New insights into the pathophysiology of cobalamin deficiency

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

“…These include mitochondrial L-methymalonyl-coenzyme A (CoA) mutase and cytoplasmic homocysteine methyl transferase (also known as methionine synthase) [163,164]. Reduced activities of these two enzymes alone have been linked to the neurological manifestations of a vitamin B12…”

“…Scalabrino, et al [163] reported that the severity of the neuropathological features of white matter in the spinal cord of totally gastrectomised rats does not correlate with the progressive accumulation of methylmalonylic acid (MMA) and homocysteine (HCY) in the serum or the spinal cord [162]. The authors hypothesised that the accumulation of these neurotoxic metabolites from chronic cobalamin deficiency was unlikely to be the main mechanism of action to cause the subacute combined degeneration like lesions.…”

“…Research into the mechanisms of action of these nerves has revealed that nerve damage from a vitamin B12 deficiency may be via its effect on glial cells (Schwann cells are the peripheral nerve glia cells) as well as the impact of certain cytokines and growth factors [163]. Nerve cells such as the glial cells synthesise and release certain cytokines and growth factors due to injury or following certain triggers.…”

“…Nerve cells such as the glial cells synthesise and release certain cytokines and growth factors due to injury or following certain triggers. This neuroglial pattern of cytokine and growth factor production can lead to demyelination and phlogosis from cytokines such as tumour necrosis factor alpha (TNF-α) [163].…”

“…It was concluded that this imbalance of TNF-α and EGF can cause demyelination leading to nerve damage from a vitamin B12 deficiency [163]. Figure 1-10 represents a vitamin B12 deficiency in adults due to an imbalance of TNF-α and EGF [163].…”