amr Review Article Bugs as Drugs, Part 1: Insects. The “New” Alternative Medicine for the 21st Century? E. Paul Cherniack, MD Abstract estimates that $20 billion will be needed to replace Insects and insect-derived products have been widely used in the shortage of 800,000 conventional health care folk healing in many parts of the world since ancient times. workers by 2015.1 Globally ubiquitous, arthropods Promising treatments have at least preliminarily been studied potentially provide a cheap, plentiful supply of experimentally. Maggots and honey have been used to heal healing substances in an economically challenged chronic and post-surgical wounds and have been shown to be world. comparable to conventional dressings in numerous settings. Honey has also been applied to treat burns. Honey has been Maggots combined with beeswax in the care of several dermatologic The most well-studied medical application of disorders, including psoriasis, atopic dermatitis, tinea, arthropods is the use of maggots – the larvae of pityriasis versicolor, and diaper dermatitis. Royal jelly has flies (most frequently that of Lucilia sericata, a been used to treat postmenopausal symptoms. Bee and ant blowfly) that feed on necrotic tissue.2 Traditional venom have reduced the number of swollen joints in patients healers from many parts of the world including with rheumatoid arthritis. Propolis, a hive sealant made by Asia, South America, and Australia have used bees, has been utilized to cure aphthous stomatitis. “larval therapy,”3 and records of physician use of Cantharidin, a derivative of the bodies of blister beetles, has maggots to heal wounds have existed since the been applied to treat warts and molluscum contagiosum. Middle Ages.3 Figure 1 depicts maggots on a wound. Combining insects with conventional treatments may provide Fly larvae aid in wound healing via a number of further benefit. mechanisms: (1) larval secretions break the larger (Altern Med Rev 2010;15(2):124-135) adhesion molecules, fibronectin and collagen, into smaller fragments that promote fibroblast aggrega- tion and tissue repair;4 (2) larvae eat necrotic tissue E. Paul Cherniack, MD – The Introduction: Why Insects? that would otherwise form a nidus for infection, Geriatrics Institute, University Insects and other arthropods provide ingredi- liquefying such tissue and aiding its digestion;4 (3) of Miami Miller School of Medicine, Division of ents that have been a staple of traditional medicine maggots release antibacterial substances, some of Geriatrics and Gerontology, and for centuries in parts of East Asia, Africa, and which are produced by Proteus mirabilis bacteria the Geriatrics and Extended South America. While many of these ingredients that live naturally in the larval intestine; and (4) Care Service and Geriatric 3 Research Education, and have not been evaluated experimentally, an ingested bacteria are destroyed within maggots. Clinical Center (GRECC) of increasing number have been shown in preliminary Maggots commercially grown under sterile the Miami Veterans Affairs trials to have beneficial properties. Although conditions are used in wound healing. In one Medical Center Correspondence address: medical practitioners in more economically robust application technique, a hole is cut in a hydrocol- Miami VA Medical Center, countries may prefer conventional treatments, it loid dressing over a wound.3 The maggots are lifted Room 1D200, 1201 NW 16th may be more a result of squeamishness rather than out of a container on a piece of nylon netting, Street, Miami, FL 33125 Email: evan.cherniack@ science. Furthermore, in parts of the world where which is folded together and taped onto the va.gov conventional medical care is scarcer than arthro- dressing over the hole after removal of the mois- pods used by folk healers, insects may represent a ture in the maggot growth medium. A piece of feasible substitute in some cases. In sub-Saharan gauze is placed over the nylon and taped in place.3 Africa alone, the World Health Organization Volume 15, Number 2 Alternative Medicine Review 124 Copyright © 2010 Alternative Medicine Review, LLC. All Rights Reserved. No Reprint Without Written Permission. Review Article amr Key words: maggots, honey, Larval therapy has also been evaluated in wounds, surgery, burns, bee, propolis, cantharidin, Figure 1. Maggots on a Wound controlled trials. In a randomized trial, 267 molluscum, ant, beetle, subjects with venous or arterial ulcers at least pityriasis, royal jelly, ulcers, 25-percent covered with necrotic material were larva, tinea assigned to receive maggots or a conventional hydrogel dressing.11 Although there was no difference in rate or timing of healing between groups, the maggot-treated wounds were debrided significantly faster (2.31 days; p<0.001). On the other hand, subjects treated with maggots had a significantly higher pain score (approximately 40 points higher on a 150-point analog scale; p<0001). In another trial involving diabetic leg ulcers, non-healing wounds were treated with either maggots, a conventional hydrogel, or the conven- tional therapy followed by larval treatment.12 In one study, maggots were grown in vitro and Wounds treated with maggots had significantly less placed in the wounds of 30 individuals after necrotic tissue after two weeks. Thus, there is bacterial swabs of the wounds were taken.5 The limited evidence that larval therapy can provide patients had arterial or venous stasis ulcers, wound healing for lower extremity ulcers compa- diabetic or pressure ulcers, or chronic postopera- rable to conventional treatment. A systematic tive wounds. Secretions taken either from maggots review concluded that, in appropriate patients, use grown on sterile plates or from wound sites may be safe and effective.13 Maggots may be sampled from 1-5 days after the introduction of appropriate especially when conventional therapies larvae were studied for antibacterial properties. cannot be used, or in parts of the world where Larval secretions successfully suppressed larvae are more easily obtainable than conven- Staphylococcus aureus growth in vitro. In vivo, 51 tional treatment. wounds (83.2%) healed, with reduced bacterial counts within the wounds. Honey Treatment Maggots were also used to treat chronic leg Honey is another insect-derived substance that wounds in several patient series. In one case series has been used in wound healing and for treatment involving 34 leg wounds of at least three months of other disorders, such as infections and irritable duration in subjects ages 32-84, 85 percent of the bowel syndrome. Therapeutic effects of honey have wounds healed.6 Of the healed wounds, 93 percent been documented from ancient times and it is still resolved within 7-10 days. In a second series, 70 used in African folk medicine.14,15 Honey composi- patients, ages 25-94 with wounds of at least six tion varies widely throughout the world depending weeks duration, were given treatment with on the species of bee and plants the bees feed on, one-day-old larvae added at a concentration of both of which influence the honey’s antioxidant 5-10 larvae/cm2.2 Eighty-six percent of the subjects and antimicrobial properties.16-18 Four phenolic had a 66- to 100-percent reduction of wound size. compounds in honey – p-hydroxybenzoic acid, During treatment, 35 percent of subjects perceived naringenin, pinocembrin, and chrysin – are more pain, 25 percent less pain, and 46 percent no antimicrobials and antioxidants. The carbohydrate difference in pain. In a third case series, larval in honey is also antimicrobial.16,17 Honey also has therapy was applied to 70 chronic wounds; 43 antimutagenic properties.19 percent of the wounds were completely debrided, and 29 percent were partially debrided.7 There are Wound Healing also case reports of the successful use of maggots The best studied use of honey is for wound for treating the wound of a terminally ill patient8 healing. Honey promotes wound healing through and for non-healing venous ulcers.9 osmotic properties that serve to moisturize the One study examined the factors that predict wound bed and reduce the risk of maceration. It better outcomes of larval therapy in a series of 117 also works via anti-inflammatory processes that wounds. Greater wound depth, older patient age, reduce exudate and inhibit fibrin that adheres and presence of septic arthritis portended a worse eschar to the wound bed, impairing tissue repair.20 outcome.10 125 Alternative Medicine Review Volume 15, Number 2 Copyright © 2010 Alternative Medicine Review, LLC. All Rights Reserved. No Reprint Without Written Permission. amr Review Article Honey has been used to heal wounds in numer- Burns ous situations. Many studies have found dressings Several studies, most conducted by the same that contain honey comparable to conventional investigator, have examined the use of honey in the dressings. In a randomized, double-blind, placebo- treatment of burns. In one randomized, controlled controlled trial, 100 patients who had toenail trial, 104 subjects with burns covering 5-40 percent surgery were assigned to receive either a honey- of their bodies were divided into two groups. One had coated dressing or a conventional paraffin dress- 15-30 mL undiluted honey applied to the burn, the ing.21 There was no significant difference between other received a conventional topical cream of silver groups in days taken to heal the wounds. sulfadiazine applied to gauze covering the burn.29 However, in a single-blind study (blind to the Subjects