Aloe Vera Cream Delays Development of Radiation-induced Dermatitis in Patients with Head and Neck Cancers

Treatments for head and neck cancers include surgery, chemotherapy, and radiotherapy, used either alone or in combination. Used to treat inoperable tumors, radiotherapy can cause radiation-induced dermatitis, which is treated with steroidal, nonsteroidal, and metallic topical medications. Researchers have studied the use of skin care products containing aloe vera (Aloe vera, Asphodelaceae) in patients undergoing radiotherapy. Aloe vera has been shown to have anti-inflammatory properties and researched for its use in treating a variety of skin ailments including eczema, psoriasis, burns, wounds, and ultraviolet (UV)-induced skin erythema. These authors conducted a single-center, investigator-blinded, randomized, clinical study to evaluate the efficacy of a topical aloe vera-based cream (AVC) in preventing radiation-induced dermatitis in patients undergoing therapeutic radiation for head and neck cancers.

The study was conducted between July 2012 and December 2012 in the Department of Radiation Oncology at Mangalore Institute of Oncology in Pumpwell, Mangalore, India. Eligible patients were those scheduled to receive radiotherapy or chemoradiotherapy 6 weeks following surgery and who had a Karnofsky Performance Status Scale score above 70, meaning that patients could care for themselves but could not carry on normal activity or do active work.

Sixty patients were randomly assigned, with 30 in each group, to either the Johnson’s® Baby Oil (JBO) (Johnson & Johnson; Mumbai, India) control group or the AVC Elovera® (Glenmark; Mumbai, India) group. Elovera consists primarily of 10% aloe vera extract and 0.5% vitamin E. At baseline, the mean age for the JBO group was 55.2 ± 9.66 years, and for the AVC group, 55.9 ± 8.99 years. Males represented 24 patients in the JBO group and 26 in the AVC group. During the second week of treatment, 1 patient in the JBO group died of cancer.

All patients received irradiation at a maximum energy level of 6 MV at a rate of 300 MU per minute. All fields were treated 5 days a week with no more than 1 fraction of 2 Gy daily. Patients scheduled for chemoradiotherapy received carboplatin infusions weekly 3 hours before the first weekly radiation treatment. Before starting the study, the patients and their caregivers were taught how to apply the JBO (5 mL) or AVC (5 g) 5 times daily as follows: 2 hours before, immediately after, and 2, 4, and 6 hours after radiotherapy. Use of JBO or AVC was discontinued if moist desquamation occurred, and 1% gentian violet paint was applied instead.

The patients were assessed for radiation-induced dermatitis weekly according to the criteria of the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer, which ranks skin condition as follows: grade 0 (no skin rending, ulceration, inflammation, or damage); grade 1 (faint erythema or dry desquamation); grade 2 (moderate to brisk erythema, patchy moist desquamation mostly confined to skin folds and creases, moderate edema); grade 3 (moist desquamation ≤1.5 cm in diameter in areas other than skin folds or creases, and bleeding induced by minor trauma or abrasion); and grade 4 (skin necrosis or ulceration of full-thickness dermis and spontaneous bleeding from the involved site).

After weeks 1 and 2, patients in both groups had normal skin, without any signs of radiation-induced dermatitis. Following week 2, dermatitis was observed in the 2 groups as follows:

  • Week 3: 41.4% in the JBO group and 16.7% in the AVC group
  • Week 4: 82.8% in the JBO group and 70% in the AVC group
  • Week 5: 93.1% in the JBO group and 90% in the AVC group
  • Weeks 6 and 7: 96.6% in the JBO group and 90% in the AVC group
  • Two weeks post-treatment: 86.2% in the JBO group and 73.3% in the AVC group

Dermatitis reported in both groups at week 3 was grade 1; the between-group difference in the incidence was significant (P=0.04). After week 4, grade 2 dermatitis was seen in both groups. The most severe dermatitis of grade 3 was reported by 34.48% in the JBO group and 40% in the AVC group at week 7 (P=0.07). No one developed grade 4 dermatitis. Two weeks post-treatment, the average grade of dermatitis was lower in the AVC group compared with the JBO group; specifically, the patients in the AVC group had a significantly lower incidence of grade 2 dermatitis compared with the JBO group (P<0.02).

Earlier studies reported that aloe vera gel, used with mild soap, relieved dermatitis in women undergoing radiation for breast cancer1; “[h]owever,” write the authors of the study reported here, “the observation that an Aloe vera-based cream delays the incidence of dermatitis (when evaluated from the initiation of the treatment) is novel and indicates the usefulness of Aloe vera in enhancing the healing of radiation dermatitis.” Other studies have shown that aloe vera enhances wound healing.2,3

The authors conclude that the prophylactic use of an AVC delays the development of radiation-induced dermatitis in patients being treated for head and neck cancers. Further studies with a larger sample size are needed to further validate the efficacy of aloe vera.

References

1Ryan JL. Ionizing radiation: the good, the bad, and the ugly. J Invest Dermatol. 2012;132(3 Pt 2):985-993.

2Atiba A, Nishimura M, Kakinuma S, et al. Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-β and fibroblast growth factor production. Am J Surg. 2011;201(6):809-818.

3Visuthikosol V, Chowchuen B, Sukwanarat Y, Sriurairatana S, Boonpucknavig V. Effect of Aloe vera gel to healing of burn wound: a clinical and histologic study. J Med Assoc Thai. 1995;78(8):403-409. 

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). June 2017:4(3):44. doi: 10.3390/medicines4030044.

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Review on the Effectiveness of Aloe Vera for Oral Diseases

The succulent leaves of the aloe vera (Aloe vera, Xanthorrhoeaceae) plant have been used medicinally for hundreds of years. The clear gel, or mucilage, found inside the leaves, is well known for having wound-healing, anti-inflammatory, antioxidant, antitumor, and analgesic properties. These attributes could potentially help in treating oral ailments. The aim of this systematic review was to accumulate and assess clinical trials evaluating the effectiveness of aloe vera preparations in treating various oral diseases.

Studies on aloe vera were eligible if they were randomized, controlled, single- or double-blind, cross-sectional, or case-controlled trials published as full papers in English. PubMed (Medline), Scopus, Cochrane Database, Embase, and ScienceDirect were searched from July 1998 to December 2015. Search terms included “herbs,” “Ayurveda,” and “oral mucosa.” The Jadad scale (a scale ranging from 0 to 5, where the higher number indicates higher trial quality) was used to assess quality.

In total, 15 articles met the inclusion criteria. Only six trials achieved a Jadad score of 4/5; the rest scored between 0 and 3. Most studies were carried out in hospital clinics in countries such as Iran, Spain, India, the United States, and Saudi Arabia. Study populations ranged from 20 to 110 patients with clinically diagnosed oral mucosal lesions. Five of the 15 studies focused on patients with oral lichen planus (OLP). Two studies examined efficacy on oral submucous fibrosis (OSMF) in patients. The remaining studies investigated the effects of aloe vera on burning mouth syndrome, radiation-induced mucositis, Candida-associated denture stomatitis, xerostomia, and minor recurrent aphthous/stomatitis. All studies demonstrated a low risk of bias using the Cochrane Risk of Bias Tool. Blinding bias was low among all studies except one on Candida-associated denture stomatitis. Randomization sequence bias was high in seven studies.

Most studies showed statistically significant results for efficacy of aloe vera in treatment of oral lesions. There were no withdrawals due to adverse effects of aloe vera in any of the clinical trials. This review found aloe vera was most beneficial in patients with OLP. All five studies in patients with OLP demonstrated a low risk of bias and proved aloe vera effectively reduced lesion-associated pain and burning sensation, leading to partial or complete remission of symptoms. Studies conducted in patients with OSMF showed aloe vera to be effective in all stages of OSMF, particularly mild-stage OSMF clinically and early-stage OSMF histopathologically. Pain and burning sensations were significantly reduced in OSMF studies, and other outcome measures (mouth opening, cheek flexibility, tongue protrusion) were promising. The overall quality of OSMF studies was good with low risk of bias. Four trials in patients with aphthous stomatitis were reviewed, consisting of 319 patients. The overall quality of these studies was good. Lesion healing improved and there was significant remission of pain, erythema, and lesion size. Aloe vera was found to be less beneficial in patients with radiation-induced mucositis, as it was not effective in improving tolerance to head and neck radiotherapy, decreasing mucositis, or decreasing soreness; however, quality-of-life measures were improved in the patients receiving aloe vera. In the single Candida study reviewed, aloe vera had an anticandidal oral effect surpassed by that of Triphala, an Ayurvedic combination remedy.

Lack of randomization, lack of double-blinding, and a lack of description for withdrawals, dropouts, and methods to generate the sequence of randomization were all prevalent limitations that excluded trials from this review. The studies included demonstrated aloe vera has a wide spectrum of properties and uses and is a promising agent in treating oral lesions. However, based on this review, aloe vera may be better suited to OLP, OSMF, and aphthous stomatitis lesions versus those induced by radiation or Candida. For aloe vera to be more seriously considered for clinical treatment of oral lesions, future clinical trials should strive to meet more rigorous standards.

Resource:

Nair GR, Naidu GS, Jain S, Nagi R, Makkad RS, Jha A. Clinical effectiveness of aloe vera in the management of oral mucosal diseases – A systematic review. J Clin Diagn Res. August 1, 2016;10(8): ZE01-ZE07. doi: 10.7860/JCDR/2016/18142.8222.

 

Climate Effects on Phytochemistry and Antioxidant Activity of Aloe Vera

Aloe vera (Aloe vera, Xanthorrhoeaceae), a perennial succulent native to South Africa, thrives in subtropical and tropical regions. It is drought-resistant and tolerates a wide range of climatic conditions. Aloe vera is a rich source of phytochemicals, some of which have been shown to have anti-inflammatory, antibacterial, antioxidant, immune-boosting, anticancer, anti-aging, and antidiabetic effects. Medicinally, it is used for burns, eczema, inflammation, and fever. Potent antioxidants such as barbendol, emodin, barbaloin A, and chrysene have been isolated from methanolic extracts of aloe vera as putative bioactive. However, its overall effects may be due to synergistic effects of these and other constituents.

To investigate effects of agro-climatic zones on phytochemical content of different populations of aloe vera in India, the authors harvested fresh leaves from 12 collection areas in six climatic zones, prepared methanolic extracts from them, and assayed their antioxidant capacity. Total phenolic content (TPC) of extracts was determined spectrometrically using the Folin-Ciocalteu method, with gallic acid as the standard and results expressed as mg gallic acid equivalent (GAE)/g of extract. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, hydrogen peroxide (H2O2) scavenging, reducing power, metal chelating, and β-carotene-linoleic acid assays were performed on each extract in triplicate and mean values of results calculated. Preparation of extracts and each assay is described.

In qualitative phytochemical screening, aloe vera methanolic extracts showed the presence of alkaloids, glycosides, reducing sugars, phenolic compounds, steroids and terpenoids, flavonoids, tannins, and saponin glycosides. All antioxidant assays showed significant antioxidant activity ranging from 56-80%. Extracts from different agro-climatic zones differed significantly in antioxidant potential. For example, in the DPPH scavenging assay, Punjab (semi-arid), Himachal Pradesh (highland), and Haryana (semi-arid) accessions had the highest antioxidant capacity at 75.54-80.2%. Accessions from Telangana (tropical wet and dry), Gujarat (arid), and West Bengal (tropical wet and dry) had the least antioxidant capacity at 56.75-62.66%. By comparison, ascorbic acid had 96% radical scavenging ability. In the H2O2 scavenging assay, where ascorbic acid as the standard had reducing the activity of 97%, aloe vera extracts from Punjab, Telangana, and Himachal Pradesh had the highest activity, while that from West Bengal had the least. Strong correlations were observed between TPC and antioxidant activity.

Phytochemical composition of plants is influenced by environmental factors including geography, climate, soil type, sun exposure, grazing stress, seasonal changes, and more. Studies of plants in stressful situations show greater production of flavonoids, anthocyanins, and mucilaginous substances. An increase in unsaturated fatty acid production has been associated with cooler climates. In the case of aloe vera, previous findings on antibacterial activity on the same extracts as in the present study also support these statements. Aloe vera plants from hilly areas are traditionally more valued for nutritional use. In this study, accessions from colder regions in northern India had more antioxidant potential than those from hotter regions in southern India. Effects of soil conditions and other factors, including climate change effect, in these regions remain to be evaluated.

This study demonstrates that aloe vera is a promising source of bioactive phenolic compounds with good antioxidant capacity and that antioxidant capacity is higher in plants grown in northern India. However, without further identification of specific phytochemicals and biological testing, it is hard to suggest which combination of qualitatively determined phytochemicals is the most relevant for biological activity in humans. Further research should include in vivo studies of the extracts and individual constituents for inflammation and related conditions. The study may or may not guide some aloe vera cultivators to grow the plant in cooler areas for stronger antioxidant capacity; others may choose hotter climes to obtain more overall plant mass.

Regarding climate change, this must be seen as a baseline study. Plants were not subjected to documented climate change in this study but harvested one time from different climatic zones. While the authors state that India’s climate, largely controlled by an annual monsoon, “appears to be experiencing increasingly severe and erratic precipitation,” only an average rainfall is shown for each collection site, with no evidence of change. Nor is any effect of rainfall on TPC or antioxidant capacity discussed, only relative coolness and heat. If the study is repeated in five years and correlated with then-available evidence of climate change in India, it may or may not show divergence from the baseline data established by these authors. Caution is warranted regarding the study’s results as the information garnered is a very basic qualitative phytochemical screen and bioassays that have not been shown to have a direct biological correlation in vivo.

Resource:

Kumar S, Yadav A, Yadav M, Yadav JP. Effect of climate change on phytochemical diversity, total phenolic content and in vitro antioxidant activity of Aloe vera (L.) Burm.f. BMC Res Notes. January 25, 2017;10(1):60. doi: 10.1186/s13104-017-2385-3.