Honey is a sweet substance that is synthesized biotechnologically from flower nectars by bees. It is the first natural sweetener known to humanity. Bees have been living in our world for about 56 million years. Honey is defined as the most complex beverage produced by insects. As a result of chemical and biochemical analyzes, honey is shown to contain 181 different molecules.
Interestingly, the therapeutic properties of honey have been documented in the world’s oldest medical literature. In 2000 BC, Sumerian and Egyptian physicians used honey for the treatment of open and closed wounds, ulcers, eye diseases, lungs, skin and especially stomach and bowel diseases. The Chinese, Indians, Greeks, and Romans were reported to have done similar practices. Even Hippocrates (460-377 BC), known as the “father of modern medicine,” used honey in the treatment of various diseases. The Muslim physician Ibn-i Sina (980-1037), known as Avicenna as the King of Medicine, wrote dozens of prescriptions containing honey in his book, the Medicine Law – al-Kanun fit-Tıb. In particular, Ibn Sina used a mixture of honey and flour paste known as “tapitma” as a wound dressing.
Honey in Wound Treatment
In addition to being a source of nutrients and energy, honey is a health potion and a healing occasion for the treatment of various diseases. Honey, royal jelly and pollen produced by bees became important pharmaceuticals in the period when the tendency to move away from chemical drugs increased. Honey, pollen, propolis, royal jelly, and bee venom are used in the treatment of many diseases. Research in recent years has shown that honey is also very effective in wound treatment.
In parallel, today ‘apitherapy’ bee products and treatment methods have shown rapid development and apitherapy centers have been established. Although the use of honey in wound treatment goes back to 2000 BC, the effect of honey on wound treatment until the twentieth century has not been explained by scientific evidence. Recent studies have shown that honey inhibits the growth of bacteria, which has spread its use in the treatment of wounds.
The Role of Honey in Wound Healing
The effect of honey in wound treatment occurs as the reduction of inflammatory edema, cleansing the wound, accelerating the excretion of dead tissues, energizing the cell locally and protecting the protein layer on the wound. Honey also has the ability to remove odors from wounds. This is due to the fact that inflammatory bacteria leave the wound and prefer honey, a rich source of glucose. The bacteria that attack the honey are eliminated because of the germicidal properties of honey. Honey has antibacterial properties attributed to its high osmolarity (the movement of water on both sides of the semipermeable membrane due to the difference in concentration of substances that do not pass through the membrane) and its acidity, hydrogen peroxide (H2O2 = oxygenated water). This high osmolarity in honey attracts lymph fluid; The substances dissolved in this liquid have a nourishing effect on the regenerated tissues.
H2O2 and glycolic acid (the principal acid found in honey), which has an important place in wounds cleaning, is produced by glucose oxidase, which is naturally present in honey. H2O2, which has significant antibacterial properties in honey, is found at harmlessly low levels. The concentration of H2O2 deposited within one hour is approximately one-thousandth of that of the H2O2 solution, which is generally used as an antiseptic. Pure unpasteurized honey contains about 40% glucose, 40% fructose and 20% water and a small number of amino acids, group B vitamins, enzymes such as diastase, invertase, glucose oxidase, and catalase, as well as potassium, iron, magnesium, phosphorus, copper, and calcium minerals. Honey, which is created as an excellent energy source, also forms a liquid barrier to prevent the wound from becoming infected and has a hygroscopic effect that regulates the edema.
Honey also contains high levels of antioxidants that protect wound tissues from oxygen radicals produced by H2O2. Low levels of H2O2 stimulate new vessel formation and proliferation of connective tissue. This new vessel formation also increases oxygen supply to the tissues. Surface acidification of wounds has been shown to accelerate wound healing. Therefore, its low pH (3.6 or 3.7) increases the antibacterial effect of honey and accelerates wound healing. The bees have been tasked with producing honey by taking advantage of many different flowers in their inspired ways. The antimicrobial activity of honey varies greatly depending on the source and the process in which it is subjected. The antibacterial effect may vary up to a hundred times depending on the flower species in honey composition. Honey with high antibacterial activity produced in certain regions is used for the treatment of inflammatory wounds, resulting in better results.
Honey Treatment for Open Wounds
By gathering high nutritional substances from thousands of fruits and flowers, bees can produce a source of healing food such as honey. In a study of mice, clean, open wounds were treated with unpasteurized honey or saline (FTS), which showed a reduction in wounds 3, 6 and 9 days after wound formation. In all cases where honey was used, it was observed that the wound was smaller, granulation tissue was better and upper skin cells increased on the 6th and 9th days. It was proved that wound healing was faster than the control group and that the honey applied to the wounds had no side effects.
In another study, it was observed that 58 of 59 patients whose wound did not heal by known methods recovered by treatment using natural honey. Wounds were caused by bacteria in 51 of these patients, but not bacterial in 8 patients. One week after treatment with honey, the wounds were sterile (free from bacteria). In all patients, it was seen that the dead and gangrenous tissues were gradually separated from the wall of the wound site and removed with a holding device and the patient did not feel any pain. It was observed that the edema surrounding the wound disappeared and odor formation decreased in wounds that were dressed with honey. In addition, it was revealed that the dead tissues were rapidly regenerated with granulation tissue and the upper skin cells increased.
Honey has also been used successfully in the treatment of burn wounds. In a study of 92 patients with second-degree burns, it was found that wounds treated with honey-impregnated gauze healed earlier than wounds treated with polyurethane film, and wound infection was much less. The honey-impregnated gauze was prepared by dipping it from the hive and into the untreated honey. In these patients, the wound healed approximately 11 days. In the control group, moisture-permeable, polyurethane dressing was applied and wound healing was performed on average in 15 days.
In a similar study of burn wounds in humans, treatment with honey was compared with silver sulfadiazine (SSD), a wound ointment. The study showed that the rate of recovery was faster in patients receiving honey treatment. Wounds were healed in 51–60 days in patients treated with SSD, but healed in 31–40 days in patients treated with honey. 39 of the 43 inflamed wounds in the honey-treated group became sterile within 7 days. When compared with the SSD group, this number was found to be quite high. In the SSD group, only 3 out of 41 patients were found to be sterile within 7 days. As a result, less irritation (allergic itching) and less pain were observed in honey treatment compared to SSD group; honey shortened the treatment process, was found to be more effective in the treatment of wounds on the surface of the skin.
In another study, it was observed that 21 of 25 patients with burn wounds treated with honey recovered in 7 days, and 18 of 25 patients recovered in the SSD group. In honey treated wounds, there were no scars and no edema, and in the SSD group, scarring remained. The histological examination of honey-treated burn tissues showed a reduction in acute inflammatory changes, inflammation control, and early repair activities compared with SSD. It is recommended to use untreated honey in wound treatment. No side effects were observed due to the application of honey. Honey is easy to apply and low cost compared to medication treatment makes it attractive for wound treatment. It is worth noting that individuals who are not experts in the subject, who do not know which wounds and doses of which honey to apply, are not recommended to perform such applications on their own. Otherwise, an adverse result may be obtained.
Use of Honey in Wound Healing
The use of honey in wound healing has been known and practiced for centuries. Russian soldiers with gunshot wounds during World War II were reported to have been treated with honey. Since then, reports of clinical trials on the efficacy of honey usage in wound treatment have been increasing. In each of these cases, honey has received very positive feedback in terms of its effectiveness compared to modern conventional treatment.
In 1988, Efem et al. Presented the first large-scale wound management clinical observation study in Nigeria and reported that honey treatment was successful in 58 out of 59 wounds and ulcers with conventional treatment. One of the main reasons for the failure of wounds and ulcers to heal is infections caused by microorganisms. If the microorganisms also have drug resistance, the situation worsens. In this study, bacteria were isolated from the wounds of all patients admitted to the clinical study and colonized in culture medium before starting honey treatment. Fourteen different types of microorganisms were isolated, two of which were methicillin-resistant (MRSA and MRSE). In the third week of topical honey application, all pathogenic microorganisms (including resistant bacteria) in the wound were found to be eradicated. Therefore, honey has been shown to have an outstanding antibacterial property. Similar results have been reported by different researchers.
The efficacy of honey in the sterilization of wounds is an important factor contributing to the wound healing process. In our previous study, we have shown that Malaysian honey has antibacterial activity and we have identified organic antibacterial factors in honey. In addition, since honey has a high sugar concentration in its natural form, honey has been shown to have a strong osmotic effect that dries bacterial cells. Absorption of edema and extinction is another important wound healing factor due to the hygroscopic properties of honey. In this way, the surface area of the wound is reduced and the wound is better defined and treated more easily.
Honey’s slightly acidic environment (pH 3.5) delays the growth of bacteria. In studies, it was shown that the growth of the standard bacteria Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) in bacterial culture medium decreased when exposed to acidic pH of 3.5. The preferred growth medium of these pathogenic bacteria is in the pH range 6.0-7.0.
However, when honey is diluted, two important factors appear to play an active role in wound healing. Unprocessed natural honey contains glucose oxidase, an enzyme produced by honey bees. This enzyme catalyzes the reaction of glucose and water to release hydrogen peroxide and gluconic acid into the medium. The resulting hydrogen peroxide level is not toxic to skin cells but is sufficient to kill pathogenic bacteria, and this release continues for a long time.
The second important factor is organic antibacterial compounds such as flavonoids, polyphenols, glycosides and phenolic acids in honey. Phenolic acids exhibit strong antioxidant properties by taking part in the suppression of free radicals that may occur during the healing process. In addition, phenolic acids have been shown to have anti-inflammatory activity. In this animal model study, it is shown that the edema in the back of the rats extinguished in a short time. The combination of all these compounds reveals the antibacterial and antioxidant potential of honey.
The deodorization of the wound in a short time has shown that the goal of honey treatment is not only to improve the wound condition but also to help the patient’s overall well-being. When the wounds initially become free of bacteria, the natural wound healing process begins. However, in all of our clinical observation studies, wound healing has taken place at an amazing rate, demonstrating the unique properties of honey. The honey dressing has been shown to promote angiogenesis (new blood vessel formation). Release of hydrogen peroxide at low concentrations may stimulate angiogenesis and fibroblast development. Honey was also shown to stimulate fibroblast proliferation in cultured fibroblasts.
The fact that advanced perfused tissue can receive nutrient and oxygen supplements for its own use in the healing process is an important step in healing. Angiogenesis helps prevent amputation or extensive radical excision of tissues at risk for ischemic damage and gangrene formation due to low perfusion. Thus, honey used in the study saved diabetic gangrene patients from amputation.
Compared with conventional therapy (povidine-iodine treatment), honey dressing did not dry the wound. Daily cleaning of honey-treated wounds was carried out easily and painlessly, as the dressing materials can be easily peeled off without sticking to the injured areas. Thus, the newly formed tissues were not damaged during the cleaning process. The wounds were maintained in moisture and sterilized with honey. For exposed bones, honey provided the necessary moisture to keep the bones intact. Honey stimulates granulation tissues to close the bones with extraordinary speed. Simple fistula treatment with honey has also been successful. Small amounts of honey were injected into the fistula and the fistula healed within 2 weeks.
The presence of various micronutrients (amino acids, vitamins, minerals, and trace elements), as well as the abundance of easily digestible sugar in honey, have been shown to increase the nutrition of injured tissues. An animal model study conducted by our group showed remarkable biochemical changes in honey-treated wounds. There was a statistically significant increase in DNA, collagen uronic acid and hexominase contents of granulation tissues when compared with the control group. Wound contraction and epithelialization rate were found to be statistically significant in the honey treated group when compared with the control group.
Another factor in the healing process is the state of hydrogen peroxide, which aids in the entry of glucose into the cell. Hydrogen peroxide has been shown to stimulate tyrosine phosphorylation of the insulin receptor and tyrosine kinase activity in intact cells. It has been demonstrated that the sugar content of honey does not adversely affect the blood glucose level of diabetic patients, and patients with difficult-to-control diabetes and ulcers have become controlled after successful sterilization using honey.
Impaired, interrupted wound healing is a common and costly problem for people with diabetes. The number of non-healing diabetic foot ulcers includes 25-50% of all diabetic hospital admissions and most of the 60,000-70,000 amputations in the United States annually. Approximately 15% of all diabetic patients develop one or more foot ulcers, and 15-25% of them eventually require amputation. 43% of our patients complained of diabetic foot ulcers and wounds that did not heal up to 2 years. These ulcers and wounds of honey dressings were completely healed in the studies conducted. The average cost of treating a single infected ulcer in the US is $ 17,000. The cost of using honey dressing with the dry dressing procedure is estimated to be less than $ 2,000. Thus, it can be stated that honey dressing is a more convenient and economical method for health centers all over the world.
In all cases, no allergic reactions or side effects from honey dressing were observed. The role of honey in our observations in wound debridement, wound deodorization, absorption of edema fluids, and nutrition and development are consistent with the article published by Efem.
A Research on Wound Healing Properties of Honey
To date, many scientific and clinical studies have been conducted to prove the miraculous healing properties of honey. Doctors and surgeons have used honey in certain medical practices and have explicitly recommended their use to their patients. Among the examples of recent use of honey can be mentioned are as follows: Professor Smirnov, in the treatment of serious weapon injuries; Dr. Cavanagh et al., In the treatment of critical surgical wounds; Dr. Blomfield in the treatment of ulcers, surface injuries, cuts and abrasions; Dr. Haffejee and Prof. Moosa in the treatment of bacterial gastroenteritis (diarrhea); Dr. Efem in the treatment of severe long-term wounds and ulcers in a wide range of areas; Dr. MacInerney has been involved in the treatment of infected wounds at the vulvectomy site, infected perineal and abdominal wall injuries, and scar tissue tears in the abdominal wall. In each of these cases, the efficacy of honey in the treatment was emphasized in comparison with the “modern-classical” treatment.
With the emergence of antibiotic-resistant microbial species, wound management has become problematic. Modern wound dressings do not provide the expected results, especially in the treatment of chronic, complicated and infected wounds. In this study, the efficacy of honey dressing in chronic wounds and ulcers that cannot be cured by conventional-conventional treatments is shown. The study was conducted at the Malaya University Type Center, one of the most well-equipped and competent medical schools in Malaysia. In line with the results of our study, strong evidence-based findings were obtained for the medical use of honey, a unique natural product.
A total of 57 male and 45 female patients were treated with honey dressing. As a result of the cultures performed before the honey bandage of all wounds, the presence of infection at the initial stage was shown. In the 3rd week of the honey dressing, no infection was observed in the cultures made from all wounds. Wound debridement was performed in 50 patients, amputation was performed in 33 patients, incision and drainage in 9 patients, surgical removal of knees and implants in 3 patients, skin transplantation in 2 patients and flap replacement in 1 patient, angiogram and total knee replacement. applications. One of the interesting observations in this study was that the daily cleaning of the wound site was painless. Because the honey dressing material did not stick to the wounded area and could be easily removed from the wound site. Honey, moisture absorbing and high sugar density features such as the wound area of the cells and neighboring tissues have allowed water to be drawn. This is less inconvenient compared to conventional-conventional wound dressings which tend to adhere to the wound site during the dressing process of the patients. This non-adherent feature of honey significantly reduced the damage of new tissues formed at the wound site.
Effective wound healing was observed in all patients. The majority of the patients were discharged in the third week. Granulation tissue developed in situ of necrotic (dead) tissues and smelly wounds turned into odorless. Honey was also observed to reduce edema around the wound. Many patients with diabetic wounds were treated with small skin transplants and saved from amputation. Honey produced no allergic reactions or other side effects in any of the patients treated. This was the first study at the University of Malaya with 100% success.