Topical Aloe Vera for Skin and Oral Wounds
January 2001; Volume 4; 8-11
By Susan T. Marcolina, MD
In de materia medica, the greek physician discorides described the use of aloe for treatment of skin wounds, infections, hair loss, and hemorrhoids.1 Traditionally, aloe has been used topically in ointments and creams to assist in the healing of wounds, burns, eczema, and psoriasis.2 Recent clinical and laboratory studies—some positive and some negative—have revealed important information regarding its use for skin and oral wounds.
Botanical Data
Aloe vera (Aloe barbadensis Miller) belongs to the Lily family (Liliaceae). There are approximately 360 different species worldwide. Its name is derived from the Arabic word alloeh meaning shining, bitter substance. This cactus-like succulent grows in hot, dry climates.1
Aloe barbadensis is the only aloe species currently used commercially in cosmetic and medicinal formulations. The mucilaginous tissue in the center of the aloe vera leaf is called aloe vera gel. Medicinal products for wound care are made from this portion of the plant.
The peripheral bundle sheath cells produce a bitter, yellow latex composed largely of phenolic compounds called anthraquinones. This portion of aloe commonly is termed "aloe juice," "aloe sap," or "aloes." Total leaf extracts contain both the gel and the aloes.2,3
Growing season and irrigation affect gel composition such that leaves from well-irrigated plants have less polysaccharide than drier plants.4
Aloe Vera Composition
Aloe vera contains 75 potentially active constituents.1 (See Table 1.) The gel mucopolysaccharides primarily are long-chain sugars of glucose and mannose or glucomannans.5
| Table 1-Chemical constituents of aloe vera/aloes | ||||
| Category | Components | |||
| Vitamins | B1, B2, B6, C, E (alpha-tocopherol), A (beta-carotene), folic acid, choline | |||
| Enzymes | cyclooxygenase, oxidase, amylase, catalase, lipase, alkaline phosphatase, carboxypeptidase | |||
| Inorganic compounds | calcium, sodium, chlorine, manganese, zinc, chromium, copper, magnesium, iron, potassium sorbate |
|||
| Saccharides | cellulose, glucose, mannose, L-rhamnose, aldopentose | |||
| Anthraquinones | aloin, barbaloin, isobarbaoin, anthranol, aloetic acid, ester of cinnamic acid, aloe-emodin, emodin, chrysophanic acid, resistannol |
|||
| Inert substances | lignin | |||
| Amino acids (essential) | lysine, threonine, valine, methoinine, leucine, isoleucine, phenylalanine | |||
| Amino acids (non-essential) | histidine, arginine, hydroxyproline, aspartic acid, glutamic acid, proline, glycerine, alanine, tyrosine |
|||
| Miscellaneous | cholesterol, triglycerides, beta-sitosterol, steroids, uric acid, salicylic acid, gibberellin | |||
| Adapted from: Vogler BK, Ernst E. Aloe vera: A systematic review of its clinical effectiveness. Br J Gen Pract 1999:49:823-828. | ||||
Commercial Formulation
High-performance liquid chromatographic analysis of many commercial aloe products reveals widely differing levels of mucopolysaccharide.6 The gel’s muco- polysaccharides undergo hydrolysis upon exposure to air within several hours. Therefore, once harvested from the plant, aloe must be used or commercially processed to retain its potency.
The International Aloe Science Council was established in 1981 to set standards for aloe gel products and their derivatives.7
Mechanism of Action
Aloe vera contains many pharmacologically active compounds. A carboxypeptidase, present in the extract, is capable of hydrolyzing bradykinin and angiotensin I.8 Magnesium lactate can inhibit histamine decarboxylase, thus acting as an antihistamine.9 Decolorized, or anthra- quinone-free, aloe has been reported to inhibit inflammation to a greater extent than the colorized form.10
Fresh and commercial aloe preparations contain high levels of lectin-like substances. They are hemagglutinating proteins that bind to glycoproteins, decreasing inflammation. Lignin is believed to provide the ability to penetrate the skin.11 Gibberellin, contained in the central gel mucilage, acts as a growth hormone-like substance, decreasing inflammation, but stimulating protein synthesis.12
The gel polysaccharides have been shown to have immunomodulatory properties5 and one such product, acemannan (Carrington Laboratories, Irving Texas) has been used in oral and skin wound therapy.
Regulation
RadiaCare Oral Wound Rinse and Carrasyn® Oral Wound Dressing are two Carrington Laboratories products that contain acemannan. These products are FDA- approved for the treatment of recurrent oral aphthous ulceration, stomatitis, and mucositis.13
Clinical Studies
Radiation Dermatitis. Modern scientific interest in topical use of aloe vera for skin wounds was triggered by a case report of accelerated healing of radiation-induced scalp dermatitis.14
Subsequent human trials have yielded conflicting results. The prevention of radiation-induced skin injuries with a 98% pure aloe vera gel (Fruit of the Earth, Irving, Texas) was examined in a one-year, randomized, controlled, double-blind trial and a follow-up randomized, nonblinded trial.15 In the first trial, Williams et al randomized 194 women receiving radiation therapy for breast cancer to undergo therapy with either topical aloe vera gel or placebo gel applied bid to treatment ports in addition to usual care for both groups. No significant difference was found in the healing of the radiation dermatitis by the two groups. After completion of this trial, it was believed that the placebo gel might have had a beneficial effect on its own because of skin lubrication.
The study then was modified to randomize patients from the same breast cancer population to receive the aloe vera gel or no treatment. For this part of the study, 108 women were randomized into this nonblinded trial for eight months. Again, no significant benefit of aloe vera was found over placebo.15 However, samples of the aloe preparation used in this trial were found to have no mucopolysaccharide content.6
Recurrent Aphthous Stomatitis. A case report published in 1939 reported successful healing of a large, intractable, painful, radiation-induced ulcer over 31/2 months with fresh intraoral aloe vera leaf.16 Oral lesions, most commonly aphthous ulcerations caused by virus and trauma, are uncomfortable and heal within 10 to 14 days.17 Plemons et al initially performed a randomized, double-blind study of 60 patients.18 The placebo group applied Orabase® to their lesions while the treatment group applied Carrisyn Gel Wound Dressing (CGWD) (acemannan hydrogel) to their lesions. The second part of the investigation was an open-label study incorporating an additional group of 30 patients who applied intraoral freeze-dried acemannan hydrogel. A significant difference was demonstrated between each of the experimental groups and the control group regarding healing time, with Group III showing the shortest average healing time and all patients in this group completing the study.
Post-Surgical Wound Healing by Secondary Intention. The use of CGWD mucopolysaccharide hydrogel was investigated in secondary intention healing of surgical wounds. A randomized, controlled, non-blinded trial was performed in 40 women with surgical wounds requiring healing by secondary intention after either cesarean delivery or laparotomy for gynecologic surgery.19 Patients were randomized into two groups. One received standard wound management alone while the treatment group got standard wound care plus the aloe vera gel, which was applied with each dressing change. Twenty-one women completed the study. The mean healing time in the conventional care group was significantly shorter (53 days) than in the aloe vera gel group (83 days).
Pressure Ulcerations. A randomized controlled trial compared the use of CGWD hydrogel product to that of moist saline gauze dressings for pressure ulcers.20 Over a 10-week period, 16 subjects were randomized to the acemannan hydrogel experimental group and 14 subjects were randomized to the saline dressing control group. No significant difference in healing time was observed between experimental and control groups.
Psoriasis. A randomized, double-blind, placebo-controlled, four-week study of 60 patients with mild-to-moderate chronic psoriasis compared the use of a topical aloe vera extract (0.5% in a hydrophilic cream) vs. a placebo cream.21 Each subject applied the creams tid to affected areas. There was a statistically significant difference between the treatment and placebo groups with an 83% cure rate in the aloe vera group compared to a 7% cure rate in the placebo group. The patients subsequently were followed for a 12-month period, during which there were no relapses.
Genital Herpes (Initial Episode). Two randomized, controlled, double-blind clinical trials were conducted on men with an initial episode of herpes genitalis. In the first study, 120 men were randomized into three parallel groups. Each patient applied either aloe vera cream (0.5% extract in hydrophilic cream), aloe vera gel, or placebo cream tid for two weeks. Subjects treated with the aloe cream showed a significantly shorter mean duration of healing than patients treated with the aloe gel or placebo (4.8 days vs. 7.0 days vs. 14.0 days, respectively) and the numbers of cured patients were significantly better for patients treated with aloe preparations than placebo (70%, 30%, and 7.5%, respectively). The second study included 60 men randomized into treatment (aloe vera extract 0.5% in hydrophilic cream) and placebo groups.22 The aloe vera cream treatment significantly curtailed healing time (4.9 days vs. 12 days for placebo, P < 0.001).
Adverse Effects
Aloe vera can cause a local and disseminated hypersensitivity syndrome. Cases of cutaneous hypersensitivity to topical aloe can be confirmed with a patch test.23
Reported side effects include burning,18 contact dermatitis,15 and mild itching.21
Conclusion
The topical application of the acemannan-containing product is efficacious in alleviating the pain of and accelerating the healing of recurrent oral aphthous ulceration and stomatitis.
However, aloe significantly delayed healing in surgical wound healing by secondary intention. Aloe vera topical preparations have not prevented radiation-induced dermatitis. Topical aloe vera may be a useful treatment for genital herpes and psoriasis, but further randomized, controlled, double-blind clinical trials are warranted.
Recommendation
Topical aloe products should be avoided in the treatment of pressure ulcers and surgical wound healing by secondary intention. Their use for psoriasis and genital herpes cannot be recommended currently. There is no evidence that topical aloe vera can prevent radiation-induced dermatitis. Acemannan-containing oral wound products can be used to treat recurrent aphthous ulceration and stomatitis.
Dr. Marcolina is a board-certified internist and geriatrician in Issaquah, WA.
References
1. Vogler BK, Ernst E. Aloe vera: A systematic review of its clinical effectiveness. Br J Gen Pract 1999:49: 823-828.
2. Gottlieb K. Aloe Vera Heals. The Scientific Facts. Denver, CO: Royal Publications; 1980:1-31.
3. Newall CA, et al. Herbal Medicine: A Guide for Health Care Professionals. London: The Pharmaceutical Press; 1996.
4. Yaron A. Characterization of aloe vera gel composition and autodegradation and stabilization of the natural fresh gel. Phytother Res 1993;7:S11-S13.
5. Reynolds T, Dweck AC. Aloe vera leaf gel: A review update. J Ethnopharmacol 1999;68:3-37.
6. Ross SA, et al. Quantitative analysis of aloe vera mucilaginous polysaccharides in commercial aloe vera products. J AOAC Int 1997;80:455-457.
7. Aloe Vera Studies Organization: What to look for. Available at: http://www.aloe-vera.org/howto.htm. Accessed September 20, 2000.
8. Fujita D, et al. Bradykininase activity of aloe extract. Biochem Pharmacol 1976;25:205.
9. Klein AD, Penneys N. Aloe vera. J Am Acad Dermatol 1988;18:714-720.
10. Davis RH, et al. Processed aloe vera administered topically inhibits inflammation. J Am Podiatr Med Assoc 1989;79:395-397.
11. Danhof IE, et al. Stabilized aloe vera: Effect on human skin cells. Drug Cosmet Ind 1983;133:52.
12. Davis RH, Maro NP. Aloe vera and gibberellin. Anti-inflammatory activity in diabetes. J Am Podiatr Med Assoc 1989:79:24-26.
13. Radiacare Oral Wound Rinse. 510(k) No. K964852. Food and Drug Administration; Center for Devices and Radiological Health; Washington DC. Approved March 3, 1997.
14. Collins EE, Collins C. Roentgen dermatitis treated with fresh whole leaf of aloe vera. Am J Roentgenol 1935;33:396.
15. Williams MS, et al. Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity. Int J Radiat Oncol Biol Phys 1996;36:345-349.
16. Mandeville FB. Aloe vera in the treatment of radiation ulcers of mucous membranes. Radiology 1939;32: 598-589.
17. Rennie JS, et al. Recurrent aphthous stomatitis. Br Dent J 1985;159:361-367.
18. Plemons JM, et al. Evaluation of acemannan in the treatment of recurrent aphthous stomatitis. Wounds 1994;6:40-45.
19. Schmidt JM, Greeenspoon JS. Aloe vera dermal wound gel is associated with a delay in wound healing. Obstet Gynecol 1991;78:115-117.
20. Thomas DR, et al. Acemannan hydrogel dressing versus saline dressing for pressure ulcers. Advanc WoundCare 1998;11:273-276.
21. Syed TA, et al. Management of psoriasis with aloe vera extract in a hydrophilic cream: A placebo-controlled, double-blind study. Trop Med Int Health 1996;1: 505-509.
22. Syed TA, et al. Aloe vera extract 0.5% in hydrophilic cream versus aloe vera gel for the management of genital herpes in males. A placebo-controlled, double-blind, comparative study. J Euro Acad Dermatol Venerol 1996;7:294-295.
23. Morrow DM, et al. Hypersensitivity to aloe. Arch Dermatol 1980;116:1064-1065.
January 2001; Volume 4; 8-11
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