Aloe vera | Cam-Cancer

Aloe vera

Abstract and key points

Aloe vera is a cactus-like plant and the gel from its leaves and juice are used for a wide range of problems. In oncology, Aloe vera is applied topically for radiation-induced skin problems, oral submucosal fibrosis (a precancerous condition) and chemotherapy-/radiation-induced inflammation of the digestive tract.

Supportive/palliative care

  • Radiation-induced skin problems: Two systematic reviews (n=7; n=4) and three additional randomized controlled trials (RCTs) have conflicting results and many limitations.
  • Radiation-induced oral mucositis: Although systematic reviews are inconclusive, moderate evidence from three RCTs suggests that Aloe vera mouthwash is as beneficial as conventional mouthwash in head and neck cancer and paediatric leukaemia and chemotherapy-induced stomatitis in leukaemia.
  • Radiation-induced proctitis: Evidence from two high-quality randomized clinical trials suggests that Aloe vera ointment may improve some symptoms compared to placebo.

Prevention

  • Oral submucosal fibrosis: Although topical Aloe vera has shown some positive results compared to conventional treatment, these findings are limited by the methodological limitations of the trials.

Antitumour treatment

  • Oral Aloe vera juice has been tested as an anti-cancer treatment, but studies are too preliminary to tell whether it is effective.

Numerous adverse events are on record but they are generally mild and reversible. Oral use might cause abortion.

Document history

Fully updated and revised in November 2020 by Ava Lorenc
Fully updated and revised in September 2018 by Ava Lorenc
Fully updated and revised in March 2013 by Edzard Ernst. 
Summary first published in July 2011, authored by Edzard Ernst.

Citation

Ava Lorenc, Edzard Ernst, CAM-Cancer Consortium. Aloe vera [online document], http://cam-cancer.org/en/aloe-vera. December 12, 2020.

What is it?

Description

Aloe vera or “true aloe” is the most widely known species of around 500 species of the Aloe genus. It is a cactus-like plant belonging to the Asphodelaceae family. Originally native to the Arabian Peninsula, it grows in tropical and subtropical climates growing and is widely cultivated around the world. For medicinal purposes Aloe gel produced in the inner part of the plant leaves and Aloe latex produced just under the plant’s skin are used. Aloe vera has a long history of medicinal use; today Aloe vera products are available over-the-counter and very popular, particularly for self-treatment and cosmetic use.

Other Aloe species include: Aloe barbadensis, Aloe vulgaris, Aloe chinensis, Aloe indica, Aloe littoralis,  Aloe lanzae.

Ingredients and quality requirements

Aloe vera gel is the mucilaginous tissue from the centre of the Aloe vera leaf and contains polysaccharides. Aloe vera latex (taken orally), is made of the peripheral bundle sheath cells and contains aloin, anthraquinones, barbaloine and glycosides (Ernst 2006).  The International Aloe Science Council (IASC) advises that Aloe vera products: have been checked for potential contaminants (pathogens, lactic acid, general APC, mould, yeast, heavy metals and undeclared maltodextrin); contain aloin A&B ≤10ppm for juice and powders; contain 1% total aloe solids in aloe vera leaf juice and 0.5% total aloe solids for inner leaf juice; contain minimal malic acid and glucose (IASC 2020).

Application and dosage

Gel is applied topically as needed. Latex is taken orally at doses between 50 and 200mg daily (Ernst 2006).

Alleged indications

Traditionally, Aloe vera has been used for a wide range of conditions. In oncology, the main claim is that topical application of the gel prevents or treats radiation-induced skin reactions (Ulbricht 2007). In the general population, Aloe vera is used by between 7 and 10% of adults in Australia, Italy, and Jamaica. In the USA, dietary supplements containing Aloe vera were used by 0.1% of adults in the past 30 days, and Aloe vera is the 20th best-selling dietary supplement, with sales of US$ 72million in 2011 (IARC 2016).

The notion that oral Aloe vera might prevent lung cancer was supported by a Japanese case-control study (Sakai 1989). A comparison of 44 pairs was analysed according to plant food intake. The results suggested that those study participants regularly consuming Aloe vera were associated with a reduced lung cancer-risk. Even though interesting, this small study cannot prove that the detected association is causal.

Mechanisms of action

A multitude of potential mechanisms of action has been identified by in vitro experiments (Ulbricht 2007). Aloe perryi flowers inhibit the growth of seven cancer cell lines (Al-Oqail 2016) and Aloe vera extract inhibits the growth of breast, cervical cancer and neuroblastoma cells, and increases the therapeutic efficacy of conventional drugs (Hussain 2015, Yonehara 2015). Regarding the constituents of Aloe vera, aloin/barbaloin exhibits anti-cancer effects through anti-angiogenic and cytotoxic activities (Cardenas 2006, Xiao 2007, Esmat 2006, Wang 2018, Li 2020), and aloe emodin inhibits the proliferation of cancer cells (including breast, pancreatic, prostate, colorectal, gastric, cervical, and lung cancers, glioma and melanoma (Wu 2018, Tabolacci 2015, Chihara 2015, Ismail 2013, Trybus 2018, Cheng 2018, Du 2019, Gao 2019, Hosseini 2020, Jiang 2020), induces the expression of genes involved in apoptosis (Haris 2014), induces cell differentiation (Tabolacci 2015), inhibits cancer metastasis (Ma 2016) and enhances the effect of radiation (Luo 2014), imatinib (Akev 2020) and tamoxifen (Tseng 2017). Photodynamic therapy with aloe-emodin causes cell death, induces autophagy, and inhibits adhesion, migration and invasion of cancer cells (Ismail 2013, Li 2016, Tu 2016, Chen 2018). Animal experiments have demonstrated detoxification of carcinogens (Singh 2000), reduced tumour angiogenesis (Kocik 2014, Arcella 2018) and reduction of papilloma growth in mice (Chaudhary 2007, Saini 2010) and chemopreventive effects (Chihara 2015, Im 2016,  Shimpo 2014, Birari 2020) through modulating antioxidant and detoxification enzyme activity (El-Shemy 2010, Wang 2020).

Aloe vera latex is a powerful laxative. Aloe vera gel has antimicrobial, antioxidant, antiproliferative, chemo-preventive, anti-inflammatory, moisturising and antipuritic actions (Ernst 2006, Richardson 2005, Su 2004). Anthraquinones of Aloe vera latex also have cytotoxic, radioprotective as well as anti angiogenic effects and inhibit angiogenic and metastatic regulatory processes (Lissoni 1998, Suboj 2012). In addition, aloin may enhance cisplatin antineoplastic activity in B16-F10 melanoma cells (Tabolacci 2013). Whole leaf extract of Aloe vera has been shown in animal experiments to have carcinogenic potential (Xiao 2007).

Aloin-loaded tablets may be a useful drug delivery system as a coadjuvant of conventional chemotherapy/radiation therapy (De Caro 2014).

Legal issues and cost

Aloe vera products are sold as cosmetics or as herbal supplements. High quality products are widely available and usually inexpensive. A typical week’s supply of Aloe vera gel would cost less than €6.

Does it work?

Four systematic reviews (Richardson 2005, de Almeida 2020, Yu 2020, Worthington 2011)  and 10 RCTs have investigated the use of Aloe vera for side effects of cancer radiotherapy treatment: skin problems (Rao 2017, Ahmadloo 2017, Sahebjamee 2015), oral mucositis (Puataweepong 2009, Sahebjamee 2015, Su 2004, Mansouri 2016, Alkhouli 2020), and proctitis (Sahebnasagh 2020, Sahebnasagh 2017). Four RCTs have investigated the use of Aloe vera for oral submucosal fibrosis (OSMF), a potentially malignant disorder of the oral mucosa (Sudarshan 2012, Patil 2014, Singh  2016, Anuradha 2016).

The results of the SRs and trials suggest:

Supportive/palliative care

  • Evidence for Aloe vera for radiation-induced skin problems is poor quality and conflicting.
  • Aloe vera may improve some symptoms of radiation-induced oral mucositis similarly to conventional mouthwashes, but this is based on only a few studies.
  • Evidence from two well conducted studies suggests that Aloe vera improves some symptoms of radiation-induced proctitis compared to placebo.

Antitumour treatment

  • Oral Aloe vera juice has been tested as an anti-cancer treatment, but the two studies are too preliminary to tell whether it is effective.

Prevention

  •  There is some moderate quality evidence (n=4) that Aloe vera may improve symptoms of oral submucosal fibrosis as well as conventional treatment.

Description of included studies

Supportive/palliative care

Radiation-induced skin problems

Richardson 2005 systematic review included seven randomized controlled trials (RCTs) of topical Aloe vera gel to treat radiation-induced skin problems. The quality of the studies and of reporting was frequently poor. Overall, the results failed to show the superiority of topical Aloe vera gel over various control treatments. The authors conclude that “there is no evidence from clinical trials to suggest that topical Aloe vera is effective in preventing or minimising radiation-induced skin reactions in cancer patients” (Richardson 2005).   De Almeida et al conducted a systematic review of medicinal plants for treating side effects of cancer treatment, including four studies of Aloe vera (de Almeida 2020). They found conflicting evidence from two studies on the effect of Aloe vera on skin reactions to radiotherapy.  Although the selection process seems thorough, this review may not have identified all relevant studies as they searched a small number of databases and used a limited range of keywords.

Three further trials of topical Aloe vera on radiation-induced skin problems were not included in either review (see evidence table for Aloe vera ) (Rao 2017, Sahebjamee 2015, Ahmadloo 2017). Topical Aloe vera may reduce the incidence of radiation-induced dermatitis in patients (n=60) with head and neck cancer (Rao 2017) although the study does have some limitations. One good quality (n=248) and one poor quality study (n=100) suggest no effect in breast cancer (Ahmadloo 2017, Hoopfer 2015).

Oral mucositis

A 2011 Cochrane review of interventions to prevent mucositis in cancer patients found “weak unreliable evidence that Aloe vera may be beneficial in the prevention of moderate to severe mucositis”, although this is now out of date (Worthington 2011).  The more recent systematic review (de Almeida 2020) included one small (n=26) and possibly underpowered but well conducted RCT (Sahebjamee 2015). It reports similar effects of Aloe vera on mucositis to those of benzydamine mouthwash. A 2020 systematic review and network meta-analysis of 9 oral care solutions for preventing oral mucositis ranked Aloe vera lowest out of the 9 interventions (Yu 2020), however this was based on the one small study by Sahebjamee 2015.

Two subsequently published RCTs studied Aloe vera for radiation-induced oral mucositis in head and neck cancer (see Table 1) (Su 2004, Puataweepong 2009), and two in patients with leukaemia - one with children (Alkhouli 2020), one for chemotherapy-induced stomatitis (Mansouri 2016).  There is moderate quality evidence that oral Aloe vera reduces the incidence but not duration of mucositis compared to placebo (n=61) (Puataweepong 2009), and may reduce onset, severity, intensity and pain better than or as well as conventional mouthwashes (n=26, n=64) (Mansouri 2016, Alkhouli 2020). However, Su 2004 (n=58) found no difference compared to placebo. Two of these studies had small sample sizes (Su 2004, Alkhouli 2020).

Proctitis

Two well conducted, powered and blinded RCTs investigated Aloe vera for proctitis in patients with pelvic cancer (n=42)(Sahebnasagh 2020); (n=20)(Sahebnasagh 2017). Both found that topical Aloe vera improves some symptoms of radiotherapy-induced proctitis (diarrhoea, faecal urgency, clinical presentation inflammation and lifestyle) and possibly rectal bleeding, compared to placebo (Sahebnasagh 2017, Sahebnagasgh 2020).

Antitumour treatment

There is preliminary evidence from two RCTs (n=240) that oral Aloe vera in combination with chemotherapy (n=240) (Lissoni 2009) or melatonin (n=50) (Lissoni 1998) may improve stabilization of disease and survival in patients with advanced solid tumours, for whom no other standard effective therapy is available.

Prevention

Oral Submucosal Fibrosis (OSMF)

Four trials tested Aloe vera for oral submucosal fibrosis (OSMF), three topical (gel) (n=20), (n=120), (n=40) (Sudarshan 2012, Patil 2014, Singh 2016) and one oral and topical (n=74) (Anuradha 2016) (see Table 1). OSMF is a potentially malignant disorder of the oral mucosa, frequently associated with chewing gutka and betel quid (Sudarshan 2012). There was some evidence that Aloe vera may improve symptoms (burning sensation, mouth opening, tongue protrusion and cheek flexibility) as well as conventional treatment, but all four trials have significant limitations in methodology and reporting

Is it safe?

Adverse effects

Numerous adverse effects are on record but, generally speaking, these are mild and reversible (Ulbricht 2007). Topical use: allergic reactions, delayed healing of deep wounds.

Oral use: irritation of and damage to intestinal mucosa, intestinal pain, vomiting, diarrhoea, cathartic colon, fluid and electrolyte loss, kidney failure, phototoxicity and hypersensitive reactions (Guo 2016).

Contraindications

Oral: pregnancy (oral administration can cause abortion), intestinal obstruction or inflammation.

Interactions

Oral: increased effects of antiarrhythmics, cardiac glycosides, diuretics and steroids (Ulbricht 2007).

Warning

Based on animal studies, there is a suspicion that oral use of Aloe vera might promote colonic cancer (Yokohira 2009, Bodreau 2013, Peng 2019, Peng 2020) although a subsequent study using Aloe vera extract with the latex component removed (which removed some mutagenic components (Guo 2014)) had no toxicological findings after 13 weeks (Sehgal 2013). There is also suspicion that topical use might enhance the induction of skin cancer by ultraviolet light (Photocarcinogenesis study of aloe vera).

Evidence tables
References

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Gao, R., X. Wu, Z. Huang, B. Wang, F. Li, H. Xu, and L. Ran. 2019. 'Anti-tumor effect of aloe-emodin on cervical cancer cells was associated with human papillomavirus E6/E7 and glucose metabolism', Onco Targets Ther, 12: 3713-21.

Guo X, Mei N. Aloe vera: A review of toxicity and adverse clinical effects. Journal of environmental science and health Part C, Environmental carcinogenesis & ecotoxicology reviews. 2016;34(2):77-96.

Guo X, Zhang S, Dial SL, Boudreau MD, Xia Q, Fu PP, et al. In vitro investigation of the mutagenic potential of Aloe vera extracts. Toxicology Research. 2014;3(6):487-96.

Haddad P, Amouzgar-Hashemi F, Samsami S, Chinichian S, Oghabian MA. Aloe vera for prevention of radiation-induced dermatitis: a self-controlled clinical trial. Current oncology (Toronto, Ont). 2013;20(4):e345-8.

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Jiang, X., Y. Liu, G. Zhang, S. Lin, J. Wu, X. Yan, Y. Ma, and M. Ma. 2020. 'Aloe-Emodin Induces Breast Tumor Cell Apoptosis through Upregulation of miR-15a/miR-16-1 That Suppresses BCL2', Evid Based Complement Alternat Med, 2020: 5108298.

Kocik J, Balan BJ, Zdanowski R, Jung L, Skopinska-Rozewska E, Skopinski P. Feeding mice with Aloe vera gel diminishes L-1 sarcoma-induced early neovascular response and tumor growth. Central-European journal of immunology. 2014;39(1):14-8.

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Ma JW, Hung CM, Lin YC, Ho CT, Kao JY, Way TD. Aloe-emodin inhibits HER-2 expression through the downregulation of Y-box binding protein-1 in HER-2-overexpressing human breast cancer cells. Oncotarget. 2016;7(37):58915-30.

Mansouri P, Haghighi M, Beheshtipour N, Ramzi M. The Effect of Aloe Vera Solution on Chemotherapy-Induced Stomatitis in Clients with Lymphoma and Leukemia: A Randomized Controlled Clinical Trial. International journal of community based nursing and midwifery. 2016;4(2):119-26.

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Peng, C., W. Zhang, C. Dai, W. Li, X. Shen, Y. Yuan, L. Yan, W. Zhang, and M. Yao. 2019. 'Study of the aqueous extract of Aloe vera and its two active components on the Wnt/beta-catenin and Notch signaling pathways in colorectal cancer cells', J Ethnopharmacol, 243: 112092.

Peng, C., W. Zhang, X. Shen, Y. Yuan, Y. Li, W. Zhang, and M. Yao. 2020. 'Post-transcriptional regulation activity through alternative splicing involved in the effects of Aloe vera on the Wnt/beta-catenin and Notch pathways in colorectal cancer cells', J Pharmacol Sci, 143: 148-55.

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Puataweepong P, Dhanachai M, Dangprasert S, Sithatani C, Sawangsilp T, Narkwong L, et al. The efficacy of oral Aloe vera juice for radiation induced mucositis in head and neck cancer patients: a double-blind placebo-controlled study. Asian Biomedicine. 2009;3(4):375-82.

Rao S, Hegde SK, Baliga-Rao MP, Palatty PL, George T, Baliga MS. An Aloe Vera-Based Cosmeceutical Cream Delays and Mitigates Ionizing Radiation-Induced Dermatitis in Head and Neck Cancer Patients Undergoing Curative Radiotherapy: A Clinical Study. Medicines (Basel, Switzerland). 2017;4(3).

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Sahebjamee M, Mansourian A, Hajimirzamohammad M, Mohammad H, Zadeh M, Bekhradi R, et al. Comparative Efficacy of Aloe vera and Benzydamine Mouthwashes on Radiation-induced Oral Mucositis: a Triple-blind, Randomised, Controlled Clinical Trial. Oral health & preventive dentistry. 2015; 13(4):309-15.

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Sahebnasagh, A., A. Ghasemi, J. Akbari, A. Alipour, H. Lashkardoost, S. Ala, S. J. Hosseinimehr, and E. Salehifar. 2020. 'Prevention of acute radiation-induced Proctitis by Aloe vera: a prospective randomized, double-blind, placebo controlled clinical trial in Pelvic Cancer patients', BMC Complement Med Ther, 20: 146.

Saini M, Goyal PK, Chaudhary G. Anti-tumor activity of Aloe vera against DMBA/croton oil-induced skin papillomagenesis in Swiss albino mice. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer. 2010;29(2):127-35.

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Shimpo K, Chihara T, Kaneko T, Beppu H, Wakamatsu K, Shinzato M, et al. Inhibitory effects of low-dose aloe-emodin on the development of colorectal tumors in min mice. Asian Pacific journal of cancer prevention : APJCP. 2014;15(14):5587-92.

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Su CK, Mehta V, Ravikumar L, Shah R, Pinto H, Halpern J, et al. Phase II double-blind randomized study comparing oral aloe vera versus placebo to prevent radiation-related mucositis in patients with head-and-neck neoplasms. International Journal of Radiation Oncology • Biology • Physics. 2004;60(1):171-7.

Suboj P, Babykutty S, Valiyaparambil Gopi DR, Nair RS, Srinivas P, Gopala S. Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-kappaB. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2012;45(5):581-91.

Sudarshan, R., R. G. Annigeri, and G. Sree Vijayabala. 2012. 'Aloe vera in the treatment for oral submucous fibrosis - a preliminary study', J Oral Pathol Med, 41: 755-61.

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