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Functional vitamin B12 deficiency in advanced malignancy: implications for the management of neuropathy and neuropathic pain

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Abstract

Background and aim

Treatment of neuropathic pain and chemotherapy-induced peripheral neuropathy (CIPN) in patients with malignancy is often unsuccessful. Functional vitamin B12 deficiency, defined by elevated levels of the B12-dependent metabolites, methylmalonic acid (MMA), and/or homocysteine, despite normal B12 values, may cause neuropathy and is associated with disorders linked to increased oxidative stress. Since both cancer and neurotoxic antineoplastic agents increase oxidative stress, a role for functional B12 deficiency in CIPN was considered.

Methods

A retrospective record review of 241 cancer subjects evaluated by the adult palliative care service for B12 deficiency in a university-based cancer center between October 2008 and September 2012 with measurement of B12, MMA, and/or homocysteine levels was performed.

Results

B12 values were elevated (>900 pg/ml) in 30 % and low (≤300 pg/ml) in 17 % of subjects tested. Elevated MMA (>250 nmol/l) and homocysteine (>12.1 μmol/l) levels occurred in 38 and 23 % of subjects respectively and at least one metabolite was increased in 54 % of evaluable subjects. Even when B12 values were ≥1500 pg/ml (n = 36), increased MMA and homocysteine values occurred in 31 and 23 % of subjects, respectively. B12 therapy decreased MMA values in all four subjects studied and improved neurologic findings in the three subjects tested.

Conclusions

Functional vitamin B12 deficiency is common in subjects with advanced malignancy. Further studies are needed to determine if this disorder is a risk factor for CIPN and if B12 therapy has a role in the management and/or prevention of neuropathy and neuropathic pain in this population.

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Acknowledgments

The author thanks D. Bonke (Merck, Darmstadt, Germany) for his suggestion regarding the possible effect of oxidative stress on cobalamin metabolism and R. Green (Department of Medical Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA) for his suggestion regarding the possible therapeutic role of methylcobalamin.

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  1. Section of Palliative Care, Department of Medicine, Yale University School of Medicine and Smilow Cancer Hospital, 333 Cedar Street WWW-403, P.O. Box 208021, New Haven, CT, 06520-8021, USA

    Lawrence R. Solomon

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Correspondence to Lawrence R. Solomon.

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Solomon, L.R. Functional vitamin B12 deficiency in advanced malignancy: implications for the management of neuropathy and neuropathic pain. Support Care Cancer 24, 3489–3494 (2016). https://doi.org/10.1007/s00520-016-3175-5

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