High-dose B vitamins effective for management of neuropathy

Recent evidence continues to affirm the effectiveness of high-dose B vitamins in the management of neuropathy. Dr Joseph Lam, Specialist in Neurosurgery in Hong Kong, discussed the role of B vitamins in neuropathic pain management and shared his experience on the use of vitamins B1, B6 and B12 fixed-dose combination (FDC) preparations such as Neurobion (Merck) in clinical practice.


Neuropathic pain management

“Neuropathy, the most common secondary complication associated with diabetes mellitus, is expected to develop in up to half of all diabetic patients. An estimated 11.5 percent of the Hong Kong population has neuropathy, excluding those with mixed neuropathic and nociceptive pain conditions,” highlighted Lam.


“Combination treatment addressing both the nociceptive and neuropathic components would be a rational approach in the absence of standard treatment guidelines”


“Early detection of neuropathy in primary and specialty care settings is crucial to avoid unnecessary delays in treatment,” he noted. “When more than 50 percent of nerve fibres are lost, the damage is irreversible.”


“However, diagnosing neuropathy is difficult as the pain is often caused by mixed pathophysiology. Further more, symptoms of nociceptive and neuropathic pain may overlap, and patients may have difficulty describing them despite the availability of tools such as comprehensive questionnaires,” he explained. “The clinical utility for the Chinese version of the painDETECT questionnaire, which will hopefully improve the differential diagnosis of different types of pain, is currently being evaluated.”


“As such, combination treatment addressing both the nociceptive and neuropathic components would be a rational approach in the absence of standard treatment guidelines,” said Lam. [Curr Med Res Opin 2011;27:11-33; Pain Research and Treatment Vol 2012, Article ID 154781, doi:10.1155/2012/154781]


The B vitamins

“Vitamins B1, [thiamine],B6 [cobalamin], have demonstrated efficacy in significantly relieving neuropathic symptoms such as pain, burning sensations, tingling and numbness. They haver been part of the therapeutic armamentarium comprising tricyclic antidepressants, opioids, NSAIDS and novel agents such as pregabalin and gabapentin in the management of chronic pain,” noted Lam. [Diabetes Obes Metab 200810:99-108 Nutr Rev 200;62:96-104]


“Preclinical studies have suggested that B vitamins contribute to nerve health and neuropathic pain control via different biochemical mechanisms. Vitamin B1 is essential in neuronal physiology and neurotransmitter metabolism, and has a synaptic membrane stabilizing effect. Vitamin B6 is needed in the synthesis of neurotransmitters and is therefore vital for nerve function, while vitamin B12 has nerve function restoration roles, being key in the formation of nerve myelin sheaths, remyelination and nerve regeneration,” he said. [N Engl J Med 2013;368:2041-2042;Rev 2004;62:96-104; Acta Diabetol 2008; 45:131-141]


“Adequate absorption may be achieved with high doses of oral vitamin B12 to produce therapeutic serum levels”


Intramuscular injection of high dose (1,000) vitamin B12 has been found to be safe and efficacious in alleviating low back pain and related disability in a randomized, double blind, placebo-controlled study in 60 patients with lumbago or sciatic neuritis with no sign of nutritional deficiency. The treatment was also associated with decreased use of paracetamol in the patients. [Eur Rev Med Pharmacol Sci ;4:53-58]


"Vitamin B12, traditionally administered intramuscularly, is found to be equally effective when administered orally as it is absorbed both actively and passively. Passive diffusion accounts for 1-2 percent of total vitamin B12 absorption. As such, adequate absorption may be achieved with high doses of oral vitamin B12, thus allowing oral vitamin B12 to be an alternative or replacement for intramuscular vitamin B 12,” said Lam. [Drug Res 1997;47:369-380; Fam Pract 2006;23:279-285]


Fixed-dose combinations

"As these three B vitamins have different roles in neurotransmission and in counteracting nerve damage, we usually give a FDC of these three components,” said Lam. “Such FDC combinations are safe for long-term use. Very high does of vitamins B1 and B12 [current US FDA-approved dose for vitamin B12 is 5,000/day] can be safely given without side effects. However, the vitamin B6 dose should not exceed 1 g/day for more than 2 months due to the risk of neurotoxic side effects,” Lam pointed out.


A FDC of vitamins B1, B6 and B12 resembling Neurobion injection has demonstrated superiority vs each B vitamin alone in ameliorating allodynia, formalin-evoked hyperalgesia and nerve conduction velocity slowing in diabetic rats, suggesting a potential for use as an inexpensive and safe long-term treatment for diabetic neuropathy. (Figure1)[Eur J Pharmacol 2009;612:41-47]


In a case-series study in 43 patients with diabetic peripheral neuropathy, oral treatment with a similar combination of vitamins B1 (100 mg), B6 (100mg) and B12 (5000) for 1 month was associated with a reduction in total symptoms score (TSS: pain, burning, tingling, and numbness). Mean TSS significantly decreased from 4.7 to 2.99 after only 14 days of treatment, and decreased further to 2.37 at the end of the 30 day treatment period. [J Pharmaceutical Sci and Community 201;13:91-104]


Synergistic effect with analgesics and other pain-relieving agents

The B vitamins have also been found to extend the effect of nociceptive pain treatment by NSAIDS, with potent activity against neuropathic pain,” Lam noted.


In the randomized, double-blind controlled DOLOR study, twice-daily administration of high-dose vitamin B complex (B, 50mg, B6 50mg and B12 1,000) in combination with diclofenac 50 mg was found to provide full pain relief earlier than diclofenac monotherapy in 372 patients with acute lumbago. Furthermore, the combination therapy yielded superior results in pain reduction and in improvement of mobility and functionality. (Figure 2) [Curr Med Res Opin 2009;25:2589-2599]


About 60 percent of patients have pain of mixed pathophysiology”

As the study population comprised patients with mixed pain, it may be inferred from the results that FDCs of B vitamins are useful in treating low back pain [disease-targeted]regardless of whether the pain is nociceptive or mixed nociceptive and neuropathic in origin, rather than just for patients with neuropathic pain,” commented Lam.


"In the primary care setting, if the doctor is unable to determine whether the patient has nociceptive or neuropathic pain, prescribing FDC B vitamins is still recommended. This is because about 60 percent of patients have pain of mixed pathophysiology, and for every case of pure neuropathic pain seen by a GP or orthopaedic specialist, there are more than six cases of mixed pain,” Lam advised.

Such high-dose FDCs of B vitamins are also safe and effective in paediatric patients,” he added.


The adjuvant effect of the B vitamins was demonstrated in a clinical, comparative, randomized, double-blind study of 56 children aged 4-12 year who underwent paediatric ambulatory surgery (circumcision, tonsillectomy, inguinal hernioplasty or orchidopexy).Better pain score was recorded in children who received paracetamol plus B vitamins compared with those who received paracetamol alone during the immediate postoperative period and at the time of discharge. Of those who received the combination, 58 percent had a pain score of <2 during the immediate postoperative period and 89 percent were discharged with a pain score of 1 (vs 42 and 11 percent, respectively, with paracetamol alone). [Cir Cir2010;78:400-409]


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