B12 and nerves

Neuropathy is a broad term referring to damage to nerves anywhere in the nervous system. This can include damage to nerves in the central nervous system (brain and spinal cord) as well as the peripheral nervous system.The most common type is peripheral neuropathy, which affects nerves outside the brain and spinal cord, especially in the hands and feet. Longer nerves are particularly vulnerable to damage, and symptoms usually begin here.

B12 (cobalamin) plays an essential role as a coenzyme in many biochemical processes that maintain the function of the nervous system. It is especially critical for the DNA synthesis of oligodendrocytes, the cells that produce myelin, as well as the synthesis of myelin itself¹. The myelin sheath surrounds the axons of many nerves and acts as an electrical insulation, supporting fast and efficient nerve signaling. This role in myelin formation and remyelination includes the regeneration of nerves after an injury. 

B12 is also required for several other processes that support nervous system function, including the conversion of homocysteine to methionine, which can damage the nervous system by generating oxidative stress. B12 is also involved in the synthesis of fatty acids and nucleic acids, energy production, cell maturation and maintenance of the gastrointestinal mucosa.

B12 levels also affect the amount of glutathione in red blood cells and in the liver. Low glutathione and low B12 can increase oxidative stress in the body².

• Nutritional deficiencies
  B12 is required for regeneration and maintenance of the myelin sheath, while B1 facilitates the metabolism of carbohydrates for energy. B6 plays a key role in the metabolism of nerve cells and the synthesis of neurotransmitters. Deficiency in any of these nutrients can impair the repair and maintenance of nerves as well as the energy they need to function properly, contributing to nerve damage and degeneration.
  Neuropathy from vitamin B12 deficiency can occur even without typical signs of B12 deficiency, such as megaloblastic anemia and pancytopenia.^3,4
  
• Health conditions
  Diabetes mellitus, inflammatory conditions, autoimmune diseases, infections (eg, Lyme disease, hepatitis C), tumors and hypothyroidism have all been linked to nerve damage and neuropathy. B12 deficiency is common in patients with T2DM, and has been linked to several neurological disorders, including peripheral, autonomic (including cardiovascular) and painful neuropathy, which can accelerate the progression of diabetic neuropathy.
  Chronic alcoholism can damage the nerves due to the direct toxic effect of alcohol as well as malnutrition.
  
• Medications and toxins
  Medications such as chemotherapy agents, antibiotics and cardiovascular medications can affect nerve function. Antidiabetic medications such as metformin have also been linked to vitamin B12 insufficiency. Toxins from heavy metals, chemicals and pollutants may also have an impact.
  
• Physical damage
  Trauma or injury in which nerves are stretched, compressed, crushed or cut can impair nerve function.
  
• Age
  Oxidative stress, malnutrition and B12 deficiency is more common in older people, which can increase vulnerability of nerves.

Neuropathy resulting from B12 deficiency can include:

Peripheral neuropathy

• General fatigue and weakness
• Pain, numbness, tingling, ‘pins and needles’ sensation in the hands and feet
• Impaired motor function, including difficulty walking, muscle weakness and ataxia (reduced physical coordination)
• Optical neuropathy, including blurred vision or vision loss
• Cognitive dysfunction, such as memory loss, difficulty thinking and concentrating
• Mood changes, including depression or delusions

B12 is one of the most common treatments for neuropathy, and therapeutic doses of 1,000 mcg methylcobalamin per day have been shown to improve nerve symptoms and quality of life.

A 2021 systematic review concluded that there was ‘significant evidence’ for using B12 as part of a treatment plan for neuropathic pain. B12 was found to be particularly effective in treating post-herpetic neuralgia, alcohol-related neuropathy and diabetic neuropathy⁵.

A 2021 study found that 1,000 mcg methylcobalamin in a sublingual tablet per day for 12 months increased plasma B12 levels in patients with diabetic neuropathy and also improved all neurophysiological symptoms, reduced pain and improved quality of life⁶.

A 2015 study found that patients treated with 3mg methylfolate, 2 mg methylcobalamin and 35mg P5P experienced significant reduction in their symptoms as well as reduced pain⁷.

A 2022 study involving patients with fibromyalgia found that a short course of sublingual vitamin B12, 1,000 mcg daily, significantly improved the severity of fibromyalgia symptoms as well as the patient's anxiety⁸.

Nerve pain due to B12 deficiency is not usually one of the early symptoms. It may take some months or years to develop, depending on the severity of the deficiency and the cause.

Initial symptoms of B12 deficiency are usually linked to reduced red blood cell production and include fatigue, low mood, reduced concentration, shortness of breath and palpitations.

Untreated B12 deficiency may lead to damage or deterioration of the myelin sheath surrounding nerve fibres. This can then manifest as neurological symptoms such as numbness and tingling in the extremities and nerve pain. 

Vitamin B12’s role in regenerating myelin and supporting nerve health has made it a standard clinical treatment for nerve damage. Clinical trials show that supplementation with B12 improves axon growth of neuronal cells after peripheral nerve injury, promotes nerve cell survival and is directly involved in remyelination and the maintenance of myelin sheath⁹

B12 is thought to alleviate nerve pain via several mechanisms, including promoting myelination, increasing nerve regeneration and decreasing ectopic nerve firing. A 2020 systematic review found evidence for B12 as a drug treatment for neuropathic pain, particularly post-herpetic neuralgia and the treatment of painful peripheral neuropathy. 

In a study involving patients with traumatic brain injury, B12 improved nerve function by reducing stress-related apoptosis. It also restored microtubule stability and supported myelin repair, similar to the effects of 4-phenylbutyric acid (a medication for treating urea cycle disorders)¹⁰.

B12 is a neurotrophic substance with an affinity for neuronal tissues, and plays a central role in maintaining and regenerating peripheral nerves. By promoting the process of myelination, B12 supplementation is shown to lead to functional restoration. Numerous studies show that B12 supports healthy nerve regeneration and is directly involved in remyelination and the maintenance of myelin sheaths¹¹. It also appears to decrease ectopic nerve firing, which could explain why it helps alleviate painful symptoms¹²

Earlier studies show that high-dose vitamin B12 promotes neurite outgrowth and neuronal survival, as well as increasing extracellular signal-regulated kinases and Akt signaling after sciatic nerve injury. It also promoted functional recovery of nerves¹³

Vitamin B12 was found to promote functional recovery and axonal regeneration in patients with sciatic nerve injury, as well as attenuating edema and myelin sheath degeneration¹⁴.

A similar study found that B12 promoted functional recovery and histological regeneration of the injured sciatic nerve and its target muscle after sciatic nerve injury¹⁵.