From the Guidelines
Folic acid deficiency is not directly associated with peripheral neuropathy, but it can mask vitamin B12 deficiency, which is a known cause of peripheral neuropathy. Folic acid (vitamin B9) is essential for various bodily functions, including DNA synthesis and repair, as well as homocysteine metabolism 1. However, the relationship between folic acid deficiency and peripheral neuropathy is indirect, as folic acid supplementation can mask severe vitamin B12 depletion, which can lead to neurological symptoms, including peripheral neuropathy 1.
Key Points to Consider
- Folic acid deficiency may indicate non-adherence with daily multivitamin and mineral supplements or malabsorption, and some medications, such as anticonvulsants, sulfasalazine, and methotrexate, can affect folic acid levels 1.
- Treatment of folic acid deficiency involves oral folic acid 5 mg daily for a minimum of 4 months, but it is essential to exclude vitamin B12 deficiency before initiating treatment 1.
- Vitamin B12 deficiency, on the other hand, can cause peripheral neuropathy, and treatment involves hydroxocobalamin 1 mg intramuscularly, with the frequency of administration depending on the presence of neurological involvement 1.
Clinical Implications
- It is crucial to investigate and treat vitamin B12 deficiency promptly, especially in patients with possible neurological involvement, to prevent long-term damage to the nervous system 1.
- Folic acid supplementation should not be initiated without excluding vitamin B12 deficiency, as this can mask the symptoms of vitamin B12 deficiency and delay diagnosis and treatment 1.
From the Research
Folate Deficiency and Peripheral Neuropathy
- Folate deficiency may increase the risk of peripheral neuropathy, as suggested by a retrospective cohort study in the U.K. 2
- The study found that folate deficiency and insufficiency were associated with a greater risk of peripheral neuropathy among younger patients, with a hazard ratio of 1.83 for deficient folate levels and 1.48 for insufficient folate levels 2
- Another study investigated the role of folate deficiency in neuropathy caused by anticonvulsants and found that folate therapy significantly reversed abnormalities in motor and sensory nerve distal latencies 3
- A review of the neurology of folic acid deficiency noted that folate deficiency can cause peripheral neuropathy, although the exact mechanisms are not fully understood 4
- A study of clinicopathologic features of folate-deficiency neuropathy found that patients with folate deficiency showed a slowly progressive and sensory-dominant pattern of neuropathy, which was different from thiamine-deficiency neuropathy 5
Characteristics of Folate-Deficiency Neuropathy
- Folate-deficiency neuropathy is characterized by a slowly progressive and sensory-dominant pattern, with predominant involvement of the lower extremities 5
- The electrophysiologic features of folate-deficiency neuropathy are consistent with axonal neuropathy, and the histopathologic features indicate large fiber-predominant axonal loss without segmental demyelination 5
- Folate-deficiency neuropathy can be distinguished from thiamine-deficiency neuropathy by its slower progression, tendency to manifest as sensory neuropathy, and preservation of biceps tendon reflexes 5
Treatment and Prevention
- Folate therapy can reverse abnormalities in motor and sensory nerve distal latencies in patients with folate deficiency 3
- Folic acid supplementation can reduce serum homocysteine concentrations, which may be associated with a reduced risk of peripheral neuropathy 6
- However, folic acid supplementation has not been shown to have a beneficial effect on cognitive function or mood in healthy or cognitively impaired individuals 6