Nicotinamide Riboside Helps Protect Nerve Fibers During Chemotherapy and Enhances Paclitaxel’s Tumor-suppressing Effects in Animal Models

Raising NAD+ levels with nicotinamide riboside has been shown, in animal models, to reduce pain resulting from the cancer treating drug therapy paclitaxel. When administered to rodents in combination with paclitaxel, NR also helped to further decrease tumor growth, suggesting NR may enhance the drug’s tumor-suppressing effects.

Chemotherapy: A Necessary Evil 

Chemotherapies are un-targeted, cytotoxic drugs that are used in the treatment of many cancers. While cancer cells are disproportionately killed because they are faster-replicating, other cells can also be harmed over the course of treatments, leading to many adverse side-effects. 

One such side-effect is chemotherapy-induced peripheral neuropathy (CIPN), which is pain in the extremities caused by damage to neurons. The American Society for Clinical Oncology considers the development of adjunctive therapy for the prevention and relief of CIPN as essential for patient care. 

Promisingly, a 2017 study in female rats found that Nicotinamide Riboside (NR) could relieve CIPN caused by the commonly used chemotherapeutic agent paclitaxel [1]. 

Paclitaxel works by over-stabilizing microtubules, a cellular component essential for the many cell divisions that cancers use to grow. Unfortunately, these microtubules are also indispensable for neurons, leading to dose-limiting pain in treated cancer patients [2]. 

In these rat models, the increase in NAD+ levels caused by NR helped improve the damage wrought by paclitaxel, potentially due to increased availability of cellular energy.  

Additional Animal Research Broadens Our Understanding

In 2020, an additional animal study investigated whether oral NR decreases the loss of intraepidermal fibers (IENF), bare nerve endings that enter the top layer of skin, caused by paclitaxel [3].

Study results showed NR reduced the loss of IENF in rats that both had, and did not have tumors. NR decreased tactile and sensory hypersensitivity caused by paclitaxel. Additional findings indicated that NR in combination with paclitaxel further decreased tumor growth, suggesting NR may enhance the drug’s tumor-suppressing effects. 

These findings are consistent with results from the 2017 study conducted by Donna Hammond, PhD and Marta Hamity, PhD, of the University of Iowa. Results add to existing preclinical evidence demonstrating NR may play a protective role following nerve injury and provides the foundational support needed to conduct future human clinical trials. 

Onward to Human Study

Dr. Hammond is now co-leading two teams running phase II clinical trials investigating the effect of NR in CIPN. The first clinical trial aims to determine whether NR prevents the progression of peripheral sensory neuropathy in patients receiving infusions of paclitaxel or nab-paclitaxel for the treatment of metastatic breast cancer or recurrent platinum-resistant ovarian, endometrial, peritoneal, or fallopian tube cancer [4]. The second clinical trial aims to determine whether NR can ameliorate persistent peripheral neuropathy in cancer survivors who have completed chemotherapy with taxane or platinum-complex compounds between 1 and 12 months earlier [5].

While further investigation is necessary to establish the role for NR in prevention of CIPN, the results from animal studies and initiation of clinical trials are a promising start. An effective means of mitigating CIPN could fundamentally improve the cancer treatment experience and enable longer, even safer chemotherapeutic approaches, leading to more effective results.

Footnote

All pre-clinical and clinical studies conducted used Niagen®, a form of nicotinamide riboside (NR) from ChromaDex.


References

  1. Hamity, M.V., et al., Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats. Pain, 2017. 158(5): p. 962-972. https://pubmed.ncbi.nlm.nih.gov/28346814/

  2. Weaver, B.A., How Taxol/paclitaxel kills cancer cells. Mol Biol Cell, 2014. 25(18): p. 2677-81. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161504/

  3. Hamity, M.V., et al., Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats. PAIN, 2020. 161(10). https://pubmed.ncbi.nlm.nih.gov/32433266/

  4. https://clinicaltrials.gov/ct2/show/NCT03642990

  5. https://clinicaltrials.gov/ct2/show/NCT04112641

Scientific AnalysisANAD Staff