November 15, 2017

OPERA Supplementation for Chemotherapy-Induced Peripheral Neuropathy

Positive results, but how significant?
A small prospective study finds a combination of alpha lipoic acid, Boswellia serrata, methylsulfonylmethane, and bromelain improves symptoms in patients with chemotherapy-induced peripheral neuropathy.


This paper is part of NMJ's 2017 Oncology Special Issue. Read the paper or download the full issue here.


Desideri I, Francolini G, Becherini C, et al. Use of alpha lipoic, methylsulfonylmethane and bromelain dietary supplement (OPERA®) for chemotherapy-induced peripheral neuropathy management, a prospective study. Med Oncol. 2017;34(3):46.


To determine the efficacy and safety of OPERA® supplementation (240 mg alpha lipoic acid, 40 mg Boswellia serrata, 20 mg bromelain, and 200 mg methylsulfonylmethane [MSM]) in a series of patients with chemotherapy-induced peripheral neuropathy (CIPN).


Prospective intervention study


Twenty-five Caucasian adults with CIPN during or after chemotherapy with potentially neurotoxic agents; patients were enrolled in the study at the first clinical manifestation of neuropathy. The diagnosis of CIPN was based on the National Cancer Institute-Common Toxicity Criteria for Adverse Event (NCI-CTCAE) v4.0 grade of ≥1 for sensory neuropathy, with at least a report of paresthesia of fingers or toes (a criterion for grade 1).

Inclusion criteria were as follows: 18 years or older; Karnofsky performance score >70; treatment with one of the following agents: paclitaxel, docetaxel, nab-paclitaxel, oxaplatin, cisplatin, carboplatin, vinorelbine, vincristine, etoposide, eribulin mesylate; CIPN that evolved after or during standard chemotherapy. Twenty-three patients (92%) received chemotherapy with a neurotoxic agent at enrollment, while 2 patients (8%) had completed chemotherapy with a neurotoxic drug.


All patients were required to take an OPERA® capsule once a day, without regard to administration of food.

Study parameters assessed

Chemotherapy-induced peripheral neuropathy was assessed at the enrollment visit and repeated every 3 weeks until 12 weeks, using the following: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) v3.0, sensory and motor neuropathy score; the Total Neuropathy Score clinical version (TNSc); and the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory summary score (mISS). The Visual Analog Scale (VAS) for pain was used to assess pain intensity.

Primary outcome measures

Primary endpoint was the evaluation of changes of measured scores after 12 weeks of therapy compared to baseline evaluation. Secondary endpoints were the evaluation of neuropathy reduction at 12 weeks after beginning of therapy with OPERA®.

Key findings

OPERA® dietary supplement was able to improve CIPN symptoms in a prospective case series of patients treated with neurotoxic chemotherapy, with no significant toxicity or interaction. In addition, no worsening of pain or CIPN symptoms was reported with use of OPERA®. There was no statistical analysis performed for this study.

Practice implications

Chemotherapy-induced peripheral neuropathy describes damage to the peripheral nervous system incurred by a patient who has received a neurotoxic chemotherapeutic agent. It is a frequent dose-limiting side effect for cancer patients treated with platinum-derived compounds, vinca alkaloids, taxanes, and the proteasome inhibitors.1 Neurotoxicity incidence varies depending on the agent used and cumulative dose, with rates ranging from 19% to more than 85% in patients treated with multiple agents.2 A recent meta-analysis showed a CIPN prevalence of 68.1% (95% CI: 57.7-78.4) within the first month post-chemotherapy, 60.0% at 3 months, and 30.0% at 6 months or later.3

No reliably effective treatment has been established to prevent or treat CIPN symptoms. Duloxetine has provided only modest benefit and has associated side effects and a high dropout rate. The 2014 American Society of Clinical Oncology CIPN guideline gives a moderate recommendation for treatment with duloxetin, and recommends further research in this area.4 New safe and effective treatments are needed.

Increased interest in CIPN has included the investigation of several nonpharmaceutical interventions. This study evaluates the dietary supplement OPERA® to treat CIPN. While the authors established the efficacy and safety of OPERA® for CIPN, there are several restrictive variables. There is limited and conflicting evidence for the components of OPERA®. Alpha-lipoic acid has been shown to boost levels of glutathione and support healthy nerve tissue and blood sugar levels.5 Boswellia serrata is a potent anti-inflammatory herb and helps to balance the activity of 5-lipoxygenase (LOX) and support a healthy inflammatory response.6 Methylsulfonylmethane has been shown to reduce C-fiber nerve conduction,7 which is essential for effective pain control. It also has chemopreventive properties and anti-inflammatory activities.8,9

No reliably effective treatment has been established to prevent or treat CIPN symptoms.

The components of OPERA® may work synergistically to improve the symptoms of CIPN because they collectively have anti-inflammatory effects, potent antioxidant properties, and potential benefit for diabetic neuropathy (nerve health and blood sugar control); however, evidence is lacking for the effectiveness of these constituents individually for the use of CIPN. A clear limitation of this study is its small sample size and nonhomogeneous patient population. Despite these limitations, the authors claim that OPERA® reduced patients’ perception of pain, improved motor and sensory impairments, and was well-tolerated, with no treatment-related toxicities. Unfortunately, the authors failed to statistically analyze their results. Lack of statistical significance makes these seemingly positive outcomes impossible to interpret.

While the authors of this study report that OPERA® was safe and effective, these results are not significant given the lack of statistical analysis. The activity of this dietary supplement may benefit patients with CIPN, but future well-designed, prospective, randomized controlled trials are warranted to support its use in these patients.

Categorized Under


  1. Quasthoff S, Hartung HP. Chemotherapy-induced peripheral neuropathy. J Neurol. 2002;249(1):9-17.
  2. Fallon MT. Neuropathic pain in cancer. Br J Anaesth. 2013;111(1):105-111.
  3. Seretny M, Currie G, Sena E, et al. Incidence, prevalence, and predictors, of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain. 2014;155(12):2461-2470.
  4. Hershman D, Lachetti C, Dworkin R, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32(18):1941-1967.
  5. Vallianou N, Evangelopoulous A, Koutalas P. Alpha-lipoic acid and diabetic neuropathy. Rev Diabet Stud. 2009;6(4):230-236.
  6. Ammon HP. Boswellic acids in chronic inflammatory diseases. Planta Med. 2006;72(12):1100-1116.
  7. Jimenez R, Wilkens R. Dimethylsulfoxide: a perspective of its use in rheumatic diseases. J Lab Clin Med. 1982:100(4):489-500.
  8. Ebisuzaki K. Aspirin and methylsulfonylmethane (MSM): a search for common mechanisms, with implications for cancer prevention. Anticancer Res. 2003;23(1A):453-458.
  9. Debbi EM, Agar G, Fichman G, et al. Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study. BMC Complement Altern Med. 2011;11:50.