Is Functional Vitamin B12 Deficiency a Risk Factor for the Development of Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients?
Authors: EL-Najjar Samah E. , Naser Ihab A. , AL-Wahidi Kanan M. 
Published: September 2022

Background and aim:
Chemotherapy- induced peripheral neuropathy (CIPN) is a common, significant, debilitating symptom of anticancer treatment, continues to plague patients and the medical fraternity. CIPN interferes with optimal treatment of active disease resulting in the need for dose reduction, treatment delay and even premature cessation of chemotherapy and can severely affects the quality of life (QoL). Functional vitamin B12 deficiency, defined by elevated levels of vitamin B12- dependent metabolites, methylmalonic acid (MMA), and/or homocysteine, despite normal serum B12 values, may cause neuropathy and neuropathic pain. This study aimed to determine the role of functional vitamin B12 deficiency in the development of CIPN among cancer patients undergoing chemotherapy.
Methods
A prospective study design (short cohort study) was conducted to achieve the study objectives, utilizing non-probability purposive sampling technique. A consecutive case series of 64 adult (≥ 18 years) newly diagnosed cancer patients of various sites, registered and scheduled to receive the first cycle of chemotherapy were recruited from the Oncology Department of European Gaza Hospital (EGH). At two different points of time, at the baseline before the initiation of the first cycle of chemotherapy (pre) and after the completion of chemotherapy regimen (post), vitamin B12 status was evaluated using serum vitamin B12 and it is related metabolites methylmalonic acid (MMA) and homocysteine (Hcy), and CIPN was evaluated using patient neurotoxicity questionnaire (PNQ). The direction of association between CIPN and the indicator factors of functional vitamin B12 deficiency as well as other predicted variables was evaluated using stepwise multiple linear regression (MLR) analysis.
Results
Mean age of patients was 48.58 years. Males comprised 27(42.2%) of patients whereas female accounted for 37(57.8%). The results reported the presence of a functional vitamin B12 deficiency, such that there is a drastic reduction in serum vitamin B12 level (355.0(115.0) to 219.0(177.0) pg/ml, p < 0.001), accompanied by a significant increase in it is related metabolites MMA (3.9(3.0) to 49.7(32.0) ng/ml, p < 0.001) and Hcy (3.90(0.85) to 12.60(7.05) ng/ml, p < 0.001) after the completion of chemotherapy regimen.
The MLR model ensures a significant relationship between an MMA “the best sensitive indicator of functional vitamin B12 deficiency” and CIPN indicator, PNQ score significantly increased with increasing serum MMA level (b = 0.02, R2 = 0.30, p = 0.001). An increase of MMA by one significantly increases the CIPN indicator
score by 0.02 as b = 0.02. Furthermore, a one-point increase in the Subjective Global Assessment (SGA) increased the PNQ score by 0.31 (b = 0.31, R2 = 0.54, p = 0.004). Compared with non-diabetic patients, being a diabetic will increase the score of CIPN indicator by 0.38 (b = 0.38, R2 = 0.61, p = 0.032). A platinum compounds increase the CIPN indicator by 0.51 (b= 0.51, R2 = 0.79, p = 0.001). An increase in the patient age increased his/her PNQ score by 0.02 (b = 0.02, R2 = 0.83, p = 0.001). Moreover, the final model asserts that there is a significant association between the criterion variable (CIPN) and the two predictor variables (folate) and (vitamin B6), which were p = 0.012 and p = 0.039, respectively. A higher difference in folate (b = 0.15, 95% CI, 0.02,0.27) and vitamin B6 (b = 0.01, 95% CI, 0.0, 0.02) will be associated with an increase in the CIPN indicator score. Finally, the MLR results indicated that a consumption of three meals daily will lead to a decrease in CIPN indicator score by 1.07 (b = -1.07, R2= 0.74, p < 0.001).
Conclusion
Functional vitamin B12 deficiency is a distinct risk factor in the development of CIPN in cancer patients undergoing chemotherapy. This is clinically important, as early detection and treatment of functional vitamin B12 deficiency may prevent and/or alleviate CIPN symptoms. Further studies are required to evaluate the impact of vitamin B12 therapy in the management and/or prevention of CIPN.