Starliper, Clifford E.2; Gallagher, Dennis3
Source: North American Journal of Aquaculture, Volume 73, Number 2, 1 April 2011 , pp. 124-128(5)
Publisher: Taylor and Francis Ltd
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Recent interest in the restoration of Atlantic salmon Salmo salar in the Great Lakes has given rise to new culture techniques and management programs designed to reduce pathogen transmission while stabilizing and enhancing wild populations. We examined the toxicity of iodine to Atlantic salmon eggs and its effectiveness as a disinfectant against bacteria on egg surfaces. We spawned and fertilized eight gravid Atlantic salmon from Cayuga Lake, New York, and exposed their eggs to 10 concentrations of iodine (5, 10, 50, 75, 100, 500, 750, 1,000, 5,000, and 7,500 mg/L) for 30 min during water hardening. An additional subsample of unfertilized eggs was also exposed to some of the same concentrations of iodine (5, 10, 50, 75, and 100 mg/L) to determine the efficiency of disinfection. Viable eggs were only obtained from four females. Survival of eggs to the eyed stage and hatch tended to be reduced at iodine concentrations of 50 and 75 mg/L and was significantly reduced at concentrations of 100 mg/L iodine or more. We calculated the concentrations of iodine that killed 50% of the Atlantic salmon eggs at eye-up and hatch to be 175 and 85 mg/L, respectively. Aeromonas veronii, A. schubertii, A. hydrophila, A. caviae, Plesiomonas shiggeloides, and Citrobacter spp. were the predominant bacteria present on the surface of green eggs and were significantly reduced by an iodine immersion. The use of iodine as a disinfectant on Atlantic salmon eggs was effective at low concentrations (50-75 mg/L), for which toxicity to Atlantic salmon was minimal.