Neuropathy – A Review of Natural Treatments and Drug Risk Factors

Vitamin E

Although a number of trials have suggested that oral administration of vitamin E can prevent chemotherapy-induced peripheral neuropathy23–26, a 2015 trial and a 2016 meta-analysis did not find any such benefit.27,28 One trial in 21 diabetics with mild or moderate peripheral neuropathy found that 6 months of taking 900mg of vitamin E led to significant improvements in 2 out of 12 nerve conduction electrophysiological parameters.29

Glutathione (GSH)

Two trials of intravenous glutathione also showed decreased incidence of chemotherapy-induced polyneuropathy. One trial administered oxilaplatin and the other cisplatin. Neither trial noted reduction in tumor response, indicating that glutathione does not seem to interfere with the efficacy of the applied chemotherapies.30,31 However a larger and more recent study found no such benefit when patients were given the combination of paclitaxel and carboplatin.32

Many supplements mentioned in this article are involved either as precursors or as recyclers of glutathione. It may be that part of their benefits are due to enhancing glutathione activity. To the best of our knowledge there has never been a trial testing oral glutathione in the treatment of other kinds of neuropathy. While studies have shown that oral glutathione does indeed raise blood levels of glutathione, somewhat poor absorption is a consideration. Liposomal glutathione or acetyl glutathione overcome issues of absorption and would be obvious candidates for a clinical trial.

Acetyl-L-Carnitine (ALC)

An analysis of two randomized-controlled trials totaling 1,257 patients with established diabetic neuropathy found that acetyl-L-carnitine in doses of either 500mg or 1,000mg twice a day improves a number of measures. These improvements included pain, nerve fiber regeneration, and vibration perception.33

B-Complex Vitamins

A 2005 review found that while vitamin B-12 may be beneficial, more high-quality, double-blind randomized controlled trials are needed to confirm the effects of vitamin B12 on diabetic neuropathy.34 Vitamin B12 deficiency in diabetics has been linked to metformin use, and vitamin B12 replacement has caused symptomatic improvement among patients with severe diabetic neuropathy.4,5 A small study suggested that chronic spinal cord injury patients may be at risk for B12 deficiency, and that B12 supplementation may lead to improvement in symptoms.35 A 2008 review found that there is insufficient evidence to determine whether or not B-complex vitamins are beneficial.36 A mouse model of spinal cord injury found folate administration regulated axonal regeneration. The amount of regeneration followed a biphasic curve, meaning there was an optimal dose where if you go either higher or lower than that, the benefits decline. The authors suggest that folic acid and possibly other nontoxic dietary methyl donors may be useful in clinical interventions to promote brain and spinal cord healing.37 Of course, there is no clear way to translate this study into an optimal dosing for humans.

We suggest it may be useful to go  back and reanalyze trials looking only at the subgroup of patients who were on metformin. A more obvious benefit from B vitamins might be seen.

Alpha-Lipoic Acid (ALA)

A meta-analysis found alpha-lipoic acid beneficial in the treatment of diabetic peripheral neuropathy. Trials that used TSS scores were analyzed, and the authors found a mean reduction in TSS scores of 2.26 in favor of alpha-lipoic acid administration. A TSS score of 0 means there is no pain, burning, paresthesia, or numbness. A score of 14.64 means all four of these symptoms are severe and more or less continuous. Subgroup analysis found that 3 weeks of 600mg intravenous alpha-lipoic acid resulted in a mean reduction of 2.81 in TSS scores. Oral administration of >=600mg of alpha-lipoic acid for 3 to 5 weeks led to a mean reduction in TSS scores of 1.78. It is unclear if this improvement from oral administration met the definition of being “clinically relevant”.38 Given the short durations of oral administration seen in this analysis, perhaps longer durations may reveal a more obvious cumulative benefit. Though safe when done properly, intravenous administration of ALA may be unsafe if doses are excessive, improperly diluted, or if patients are not properly monitored for hypoglycemia.39

While it is sometimes claimed that alpha-lipoic acid can cause biotin deficiency, this appears to be unsubstantiated and based off of extrapolation from a flawed animal study. In fact, oral ALA may actually stimulate gut bacteria to synthesize biotin.40

Some individuals claim sensitivity to alpha-lipoic acid. In some rare instances this sensitivity can apparently be severe involving things like extreme fatigue or cognitive impairment. To the best of our knowledge this kind of severe sensitivity has never been reported in any medical journals. It is noted – perhaps exclusively – by individuals who suspect they suffer from mercury poisoning. Since alpha-lipoic acid has mercury-chelating properties, it is possible that mobilization of mercury could be an underlying cause of side effects from alpha-lipoic acid. People with suspected mercury poisoning should exercise caution before taking alpha-lipoic acid. Safe dosing of alpha-lipoic acid for the purposes of mercury detoxification is potentially very different from dosing for other purposes.

CoQ10 (Ubiquinone)

A randomized controlled trial gave 400mg of CoQ10 or a placebo to patients with diabetic neuropathy for 12 weeks. Significant improvements compared to controls were noted on several different measures. These included improvements in neuropathy symptoms score (from 2.5 ± 0.7 down to 1 ± 0.8, p<0.001) and neuropathy impairment score (from 5.5 ± 4 down to 3.1 ± 2.6, p<0.001). No significant adverse effects were noted.41 An obvious candidate for a clinical trial would be CoQH (ubiquinol), which is the active form of CoQ10, and research suggests it is more effective than CoQ10 for a number of conditions. Perhaps the same would apply for neuropathy.

Vitamin D

Vitamin D levels have been found to be significantly lower in patients with diabetic neuropathy than in healthy controls. Perhaps this could be explained by factors such as decreased physical activity, and hence decreased sun exposure. In any case, according to some experts, while there have not yet been any trials testing vitamin D in the treatment of neuropathy, it is still a good idea to take it given its safety and low cost.42 This is also supported by a controlled animal study where vitamin D3 improved functional recovery of spinal cord injuries.43 Another study found vitamin D is involved in the regeneration of myelin.44

Lithium Carbonate

A trial of lithium carbonate failed to improve the functional outcomes and neurological classifications in SCI patients. However it did find improvements in neuropathic pain symptoms, including 2 out of 20 patients having their pain completely eliminated by the end of 6 weeks.45 Another clinical trial focusing on neuropathic pain has been completed, but the results do not yet appear to be published.46

Spinal Decompression Therapy

Some small studies suggest that various spinal decompression therapies may reduce disk-related neuropathic pain, and that an increase in disk height may be associated with a reduction in pain. Larger controlled studies appear to be warranted.47–49

Pulsed Electromagnetic Field Therapy (PEMF)

A number of studies suggest a possible role of pulsed electromagnetic fields (PEMF) in the treatment of neuropathies. In some instances the field is applied to the site of pain, and in other instances it is applied to the brain. In some instances it appears that the analgesic effect is short lived, implying regular treatment may be needed to sustain benefits if this proved to be a viable therapy. Hence long-term safety of PEMF therapy needs investigation.50–57

Epidural Stimulation

The Christopher and Dana Reeve Foundation has discovered that implanting a device that gives epidural stimulation resulted in dramatic improvements in four patients with chronic motor complete spinal cord injury.58 They are currently raising funds to conduct a clinical trial.

Low Level Laser Therapy

In a trial of 60 patients with diabetic peripheral neuropathy low level laser therapy appeared to provide some benefit compared to controls. Further studies are needed to test different types of lasers, as well as different dosage and exposure levels required in different phases of neuropathic care, so as to obtain reproducible results.59

Combination Approaches to Neuropathy

Since most of these supplements have little to no side effects, using them in combination to treat neuropathy becomes a feasible and sensible option. In fact, some studies have already started to go this route.

Alpha-Lipoic Acid and Gamma-Linolenic Acid

One study tested a combination of alpha-lipoic acid and gamma-linolenic acid in patients with neuropathic pain from compressive radiculopathy syndrome from disc-nerve root conflict. Patients were either given these two supplements in conjunction with six weeks of a rehabilitation program, or else they were only assigned to the rehabilitation program. Statistically significant decreases in neuropathic symptoms and deficits were found in the supplement group relative to the non-supplement group.60

A Vitamin and Mineral Combination Study

75 type 2 diabetes patients divided into three groups were given a combination of nutritional supplements. The first group received zinc (20 mg), magnesium (250 mg), vitamin C (200 mg) and vitamin E (100 mg). The second received the same nutrients, plus vitamin B1 (10 mg), B2 (10 mg), B6 (10 mg), biotin (200 μg), B12 (10 μg) and folic acid (1 mg). The third group received a placebo. By the end of four months an MNSI questionnaire showed the first group had their neuropathy symptoms decrease from 3.96 to 1.0. The second group from 3.45 to 0.64. And the placebo group from 2.54 to 1.95. There was no significant difference between the three treatment groups in MNSI examinations after 4 months of supplementation. The authors concluded, “These studies suggest that micronutrients supplementation might ameliorate diabetic neuropathy symptoms.”61 It would seem sensible to investigate higher doses for longer periods of time.

A Combination of Glutathione Precursors Study

In an open label study 43 patients with peripheral neuropathy were given a combination of alpha-lipoic acid, n-acetyl-cysteine, L-carnitine, selenium, and vitamin C. 26 patients were diabetic, and the rest had neuropathy of unknown origin. By 9 months symptom assessments found reductions in overall pain, burning pain, and numbness ranging from 66% to 70%.62

A Combination Commercial Product Survey

A company that sells a combination formula for neuropathy conducted an email survey of their customers. 450 customers responded. 78% of respondents reported a reduction in symptoms. 93.4% reported no side effects, and 0% reported severe side effects. The ingredients in this product are vitamins B1, B2, B6, B12, R-alpha lipoic acid, vitamin D, feverfew extract, oat straw extract, passionflower extract, and skullcap extract.63 One consideration is that perhaps people who had positive results were more likely to want to respond to the survey than others, thus producing a favorable bias. This survey is of course not a controlled study, but at least gives some additional confidence about safety.
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