Crocin Supplementation Significantly Reduces Chemotherapy-Induced Peripheral Neuropathy-Related Pain

by | Oct 12, 2022 | Botanicals, Cancer

Written by Taylor Woosley, Staff Writer. After 18 weeks of treatment, P/C arms showed a significant decrease in CIPN severity (P < 0.01) and an increase in patient’s recovery/improvement (P < 0.01) compared to C/P arms in all related scales. 

cancerCancer is one of the leading causes of death globally and the cancer burden has grown over time in both developed and developing countries1. Cancer therapy involves a multimodal strategy with a combination of chemotherapy, surgery, and radiotherapy2. Chemotherapeutic agents can damage nervous system structures and can cause a variety of neuropathies3. Chemotherapy-induced peripheral neuropathy (CIPN) can result in sensory, motor, and autonomic nerve damage and typically include paresthesia and pain4.

Saffron, dried stigmas of the plant Crocus sativus L., has been used in traditional medicine due to a variety of its main bioactive ingredients, most notably crocin5. Studies indicate various medicinal effects of crocin, such as providing anti-inflammatory and antioxidant properties6. Crocin is a water-soluble carotenoid that can affect certain cellular pathways and molecules because of their ability to bind to a wide range of proteins, including membrane proteins, mitochondrial proteins, structural proteins, and enzymes7. It has been shown that crocin increases glutathione synthesis and endogenous defense against oxidative stress8.

Borzogi et al. conducted a randomized, double-blind, placebo-controlled clinical trial to investigate the effects of crocin on CIPN. The study followed a crossover design consisting of two 8-week phases separated by a 2-week “washout” period. Study inclusion criteria were cancer patients with diagnosed neuropathy with symptomatic CIPN for at least a month duration with average daily symptom scores of 1) ≥4 on a 0-10 numerical rating scale 2) ≥1 on the 0–4 World Health Organization (WHO) score (0 = none; 1 = paresthesia/decreased tendon reflexes; 2 = severe paresthesia/ mild weakness; 3 = intolerable paresthesia/marked motor loss; 4 = paralysis); or 3) ≥1 on the 0–4 National Cancer Institute of Canada Common Toxicity Criteria (NCIC-CTC) or 4) ≥1 on the 0–4 Eastern Cooperative Oncology Group (ECOG) Neuropathy Scale.

Subjects were treated to either 15 mg crocin tablet (n=71) twice daily or were given an identical-appearing placebo tablet (n=66) at bedtime for 8 weeks. An aqueous saffron extract with crocin content of saffron measuring at 2.94 (~3) mg/15 mg of extract was created for the treatment group. After 8 weeks of treatment, participants stopped the treatment for a 2-week period and then the drug administration order between crocin and placebo were reversed. Primary outcomes included the severity of neuropathic complaints, as well as additional secondary efficacy measures. Secondary efficacy measures included: the Brief Pain Inventory (BPI) Short-Form which assesses the severity of pain and its influences on functioning, McGill Pain Questionnaire (MPQ) that measures both quality and intensity of subjective pain. Additionally, participants completed the Symptom Distress Scale (SDS), a 5-point scale to evaluate the construct of symptom distress and the Quality-of-Life Scale (QOLS).

Participants were monitored by weekly phone calls and questionnaires during the 8-week study period. Results of the randomized, double-blind, placebo-controlled clinical trial are as follows:

  • CIPN scores improved gradually for subjects in the crocin group, compared with their scores at baselines. Paired t-test results show a prominent and significant decrease in values at the end of the 8th week compared to the baseline scores in C/P arms (P < 0.01).
  • Mean scores at the end of the 18th week were significantly lower than the baselines at the end of the 10th week in P/C arms (P < 0.01).
  • At the end of the 8 weeks of therapy, symptom severity significantly decreased in C/P arms compared to P/C arms in all related scales. Changes in mean values in C/P arms compared to P/C arms were -2.5 (54.3%) by NRS average pain, -8 (33.3%) by NCIC-CTC scale, -0.04 (23.5%) by ENS scale, -0.8 (47%) by WHO scale, -0.4 (12.9%) by BPI scale, -8.3 (36.2%) by McGill pain rating index, -7.2 (10.8%) by SDS, and -0.9 (30%) by NPS.
  • Conversely, at the end of 18 weeks of therapy, P/C arms showed a significant decrease in CIPN severity (P < 0.01) and an increase in patient’s recovery/improvement (p < 0.01) compared to C/P arms in all related scales.

Significant findings of the study show that crocin has beneficial effects on CIPN and neuropathic pain in patients with chemotherapy injections. The CIPN-lowering effects of crocin were experienced during both sections of the trial in both C/P and P/C arms. Study limitations include not using a long-term intervention which might lead to better effects of crocin on measured parameters of neuropathy and the lack of evaluating the effect of crocin on biomarkers of inflammation and oxidative stress.

Source: Bozorgi, Hooman, Farahnaz Ghahremanfard, Ehsan Motaghi, Maryam Zamaemifard, Melika Zamani, and Amin Izadi. “Effectiveness of crocin of saffron (Crocus sativus L.) against chemotherapy-induced peripheral neuropathy: A randomized, double-blind, placebo-controlled clinical trial.” Journal of Ethnopharmacology 281 (2021): 114511.

© 2021 Elsevier B.V. All rights reserved.

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Posted October 12, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

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