Aloe

Aloe vera (syn. A. barbadensis) Family: Asphodelaceae(*)

INTRODUCTION

Aloe species can be found throughout the tropics and warmer regions worldwide. Aloe is thought to have originated in North Africa or the Nile region in Sudan,1 There are approximately 360 species and subspecies of succulent plants (herbs, shrubs, and trees) in the genus Aloe, distributed in Africa, the Arabian Peninsula, and certain islands of the Indian Ocean.( n2, n3) The wild origin of Aloe vera, however, is uncertain.4 The commercially significant aloes are perennials with 15 to 30 fleshy leaves up to 1.5 feet long, 3 to 4 inches across the base, and with saw teeth marking the margins of the leaves.( n1)
HISTORY AND CULTURAL SIGNIFICANCE

Aloe's use dates back almost 6,000 years.( n2) Its uses were first documented on a Mesopotamian clay tablet dating from 2100 BCE and the Ebers Papyrus (ca. 1250 BCE), discovered in Egypt in 1873, listing at least 12 aloe-containing preparations for treating internal and external ailments. In the 1st century CE, the Greek physician Dioscorides (ca. 40-90) recommended it for boils, chapping, genital ulcers, hair loss, hemorrhoids, inflammation, and mouth irritation.( n3) Pliny the Elder (ca. 23-79 CE) and Galen (ca. 130-200 CE) used aloe to treat wounds and gastrointestinal disorders. Additional ancient medicinal uses include treatment for acne, arthritis, burns, dermatitis, headache, high blood pressure, indigestion, peptic ulcers, pruritus (itchy skin caused by various disorders), and psoriasis.( n2) The Egyptian queens Nefertiti and Cleopatra used it as a beauty aid,( n3) and it was used for embalming according to Pliny the Elder.( n5)

Various species of Aloe have long been used to treat constipation, specifically with the anthraquinone-containing latex found in cells inside the leaves. In 1981, the German Commission E approved the use of the latex from A. barbadensis (syn. A. vera) and A. ferox for constipation.( n6) In 2006, the European Medicines Agency (EMEA) published a final monograph on aloe, which' is now relevant for the registration of well-established use herbal medicinal products in all EU Member States. Standardized aloe preparations of European Pharmacopoeia (PhEur) quality are approved by EMEA for short-term use in cases of occasional constipation.( n7)

In North America, in 2008, Canada published 2 final aloe monographs (oral and topical) for the purpose of natural health product (NHP) compendial product license applications. In the final monographs, Health Canada approved the oral use of aloe latex as a stimulant laxative for relief of occasional constipation( n8) and the topical use of the leaf gel to help relieve minor burns including sunburn and to assist healing of minor wounds such as cuts, burns, and minor skin irritations.( n9) In the United States, aloe was included in the first edition of United States Pharmacopoeia (USP) of 1820,( n10) and it remains official in the 33rd revision of the USP in 2010 as an official laxative drug.( n11) However, the US Food and Drug Administration (FDA) banned the use of aloe latex in over-the-counter (OTC) stimulant laxative drugs in the United States in 2002 due to the lack of submission of evidence of safety.( n12) Aloe, however, remains a component of the OTC mucosal protectant drug product Compound Benzoin Tincture USP.( n13) Additionally, aloe dried latex and aloe juice can still be labeled and marketed as dietary supplement products so long as the marketer submits an FDA notification letter attesting that it has substantiation to support the proposed structure/ function claim statements and that the product is manufactured under dietary supplement cGMPs (current good manufacturing practices).

Externally, aloe vera inner leaf, often called "gel," and leaf juice have been used in cosmetics, post-treatment of dermabrasion (treatment of acne scars, tattoos, fine wrinkles, etc. from the skin), to promote wound healing, and to alleviate psoriasis.( n2) In cosmetics, aloe vera juice and gel is added to moisturizers, cleansers, shampoos, suntan lotions, and sunburn treatments. Though other species of Aloe are used in products globally, Aloe vera is believed to be the most widely used species throughout the world.
MODERN RESEARCH

At least 3 human clinical studies have been conducted on aloe vera's effect on psoriasis. Psoriasis is a condition in which the immune system sends faulty signals that accelerates the growth cycle of skin cells via increased DNA turnover. A 2010 randomized (R), comparative, double-blind (DB), 8-week study on 80 patients found topical aloe vera cream (prepared with 70% mucilage by the Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand) to be more effective than 0.1% triamcinolone acetonide in mild to moderate cases.( n14) In a 2005 R, DB, placebo-controlled (PC) trial, 40 patients with psoriasis were treated with either Aloe Vera Gel (98% aloe vera leaf gel, Aloe Vera Group ApS, Søborg, Denmark) or a placebo gel with identical ingredients (i.e., xanthan gum, potassium sorbate, sodium benzoate [SB], sodium sulfite, and citric acid) except for water replacing the aloe. The aloe group experienced a 72.5% improvement while the placebo group experienced an 82.5% improvement.( n15) The surprisingly high response rate in the placebo group indicated to the study's designers that the placebo might have had some effect in its own right that made the aloe gel treatment results seem less effective than placebo. A plausible explanation is that SB works on DNA like drugs used to treat psoriasis, and aloe will bind some of the SB in the aloe preparation, thereby probably reducing the potential beneficial effect of aloe's component acemannan, an immune modulator that works through the DNA.( n16) In a DB, PC study in 1996, 60 patients with psoriasis were self-treated with a 0.5% aloe extract in a hydrophilic cream (50% aloe leaf ethanol extract prepared at the University of the Punjab, Lahore, Pakistan) or placebo 3 times daily for 5 days per week for 4 weeks.17 After 16 weeks, the aloe cream had cleared up the psoriasis symptoms in 25 of 30 patients, compared to 2 of 30 in the placebo group.

Two studies address the effectiveness of aloe against lichen planus, a chronic skin condition characterized by an itchy rash. In one RDBPC trial of 54 patients with oral lichen planus, 22 of 27 patients treated with aloe vera gel (prepared with 70% aloe mucilage by the Faculty of Pharmaceutical Sciences, Khon Kaen University) had a good response after 8 weeks of treatment (compared to 2 of 27 in the placebo-treated group), and 2 had complete clinical remission.( n18) In a RDBPC trial in 2008 of 34 female patients with vulval lichen planus, 14 of 17 patients treated with aloe vera (100% aloe vera gel, NBTY, Ronkonkoma, NY) improved by at least 50% after 8 weeks of treatment, compared to improvement of only 1 of 17 in the placebo group.( n19)

A 2009 randomized, controlled study on 30 patients with 2 same site second degree burns that had occurred within 24 hours were treated twice daily with spray-dried aloe vera powder (0.5 g in cream made with powder obtained from filtrated inner leaf gel, Zarband Phytopharmaceutical, Tehran, Iran) on one site and silver sulfadiazine (SSD) cream on the other. The sites treated with aloe healed approximately 3 days sooner (mean 15.9 ± 2 days) than the SSD-treated sites.( n20) Additionally, a 2006 meta-analysis of 4 studies that explored aloe vera's effects on burns used duration of wound healing as an outcome measure and determined that, despite differences in products and dosages used, aloe might speed up the wound healing process and increase the rate of healing success in first and second degree burns.( n21)

In 2008, a RDBPC study explored the anti-inflammatory properties of aloe leaf gel on 40 volunteers who were irradiated with a 1.5-fold minimal erythema dose of UVB.( n22) The test areas were treated on 2 subsequent days with 97.5% aloe leaf gel (manufacturer not stated), 1% hydrocortisone in placebo gel, or 1% hydrocortisone in cream. The aloe gel significantly reduced UV-induced erythema after 48 hours, performing better than the hydrocortisone in gel but not as well as the hydrocortisone in cream.

An open comparison study in 2003 evaluated dry-coated aloe vera gloves (freeze-dried aloe vera leaf gel dissolved in distilled water to prepare a 25% gel/solution applied to the inner surface of the glove; Aloetouch, Medline Industries Inc., Mundelein, IL) on participants who were factory assembly-line workers with repeated occupation-induced superficial skin trauma.( n23) After 7-17 days (mean time 10.4 days) marked improvement in skin quality (erythema, fissures, and excoriation) of the gloved hands were observed. There was no improvement in the non-gloved hands of any participant.

In a 2002 preliminary open, non-comparative study, crude aloe vera leaf gel was judged to be as effective in the treatment of scabies as was a benzyl benzoate lotion.( n24) A 2006 study concluded that freeze-dried aloe extract added to cosmetic formulations improves skin hydration.( n25)

A small clinical trial in 2006 explored changes in urine composition in children after consuming aloe.( n26) Thirteen healthy male volunteers between the ages of 9 and 13 ingested 100 g of freshly prepared aloe leaf gel twice a day for 7 consecutive days. Based on composition of urine samples taken throughout the trial, the authors concluded that aloe gel consumption has the potential to prevent kidney stone formation in children.

In a 2004 DBRPC study, 44 hospital outpatients between the ages of 18 and 80 with mild to moderately active ulcerative colitis and no recent changes in conventional prophylactic therapy were randomly given 100 mL twice daily of an aloe vera leaf gel liquid (n=30; formulation not stated, Forever Living Products, Jersey, Channel Islands) or a placebo liquid (n=14) for 4 weeks.( n27) In the patients who took the aloe, 30% (n=9) experienced clinical remission, 37% (n=11) experienced improvement, and 47% (n=14) responded to the treatment but did not have significant improvement--compared to 7% (n=l), 7% (n=1), and 14% (n=2) respectively in the placebo group. The authors concluded that oral aloe gel taken for 4 weeks produced a clinical response more often than placebo, reduced the histological (cellular) disease activity, and appeared to be safe.

A number of studies have also been conducted using acemannan, an acetylated polymannose identified in the 1980s as a primary active component in aloe vera leaf gel.( n2) Clinical studies have shown its efficacy in acceleration of wound healing in postderm-abrasion, partial thickness of wounds, and pressure ulcers. Freeze-dried acemannan was also shown to be effective against painful dry socket treatment as a result of dental procedure complications.( n28) Acemannan has also shown benefit in the reduction in AIDS symptoms, synergism and/or no interference with AZT, in improved quality of life and morphologic alterations in HIV patients, and in preventing virus penetration and stimulating the immune system.( n2) Acemannan has also shown promise in in vitro and in vivo studies for managing cancer with no toxicity or adverse side effects. Injectable acemannan is indicated in dogs and cats for use as an aid in treatment and clinical management of fibrosarcoma.( n29) However, some aloe processing techniques remove much if not all of the acemannan, possibly explaining some of the inconsistent effects of commercial aloe products.

In 1998, the US National Toxicology Program (NTP) published an Executive Summary on "Aloe Vera Gel," raising safety concerns about oral aloe products due to the mutagenic properties of one of aloe's anthraquinone constituents, 1,8-dihydroxyanthracene. However, the summary also stated that most aloe products sold for oral consumption in dietary supplements have reduced quantities of 1,8-dihydroxyanthracene.( n30)

Aloe-related chronic toxicity studies were conducted in rodents by the NTP.( n31) The first study used "Aloe Vera Gel" with a much higher anthraquinone content than is normally found in commercial aloe products. The anthraquinone in aloe (called aloe emodin) is a powerful stimulant laxative. The high doses caused diarrhea, weight loss, and malnutrition. Chronic diarrhea reduces the short-chain fatty acid (SCFA) content in the colon, and SCFAs enable the body to resist colon cancer.( n32) The toxicity observed in the first study would be expected from a lifetime of chronic diarrhea.

Aloe vera, as a component of dietary supplement products, is the subject of ongoing research by FDA Division of Biochemical Toxicology.( n33)
FUTURE OUTLOOK

The main cultivation areas for aloe vera include Africa (e.g., KwaZulu-Natal), the West Indies, Netherland Antilles (Curaçao), South America (coastal Venezuela), North America (Mexico, Florida, Texas, and Arizona), India (hot dry valleys of northwestern Himalaya, coasts of Bombay, Gujarat, and southern India), and China. The Chinese aloe industry has grown rapidly in recent years and plans to become a major player in the global aloe market.( n34)

Due to confusion in the labeling of products, the International Aloe Science Council (IASC) has recommended that all aloe vera products manufactured for sale worldwide* use the Standardized Common Name "aloe vera" and specify the plant part (i.e., leaf if the leaf is used in its entirety, inner leaf, or aloe latex).( n35) IASC recommends that manufacturers refrain from using the term "whole leaf" and use aloe vera leaf gel/juice/capsules etc. as appropriate. IASC also recommends that aloe vera juice be labeled with the actual percentage of juice in the product along with additional ingredients, that it specify if the juice is reconstituted or from concentrate, and that the quantitative concentration level be clearly specified.

(*) The genus Aloe has been classified/reclassified according to recent taxonomic investigations into several different families, e.g., Aloaceae, Liliaceae, Xanthorrhoeaceae et al., i.e., depending on the source. ABC currently uses the GRIN (Germplasm Resources Information Network) database at the US Department of Agriculture as the primary authority on botanical nomenclature and related taxonomic issues.

†Regarding use of the term "worldwide," it should be noted that this is a recommendation of a national trade association. Governmental agencies may have other specific nomenclature requirements for the labeling of aloe-containing medicinal products, whether oral or topical. In many countries, aloe latex and/ or aloe gel are regulated as active pharmaceutical ingredients and, therefore, the labeling of the medicinal product must use the identical nomenclature as provided in the official monograph for which the product license or registration was based. Such labeling may or may not always match the recommendation of a national trade association.

PHOTO (COLOR): Aloe Aloe vera Photo ©2010 Steven Foster

PHOTO (COLOR): Aloe Aloe vera Photo ©2010 Steven Foster
REFERENCES

(n1.) Grindlay D, Reynolds T. The aloe vera phenomenon: a review of the properties and modern uses of the leaf parenchymagel. Journal of Ethnopharmacology. 1986;16:117-51.

(n2.) McAnalley BH. The Science Behind Aloe: The Healing Plant. Grand Prairie, TX: Bill McAnalley & Assoc.; 2009.

(n3.) Mascola N, Izzo AA, Borrelli F, Capasso R, et al. Healing powers of aloes. In: Reynolds T. Aloes: Thegenus Aloe. Boca Raton, FL: CRC Press; 2004:211-238.

(n4.) CITES. Review of significant trade: East African Aloes. Geneva, Switzerland: Convention on International Trade in Endangered Species. 2003: Available at: http://www.cites.org/eng/com/PC/14/EPC 14-09-02-02-A4.pdf.

(n5.) Goldberg A. Aloe: Aloe spp. Botanical Booklet Series #315. Austin, TX: American Botanical Council; 1999.

(n6.) Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW, Rister RS, eds. Klein S, Rister RS, trans. The Complete German Commission E Monographs Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston: Integrative Medicine Communication; 1998.

(n7.) EMEA HMPC. Final Community Herbal Monograph on Aloe barbadensis Miller and on Aloe (various species, mainly Aloe ferox Miller and its hybrids). London, UK: European Medicines Agency Committee on Herbal Medicinal Products. September 7, 2006. Available at: www.ema.europa.eu/pdfs/human/hmpc/ aloe/7631006enfin.pdf.

(n8.) NHPD. Aloe - Oral. In: NHPD Compendium of Monographs. Ottawa, Ontario: Natural Health Products Directorate. October 31, 2008. Available at: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/ monoReq.do?id=4&lang=eng.

(n9.) NHPD. Aloe - Topical. In: NHPD Compendium of Monographs. Ottawa, Ontario: Natural Health Products Directorate. October 31, 2008. Available at: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/ monoReq.do?id=5&lang=eng.

(n10.) The Pharmacopoeia of the United States of America, 1820, by the authority of the medical societies and colleges. Boston: Wells and Lilly, for Charles Ewer, 1820.

(n11.) States Pharmacopeial Convention. Aloe. In: USP 33-NF 28. Rockville, MD: United States Pharmacopeial Convention. 2010.

(n12.) Bayne H. FDA issues final rule banning use of aloe and Cascara sagrada in OTC drug products. HerbalGram. 2002;56:56.

(n13.) Food and Drug Administration. 21 CFR Part 310--Status of Certain Additional Over-the-Counter Drug Category II and II Active Ingredients. Final rule. Federal Register. May 9, 2002;67(90):31125-31127. Available at: www.fda.gov/downloads/ Drugs/DevelopmentApprovalProcess/DevelopmentResources/ Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm094018.pdf.

(n14.) Choonhakarn C, Busaracome P, Sripanidkulchai B, Sarakarn P. A prospective, randomized clinical trial comparing topical aloe vera with 0.1% triamcinolone acetonide in mild to moderate plaque psoriasis. J Eur Acad Dermatol Venereol. 2010;24(2): 168-172.

(n15.) Paulsen E, Korsholm L, Brandrup F. A double-blind, placebo-controlled study of a commercial Aloe vera gel in the treatment of slight to moderate psoriasis vulgaris. J Eur Acad Dermatol Venereol. 2005; 19 (3):326-331.

(n16.) Piper PW. Yeast superoxide dismutase mutants reveal a pro-oxidant action of weak organic acid food preservatives. Free Rad Bio Med. 1999;27(11/12):1219-1227.

(n17.) Syed TA, Ahmad SA, Holt AH, Ahmad SA, et al. Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled, double-blind study. Tropical Medicine and International Health. 1996; 1 (4):505-509.

(n18.) Choonhakarn C, Busaracome P,, Sripanidkulchai B, Sarakarn P. The efficacy of aloe vera gel in the treatment of oral lichen planus: a randomized controlled trial. Br J Dermatol. 2008; 158(3):573-577.

(n19.) Rajar UDM, Majeed R, Parveen N, Sheikh I, Sushel C. Efficacy of aloe vera gel in the treatment of vulval lichen planus. J Coll Physicians Surg Pak. 2008; 18(10):612-614.

(n20.) Khorasani G, Hosseinimehr SJ, Azadbakht M, Zamani A, Mahdavi MR. Aloe versus silver sulfadiazine creams for second-degree burns: a randomized controlled study. Surgery Today. 2009;39(7):587-591.

(n21.) Maenthaisong R, Chaiyakunapruk N, Niruntraporn S, Kongkaew C. The efficacy of aloe vera used for burn wound healing: a systematic review. Burns. 2007;33(6):713-718.

(n22.) Reuter J, Jocher A, Stump J, Grossjohann B, Franke G, Schempp CM. Investigation of the anti-inflammatory potential of Aloe vera gel (97.5%) in the ultraviolet erythema test. Skin Pharmacol Physiol. 2008;21:106-110.

(n23.) West DP, Zhu YF. Evaluation of aloe vera gel gloves in the treatment of dry skin associated with Occupational exposure. Am J Infect Control. 2003;31 (1):40-42.

(n24.) Oyelami OA, Onayemi A, Oyedeji OA, Adeyemi LA. Preliminary study of effectiveness of Aloe vera fin scabies treatment. Phytother Res. 2009;23(10):1482-1484.

(n25.) Dal'Belo SE, Gaspar LR, Maia Campos PM. Moisturizing effect of cosmetic formulations containing aloe vera extract in different concentrations assessed by skin bioengineering techniques. Skin Res Technol. 2006; 12(4):241-24.

(n26.) Kirdpon S, Kirdpon W, Airarat W, Thepsuthammarat K, Nanakom S. Changes in urinary compositions among children after consuming prepared oral doses of aloe (Aloe vera Linn). J Med Assoc Thai. 2006;89(8): 1199-1205.

(n27.) Langmead L, Feakins RM, Goldthorpe S, et al. Randomized, double-blind, placebo-controlled trial of oral aloe vera gel for active ulcerative colitis. Aliment Pharmacol Ther. 2004; 19(7):739-747.

(n28.) Poor MR, Hall JE, Poor AS. Reduction in the incidence of alveolar osteitis in patients treated with the SaliCept patch, containing Acemannan hydrogel. J Oral Maxillofac Surg. 2002;60(4):374-379.

(n29.) USDA. Veterinary Biological Products: Licensees and Permittees. December 2009. USDA website. 2009. Available at: www.aphis.usda.gov/animal%5f health/vet_biologics/publications/CurrentProdCodeBook.pdf. Accessed June 24, 2010.

(n30.) National Toxicology Program. Executive Summary - Aloe Vera. Research Triangle Park, NC; National Toxicology Program; 1998.

(n31.) National Toxicology Program. NTP toxicology and carcinogenesis studies of EMODIN (CAS NO. 518-82-1) feed studies in F344/N rats and B6C3F1 mice. Natl Toxicol Program Tech Rep Ser. June 2001 ;493; 1-278. Available at: http://ntp.niehs.nih.gov/ntp/htdocs/ LT_rpts/tr493.pdf. Accessed June 8, 2010.

(n32.) Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and non-starch polysaccharides. Physiol Rev. 2001; 81(3):1031-1064.

(n33.) Beland FA. Biochemical Toxicology. Available at: www.fda.gov/ AboutFDA/CentersOffices/NCTR/WhatWeDo/ResearchDivisions/ ucm078482.htm. Accessed June 24, 2010.

(n34.) Brinckmann J. Aloes. Market News Service for Medicinal Plants & Extracts. 2002; Nr. 4

(n35.) International Aloe Science Council. IASC Labeling Guidance. Silver Spring, MD: International Aloe Science Council; 2010.

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By Gayle Engels

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