Black Mulberry Extract Shows Efficacy in Oral Mucositis Management for Patients Receiving Chemotherapy

Black mulberry extract was more effective than sodium bicarbonate in significantly decreasing oral mucositis and dry mouth symptoms in patients receiving chemotherapy, according to findings published in the Clinical Journal of Oncology Nursing.¹ Moreover, the intervention also yielded significant improvements in weight gain compared with controls.

In both the intervention (black mulberry extract) and control (sodium bicarbonate) group, there was a statistically significant decrease in mean scores in an oral assessment guide at 1-, 7-, and 15-days post-intervention (P = .001). According to the Oral Assessment Guide, the mean scores in the intervention group at days 1-, 7-, and 15- was 1.92 (standard deviation [SD], 0.45; range, 1-3), 1.53 (SD, 0.32; range 1-3), and 1.21 (SD, 0.21; range, 1-3). In the control group, the mean scores at the same follow-up intervals were 2.06 (SD, 0.38; range, 1-3), 1.9 (SD, 0.27; range, 1-3), and 1.77 (SD, 0.76; range, 1-3).

In the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) Late Radiation Morbidity Scoring Schema, the mean scores for dry mouth in the intervention group were 2.18 (SD, 0.5; range, 0-3), 1.31 (SD, 0.71; range, 0-2), and 0.54 (SD, 0.03; range, 0-1) and the mean scores in the control arm were 2.45 (SD, 0.75; range, 0-3), 2.05 (SD, 0.51; range 1-3), and 1.55 (SD, 0.51; range 1-2).

Investigators also determined that the weight gain in was significantly higher on days 7 and 15 among patients receiving the mulberry extract than among patients receiving the sodium bicarbonate. The mean scores in the experimental group, on days 7, and 15, were 65.3 (SD, 8.79), and 66.7 (SD, 7.98), and in the control group, were 68.47 (SD, 12.54), and 68.76 (SD, 12.51).

“Results from this study suggest that black mulberry extract may be effective in preventing or reducing mucositis for patients receiving chemotherapy and may also support weight gain," wrote Tuba Karabey, BSc, MSc, PhD, RN, assistant professor in the Faculty of Health Science at Tokat Gaziosmanpasa University and co-investigators, in the study.

“It is important to educate nurses and raise awareness about the use and importance of black mulberry extract in symptom management for patients with cancer [as] it is believed that recommending black mulberry extract to patients and their families for managing symptoms of oral mucositis and dry mouth, and continuing to apply it when they are discharged, can be effective in symptom control,” study authors added.

Chemotherapeutics agents—which suppress the growth and maturation of cells, disrupting the primary mucosal barrier in the mouth and throat—are often associated with oral mucositis. Oral mucositis can be linked to erythema, edema, bleeding, ulcerations, and hoarseness, as well as difficulty with breathing, chewing, and swallowing. It can also lead to inadequate nutrient intake, malnutrition, and communication problems, as of which can cause negative effects on a patient’s quality of life.

Black mulberry has been investigated in various settings as a management strategy for oral mucositis. The extract contains papiriflavonal A, kuraridin, saforaflavanon D, and saforaiso flavanon A—all of which have demonstrated antifungal and strong antimicrobial activity and are known to be effective in treating mouth and dental wounds. Black mulberry molasses demonstrated efficacy in decreasing oral mucositis in patient undergoing head and neck radiation, and black mulberry syrup reduced the toxicity in patients with obstructive pulmonary disease unrelated to cancer. However, Harman et al, found that black mulberry syrup did not prevent oral mucositis in patients undergoing stem cell transplantation,² and Sari et al, found that the syrup did not reduce the toxicity in patients receiving head and neck cancer radiation.³

The purpose of this study, therefore, was to assess the efficacy of black mulberry extract compared to sodium bicarbonate. In Turkey, where this study was conducted, sodium bicarbonate is one of the most common substances used to prevent mouth sores in patients undergoing chemotherapy (54.2%). Other common substances include chlorhexidine gluconate mouthwashes (68.2%); saltwater (51.7%); sage, chamomile, and fennel tea (46.7%); water with lemon (27.5%); black mulberry molasses (26.7%); honey (24.2%); and turmeric (17.5%).

A sample size of 40 patients were randomly assigned to either the sodium bicarbonate or black mulberry extract group. All patients were inpatients on the oncology unit, 18 years or older, and receiving their first course of treatment with methotrexate chemotherapy. The dose of methotrexate was 3.5 g/m²—the first 0.5 g/m² of which was administered in 1000 mL 0.9% sodium chloride over 15 minutes, and the remaining 3 g/m² was administered over 3 hours.

In the control group, nurse researchers applied 10 cc of 8.4% sodium bicarbonate mouthwash for 30 seconds 3 times daily for 15 days. In the intervention group, nurse researchers applied 5 ml of black mulberry extract for 60 seconds 3 times daily for 15 days. The extract contained ripe black mulberry fruit, citric acid, and about 9% fruit sugar. It did not contain glucose or preservatives. Patients were instructed not to consume anything within 15 to 20 minutes of extract application so as to not disturb the mucosal lining. Of note, the extract, which is approved by the Turkish Ministry of Agriculture and Rural Affairs, is not approved for the treatment of oral mucositis in the United States, but can be purchased by US residents through various online retailers, pharmacies, and grocery stores.

Based on the findings, study authors noted that nurses should educate patients about the potential benefits of complementary and nonpharmacologic treatments for symptom management, and to consider black mulberry extract in patients receiving chemotherapy.

Black mulberry extract represents a “cost-effective, evidence-based option to prevent oral mucositis caused by chemotherapy,” study authors concluded.

References

1. Karabey T, Karagözogli Ş, Aygün N, Sümer Z. The effect of oral care with black mulberry extract on oral mucositis, dry mouth, and weight gain in patients with cancer. Clin J Oncol Nurs. 2022;26(6):636-642. doi:10.1188/22.CJON.636-642
2. Harman M, Ovayolu N, Ovayolu O. The effect of three different solutions on preventing oral mucositis in cancer patients undergoing stem cell transplantation: a non-randomized controlled trial: a Turkish study - NON-RANDOMISED TRIAL. J Pak Med Assoc. 2019;69(6):811-816.
3. Yuce Sari S, Beduk Esen CS, Yazici G, Yuce D, Cengiz M, Ozyigit G. Do grape and black mulberry molasses have an effect on oral mucositis and quality of life in patients with head and neck cancer? Support Care Cancer. 2022;30(1):327-336. doi:10.1007/s00520-021-06411-6