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.
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.
Metabolic syndrome refers to a cluster of abnormalities such as hyperlipidemia, hyperglycemia, and obesity, and may lead to the development of diabetes and cardiovascular diseases. This condition is also associated with excess reactive oxygen species (ROS), and this redox imbalance is thought to correlate with further problems in metabolic syndrome. Artichoke (Cynara scolymus, Asteraceae) is consumed as a food and used medicinally for gastrointestinal problems. Artichoke leaf extract (ALE) has been shown to have beneficial effects for certain aspects of metabolic syndrome and is reported to have elevated antioxidant capacity. This double-blind, placebo-controlled, randomized, clinical trial investigated the potential effects of ALE intake on the oxidative stress and diet of patients with metabolic syndrome.
This study took place in Khoy, Iran, from November 2014 to May 2015. Metabolic syndrome was defined for this study as having 3 or more of the following: fasting blood sugar ≥ 100 mg/dL; triglyceride (TG) concentrations ≥ 150 mg/dL; blood pressure ≥ 130/85 mmHg; high-density lipoprotein cholesterol < 40 mg/dL for men or < 50 mg/dL for women; and waist circumference ≥ 95 cm (both men and women). Patients who wished to be in the study and were 20-50 years old were included. Those with systemic diseases such as diabetes, cancer, or Crohn’s disease, or those who, within the past 3 months, were consuming fish oil or antioxidant supplements, were taking pharmaceuticals for lipids or blood pressure or taking corticosteroids, were excluded. Also, those who smoked, were actively trying to lose weight, or had an allergy to artichoke, as well as women who were pregnant, lactating, or menopausal, were excluded.
The primary outcome of the study was any alteration in oxidative stress, with food consumption changes serving as the secondary outcome. The treatment and placebo were provided in tablet form by Dineh Pharmaceutical Company; Qazvin, Iran. ALE was prepared as a water-alcohol extract of leaves, standardized to contain 450 mg of a hydroalcoholic extract of artichoke leaf, with at least 4-5% chlorogenic acid. Placebo tablets contained corn (Zea mays, Poaceae) starch, lactose, and Avicel® (microcrystalline cellulose). Daily dosage was 4 tablets of either ALE (1,800 mg total) or placebo, with 1 tablet taken before breakfast and dinner, and 2 tablets taken before lunch. The total treatment duration was 12 weeks. Unused tablets served as a gauge of compliance. Patients were told not to alter their diet or exercise regimens and to report any adverse side effects.
Physical parameters (body mass index [BMI], weight, and waist circumference) and blood pressure were taken both at baseline and endpoint of the study. Physical activity was measured using the International Physical Activity Questionnaire, with results reported as high, moderate, and low, and dietary information was gathered using the software Nutritionist IV (First DataBank; San Bruno, California). Fasting blood was used for quantifying blood parameters; glutathione peroxidase and superoxide dismutase, both antioxidant enzymes, were measured in red blood cells, while total antioxidant capacity, TG, oxidized low-density lipoprotein (ox-LDL), and malondialdehyde concentrations, the latter both markers of oxidative stress, were measured in serum.
From 256 patients with metabolic syndrome, 80 were randomly assigned, with 40 patients in each group. In the ALE group, 7 patients were dropped from the study due to hypothyroidism or protocol violations, and 5 were dropped from the placebo group due to stopping the treatment or protocol violations; 33 patients in the ALE group and 35 in the placebo group finished the study. At baseline, no differences were seen between groups in any of the parameters, with 2 exceptions—in the placebo group, BMI was lower (P = 0.051) and diastolic blood pressure was significantly less (P = 0.030). Ox-LDL concentrations decreased significantly in those consuming ALE as compared with baseline (5,647.42 ± 1,031.93 ng/L vs. 5,914.28 ± 965.28 ng/L, P = 0.030). The decrease in ox-LDL across the study in the ALE group was also significantly greater as compared with that in the placebo group (−4.5% vs. −2.3%, P = 0.033). No other changes or differences in oxidative stress markers or enzymes were noted. No adverse side effects were observed.
The consumption of vitamin E and zinc significantly declined at the end of the study in the placebo group (P < 0.05 for both), and the amount of decrease in zinc consumption in the placebo group was significantly greater than that of the ALE group across the study (P = 0.019). In the ALE group, vitamin C consumption decreased, bordering significance (P = 0.061). Also, the percent decrease in TG concentrations was greater at the end of the study in the ALE group as compared with the placebo group (−17.74% vs. −5.02%, P = 0.010). No other parameters, including physical activity, were different from the study.
In conclusion, ALE consumption reduced ox-LDL as well as TG concentrations, indicating a potentially mild benefit to those with metabolic syndrome. As antioxidant status was unaffected in this study, oxidant status may have been acute or the oxidant stress too moderate to be detected. The authors suggest that the bioactivity observed may be due to compounds in ALE. There were some uneven physical parameters at baseline that may have influenced the outcomes reported here. Other discussed limitations include a short study duration and high amount of tablet consumption. Ideally, future studies will investigate the utility of ALE ingestion as an adjuvant for those with metabolic syndrome. The authors declare no conflict of interest.
Rezazadeh K, Aliashrafi S, Asghari-Jafarabadi M, Ebrahimi-Mameghani M. Antioxidant response to artichoke leaf extract supplementation in metabolic syndrome: a double-blind placebo-controlled randomized clinical trial. Clin Nutr. March 23, 2017; [epub ahead of print]. pii: S0261-5614(17)30108-5. doi: 10.1016/j.clnu.2017.03.017.