Health Care Professional Information

Scientific Name
Aloe vera, Aloe barbadensis, Aloe capensis
Common Name

Aloe gel, aloe leaf

Clinical Summary

Aloe vera is a tropical plant used in traditional medicine throughout the world. It has been studied for its ability to relieve constipation, heal wounds, treat psoriasis, frostbite, ulcerative colitis, diabetes, and burns.
Aloe demonstrated antioxidant and anti-inflammatory properties (9) and Aloe vera cream was shown to be superior to silver sulfadiazine creams for the treatment of second-degree burns (21).
Studies also suggest that constituents of aloe, such as acemannan, aloeride, and di(2-ethylhexyl)phthalate (DEHP) have immunomodulating and anticancer effects (5) (7) (8). Emodin from Aloe vera inhibited cell proliferation and induced apoptosis in human liver cancer cell lines through p53- and p21-dependent pathways (4).
Concurrent administration of aloe with chemotherapy may prevent oral mucositis in patients receiving chemotherapy (23) and benefit those with metastatic cancers (20). Data on external use of aloe products to alleviate radiation-induced skin damage are inconsistent (1) (2) (3). More research is needed.

Purported Uses
  • Burns
  • Cold sores
  • Colitis
  • Diabetes
  • Dry Skin
  • Inflammation
  • Pain
  • Pruritus
Constituents
  • Mono- and polysaccharides
  • Tannins
  • Sterols
  • Organic acids
  • Enzymes
  • Saponins
  • Vitamins
  • Minerals
  • Glucomannan, acemannan
  • Emodin
  • Lipids: cholesterol, gamolenic acid
    (18) (16)
Mechanism of Action

Several studies have been conducted to explore the mechanism of action of aloe. It is presently believed that some of the beneficial effects of aloe result from inhibition of bradykinin by a contained carboxypeptidase. Aloe is also thought to hinder the formation of thromboxane, the activity of which is detrimental to healing of burn wounds (17). Laxative effect of aloe juice and aloe latex is caused by anthraquinone glycosides aloin A and B (16).
Oligosaccharides isolated from aloe extracts were found to prevent ultraviolet radiation-induced suppression of delayed type hypersensitivity by reducing keratinocyte derived immunosuppressive cytokines (25). A polymer fraction of aloe was shown to protect the gastric mucosa against ethanol-induced gastric damage by decreasing mRNA expression levels of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and matrix metalloproteinase (MMP-9). The three enzymes are critical biomarkers in gastric ulceration (26). According to another study, the radio-protective effects of aloe polysaccharides are most likely due to inhibition of apoptosis (27).
Some studies have indicated that Aloe vera may have anticancer effects. Emodin, an extract of Aloe vera, can inhibit cell proliferation and induce apoptosis in human liver cancer cell lines through p53- and p21-dependent pathway (4). Acemannan, a carbohydrate fraction derived from Aloe vera leaf, can stimulate cytokine production in mouse macrophage cell line (5). It also exhibited immunomodulating activity by inducing maturation of dendritic cells (6). Another in vitro study has indicated aloeride, a polysaccharide obtained from aloe vera juice, as a potent immunostimulator by increasing NF-kappa B activities (7). A compound, di(2-ethylhexyl)phthalate (DEHP), isolated from Aloe vera can inhibit leukemic cells in vitro (8).

Warnings

Aloe gel should not be confused with aloe juice or aloe latex, both of which contain anthraquinone, a cathartic laxative. Aloe taken for internal use should be discouraged due to possible adverse effects and inconclusive clinical data. Aloe injections for cancer patients have resulted in several deaths.
The FDA rules that aloe is not safe as a stimulant laxative.
(14)

Adverse Reactions
  • Topical administration of aloe gel is considered safe but oral consumption of aloe can cause gastrointestinal upset and electrolyte abnormalities.
  • Inappropriate use of aloe supplements has been linked to thyroid dysfunction (10), acute hepatitis (11), and perioperative bleeding (12).
  • A case of hypokalemia has been reported with use of aloe vera during chemotherapy (19).
  • Three cases of toxic hepatitis were reported following use of aloe preparations. Liver function was normalized after discontinuing aloe (22).
  • Long term exposure to Aloe vera can cause cancer in animals (28) .
Herb-Drug Interactions
  • Cytochrome P450 substrates: In vitro, aloe juice was found to inhibit CYP3A4 and CYP2D6 and can affect the intracellular concentration of drugs metabolized by these enzymes (24).
  • Sevoflurane: Aloe may have additive antiplatelet effects causing excessive bleeding during surgery (12).
Literature Summary and Critique

Worthington HV, Clarkson JE, Bryan G, et al. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2011 Apr 13;(4):CD000978.
This review included 131 studies involving 10,514 randomised subjects. Ten interventions, where there was more than one trial, showed some statistically significant evidence of a benefit for preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. The treatments were aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate.
However, the strength of evidence varied and benefits may be specific for certain cancers and treatment. Well designed trials are needed to establish the above findings.
 
 

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References
  1. Heggie S, Bryant GP, Tripcony L, Keller J, Rose P, Glendenning M, et al. A Phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue. Cancer Nurs. 2002 Dec;25(6):442-51.
  2. Olsen DL, Raub W, Jr., Bradley C, Johnson M, Macias JL, Love V, et al. The effect of aloe vera gel/mild soap versus mild soap alone in preventing skin reactions in patients undergoing radiation therapy. Oncol Nurs Forum. 2001 Apr;28(3):543-7.
  3. Williams MS, Burk M, Loprinzi CL, Hill M, Schomberg PJ, Nearhood K, 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 Sep 1;36(2):345-9.
  4. Kuo PL, Lin TC, Lin CC. The antiproliferative activity of aloe-emodin is through p53-dependent and p21-dependent apoptotic pathway in human hepatoma cell lines. Life Sci. 2002 Sep 6;71(16):1879-92
  5. Zhang L, Tizard IR. Activation of a mouse macrophage cell line by acemannan: the major carbohydrate fraction from Aloe vera gel. Immunopharmacology. 1996 Nov;35(2):119-28.
  6. Lee JK, Lee MK, Yun YP, Kim Y, Kim JS, Kim YS, et al. Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells. Int Immunopharmacol. 2001 Jul;1(7):1275-84.
  7. Pugh N, Ross SA, ElSohly MA, Pasco DS. Characterization of Aloeride, a new high-molecular-weight polysaccharide from Aloe vera with potent immunostimulatory activity. J Agric Food Chem. 2001 Feb;49(2):1030-4.
  8. Lee KH, Kim JH, Lim DS, Kim CH. Anti-leukaemic and anti-mutagenic effects of di(2-ethylhexyl)phthalate isolated from Aloe vera Linne. J Pharm Pharmacol. 2000 May;52(5):593-8.
  9. Yagi A, Kabash A, Okamura N, Haraguchi H, Moustafa SM, Khalifa TI. Antioxidant, free radical scavenging and anti-inflammatory effects of aloesin derivatives in Aloe vera. Planta medica. 2002 Nov;68(11):957-60.
  10. Pigatto PD, Guzzi G. Aloe linked to thyroid dysfunction. Archives of medical research. 2005 Sep-Oct;36(5):608.
  11. Rabe C, Musch A, Schirmacher P, Kruis W, Hoffmann R. Acute hepatitis induced by an Aloe vera preparation: a case report. World J Gastroenterol. 2005 Jan 14;11(2):303-4.
  12. Lee A, Chui PT, Aun CS, Gin T, Lau AS. Possible interaction between sevoflurane and Aloe vera. Ann Pharmacother. 2004 Oct;38(10):1651-4.
  13. Anon. License revoked for aloe vera use. Nat Med Law 1998;1:1-2.
  14. FDA. Status of Certain Additional Over-the-Counter Drug Category II and III Active Ingredients. http://www.fda.gov/ohrms/dockets/98fr/050902a.htm. Accessed June 15, 2012.
  15. Brinker F. Herb Contraindications and Drug Interactions, 3rd ed. Sandy (OR): Eclectic Med; 2001.
  16. Robbers JE, et al. Pharmacognosy and pharmacobiotechnology. Baltimore: Williams & Wilkins; 1996.
  17. Foster S, et al. Tyler's Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies. New York: Haworth Herbal Press; 1999.
  18. Tyler, V. Herbs of Choice, the Therapeutical Use of Phytomedicinals. Binghamton, New York: Pharmaceutical Press; 1994.
  19. Baretta Z, Ghiotto C, Marino D, Jirillo A. Aloe-induced hypokalemia in a patient with breast cancer during chemotherapy. Ann Oncol 2009 Aug;20(8):1445-6.
  20. Lissoni P, Rovelli F, Brivio F, et al. A randomized study of chemotherapy versus biochemotherapy with chemotherapy plus Aloe arborescens in patients with metastatic cancer. In Vivo. 2009 Jan-Feb;23(1):171-5.
  21. Khorasani G, Hosseinimehr SJ, Azadbakht M, Zamani A, Mahdavi MR. Aloe versus silver sulfadiazine creams for second-degree burns: a randomized controlled study. Surg Today. 2009;39(7):587-91.
  22. Yang HN, Kim DJ, Kim YM, et al. Aloe-induced toxic hepatitis. J Korean Med Sci. 2010 Mar;25(3):492-5.
  23. Worthington HV, Clarkson JE, Bryan G, et al. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2011 Apr 13;(4):CD000978.
  24. Djuv A, Nilsen OG. Aloe Vera Juice: IC(50) and Dual Mechanistic Inhibition of CYP3A4 and CYP2D6. Phytother Res. 2011 Aug 15. doi: 10.1002/ptr.3564.
  25. Byeon SW, Pelley RP, Ullrich SE, et al. Aloe barbadensis extracts reduce the production of interleukin-10 after exposure to ultraviolet radiation. J Invest Dermatol. 1998 May;110(5):811-7.
  26. Park CH, Nam DY, Son HU, et al. Polymer fraction of Aloe vera exhibits a protective activity on ethanol-induced gastric lesions. Int J Mol Med. 2011 Apr;27(4):511-8.
  27. Wang ZW, Zhou JM, Huang ZS, et al. Aloe polysaccharides mediated radioprotective effect through the inhibition of apoptosis. J Radiat Res. 2004 Sep;45(3):447-54.
  28. Toxicology and Carinogenesis Studies of a Nondecolorized Whole Leaf Extract of Aloe Barbadensis Miller (Aloe Vera) in F344/N Rats and B6C3F1 Mice. National Toxicology Program Technical Report. NIH Publication No. 11-5919

Consumer Information

How It Works

Bottom Line: Aloe is safe for topical use. It is not an effective cancer treatment and is dangerous when given by injection.

Scientists think that compounds found in aloe inhibit molecules that play a role in inflammation. Studies in laboratory rats confirm this anti-inflammatory activity. Aloe is also thought to hinder the formation of thromboxane, a molecule that is detrimental to the healing of burn wounds. Aloe kills bacteria and fungi directly in laboratory studies. Aloe gel should not be confused with aloe juice or aloe latex, both of which contain potent laxative substances.

Purported Uses
  • As a topical anesthetic
    Laboratory evidence supports this use, but it has not been tested in clinical trials.
  • To treat burns
    Scientific evidence supports the topical use of aloe for minor burns.
  • To prevent and treat redness, rash, and pruritus caused by radiation therapy
    Clinical trials have produced conflicting results in support of and against this use. Topical use of aloe is generally safe.
  • As a skin moisturizer
    No scientific evidence supports this use.
  • To treat inflammation associated with conditions such as cold sores, eczema, and pruritis
    Clinical evidence supports this use.
  • To treat cancer
    No scientific evidence supports this use. Cancer therapy using injections of acemannan, a substance found in aloe, resulted in death of several patients.
  • To treat diabetes
    Two nonrandomized trials conducted by the same group suggest that blood glucose levels may be reduced by aloe vera. Further study is warranted.
  • To treat ulcerative colitis
    A small randomized, controlled trial shows weak support for this use. More research is needed.
Research Evidence

Side effects associated with Cancer treatments
A review of 131 studies involving 10,514 randomised participants was conducted to determine effectiveness of agents used to prevent oral mucositis in cancer patients. Ten interventions, where there was more than one study, showed some statistically significant evidence of benefit in preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. The treatments were aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate.
However, the strength of evidence varied and benefits may be specific for certain cancers and treatment. More well designed trials are needed to establish the above findings.

 

Patient Warnings
  • Aloe gel should not be confused with aloe juice or aloe latex, both of which contain anthraquinone, a potent laxative.
  • Despite the use of some oral dosages in clinical trials of ulcerative colitis, there is not enough evidence at this time to support the use of aloe vera by mouth or by injection. The risk of serious adverse effects is high, and several cancer patients died from aloe vera injections that were used as a cancer therapy.
Do Not Take If
  • If you are taking drugs that are substrates of Cytochrome P450 3A4 and CYP2D6: Aloe vera juice may increase the risk of side effects of these drugs.
  • If you are taking sevoflurane: Aloe may have additive antiplatelet effect causing excessive bleeding during surgery.
Side Effects
  • Certain dosages of aloe when taken orally, can cause GI upset, nausea, vomiting, and rash.
  • Toxicity from ingestion of aloe includes seizures, dangerously low blood potassium levels, and electrolyte abnormalities.
  • A case of hypokalemia (low potassium levels) has been reported with use of aloe vera during chemotherapy.
  • Three cases of toxic hepatitis (liver inflammation) were reported following use of aloe preparations. Liver function was normalized after discontinuing aloe.
E-mail your questions and comments to aboutherbs@mskcc.org.