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Which supplements help with nerve pain? The second part of this article series will discuss which supplements are favored by scientific evidence for relieving neuropathy symptoms from diabetes (diabetic neuropathy).
This is the second part of the blog series on non-pharmacological and natural treatments for nerve pain. Click here for the first article. Our collaborative journal article, published in 2019, serves as the primary reference source for this blog series. If you are unable to view the official published article via digital library access, please click here for free access to the final Word/Google Docs version of the article.
This blog series will be highlighting the important points of the scientific review. In this Part 2, there is bonus information that was not published in the journal article.The blog contains health education information but is not intended to diagnose or treat any medical condition. I’m acting in the capacity of a medical writer and expert, not as a personal medical doctor.
--Danielle Zelnik, MD, ABPMR, ABOIM (blog author, review article co-author)
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drzelnikmd.com
Supplements- B-Vitamins & Folate
- Vitamin D
- Alpha-Lipoic Acid
- Acetyl-L-Carnitine
- Gamma-Linolenic Acid
- Magnesium
B-Vitamins & Folate
Deficiency of B vitamins, themselves, can cause neuropathy. Both Vitamin B6 deficiency and excessive intake can cause neuropathy. Therefore, avoid taking a B6 supplement unless your doctor advises you to. Your doctor will test you for vitamin deficiency to rule this out as a cause or contributing factor for your neuropathy. They will likely check your Vitamin B12 levels if you are using the popular diabetes medicine, metformin, as its use has been associated with deficiency.
The use of Vitamin B12 in the form of Methylocobalamin (MC) appears to reduce symptoms of diabetic neuropathy, even in those with normal serum B12 levels. MC has been studied and used in Asian countries for neuropathy treatment, either alone, or in combination therapy via oral (by mouth) or intravenous routes. Oral MC 500 micrograms three times daily (NOT TO BE CONFUSED WITH milligrams) has shown efficacy in a small double-blind randomized controlled trial.
Metanyx® is a prescription medical food product for treatment of painful diabetic neuropathy, containing methyl folate, MC, and pyridoxal phosphate. It is taken under a doctor's supervision, and a study demonstrated that users reported significant improvement in neuropathy symptoms and quality of life.
A study showed oral folate supplementation 1 milligram daily for 16 weeks compared with placebo increased sensory and motor nerve responses in participants with diabetic neuropathy. Methylfolate is the active form of folate, widely available online or over-the-counter.
Vitamin D
Vitamin D deficiency, alone, does not appear to cause peripheral neuropathy. Nevertheless, it is an independent risk factor for developing diabetic neuropathy. Ask your doctor about checking your Vitamin D level if you are diabetic. Doctors commonly prescribe 50,000 international units (IU) of vitamin D weekly to treat deficiency. Some doctors use ultra high doses exceeding 50,000 IU; however, there is a risk of vitamin D toxicity. Doses lower than 50,000 IU are used to treat insufficiency, a lower level than expected level, but not in the deficient range. Additionally, Cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) are widely available as supplements. Consult with your doctor if you plan on taking more than 2,000 IU daily for supplementation.
51 insufficient patients with painful neuropathy took oral vitamin D3 2,000 IU daily for 3 months, resulting in a 50% decrease in their pain levels. Those with deficiency and neuropathy were studied taking oral 50,000 IU vitamin D3 once weekly for 8 weeks with improvement in their symptoms. Researchers also administered a single intra-muscular dose of ultra-high vitamin D3 (600,000 IU) to subjects with painful diabetic neuropathy, regardless of baseline vitamin D level, and found maximally reduced neuropathy pain and symptoms at 10 weeks after receiving the dose.
Alpha-Lipoic Acid
Alpha-lipoic acid (ALA), also known as thioctic acid, has been is used in Germany to treat diabetic neuropathy, mostly in the intravenous (IV) form. Oral ALA has been reported (as in this review article) to be inefficiently absorbed in the body with supplement uptake lowered by food intake.
A 2012 meta-analysis of controlled trials of ALA, favors the IV form over the oral form at a dose of no more than 600 mg daily over a period of 3 weeks, as higher doses showed no further improvement and were associated with greater incidence of side effects. The IV form was recommended over the oral due to a subgroup analysis, showing both were significantly effective at reducing neuropathy symptoms; however, the degree of symptom reduction was clinically relevant (greater than 30% effect) for the IV ALA but not for the oral ALA.
In a practical sense, there are not a lot of doctors in the United States offering IV ALA. Therefore, oral supplementation makes the most sense here. No upper limit for ALA has been established, but clinical trials have used oral ALA up to 2400 mg daily with no reported adverse effects compared with placebo. On the conservative side, an oral dose of ALA 600 mg at night for 4–6 weeks is reasonable and low risk to try. The authors of the Korean study cited below (in the gamma-linolenic acid section), suggested a 12 week trial due to a plateau in efficacy seen around 5 weeks of use. ALA has potential to interfere with thyroid hormone, so it is not recommended in those taking thyroid medication.
Acetyl-L-Carnitine
Like ALA, Acetyl-L-carnitine (ALC) has been proposed to play a role as an antioxidant and regulator of cell energy metabolism. ALC penetrates the blood-brain barrier, is effective when taken orally, and has a favorable safety profile. Multiple studies have demonstrating efficacy of ALC for neuropathy compared to placebo. For example, an analysis of 2 double-blinded randomized controlled trials of 341 participants compared oral doses of 500 mg and 1,000 mg taken three times daily versus placebo. ALC produced a significant reduction in pain scores at 26 and 52 weeks in those taking the 1,000 mg dose. Studies indicate that it might take up to 3 months to see an effect from ALC use. ALC doses from 500-3000mg per day produce minimal side effects, aside from rare gastrointestinal intolerance. Given the data, a three-month trial of ALC 1,000 mg three times daily (total 3,000mg daily) can be considered. ALC should not be used in those with taking thyroid hormone, those with a history of seizures, and those on anticoagulants. Consult with your doctor or pharmacist for more information.
Gamma-Linolenic Acid
Gamma-Linolenic acid was not included in last year's review article due to limited clinical trial evidence but deserves an honorable mention, as there is a recent study out of Korea comparing GLA and ALA. GLA is found in evening primrose oil, black currant seed oil, and borage seed oils.
The recent study, published in Diabetes and Metabolism Journal, compared 360mg daily GLA and placebo with 600mg daily ALA and placebo in 73 randomized participants for 12 weeks. The GLA came in the form of a supplement of evening primrose oil that required participants to take 4 capsules twice daily to get the 360mg of GLA. On the other hand, only one 600mg capsule of ALA was taken daily. Each placebo was identical in appearance and dosing to the opposing supplement. This was done perhaps to avoid bias of one treatment group taking 8 capsules as opposed to the other taking only 1 daily. There was a significant improvement in pain scores from baseline in each group with no difference between the two treatment groups (termed "non-inferiority"). However, the ALA appeared to perform better in relieving other neuropathy symptoms, such as numbness and tingling, than the GLA.
An older study showed improved nerve function parameters and strength in those with mild diabetic neuropathy taking 480mg GLA for 1 year.
Luckily, there are formulations of GLA (such as borage seed oil) that deliver the 360-480mg mg dose without needing to consume ridiculous amounts of capsules. Just look at the back label for the actual amount of GLA in a supplement and the serving size to calculate how many needed get to at least 360mg daily.
Magnesium
A direct causal relationship between magnesium levels and neuropathy has not been clearly established. There is weaker evidence suggesting a correlation between low magnesium levels and abnormal nerve study results. A study tracking Type 1 diabetics taking 300 mg daily magnesium glycinate for 5 years revealed evidence that it slowed down the progression of neuropathy. There is a need for more studies to determined if taking magnesium is useful or not for painful diabetic neuropathy.
Magnesium supplementation can cause a severe laxative effect and gastrointestinal symptoms. It is not recommended for those who have kidney problems. Magnesium-rich foods can easily be obtained in the diet without the need for supplementation in most cases. Consult with your doctor for more information.
Conclusion
Various supplements have been shown to improve neuropathy symptoms. The next step is to discuss these ideas with your healthcare provider.
Stay tuned for the next part of the blog series, which goes over cannabis and cannabis-related supplements for neuropathy!
Primary Reference
Baute V, Zelnik D, Curtis J, Sadeghifar F. Complementary and Alternative Medicine for Painful Peripheral Neuropathy. Curr Treat Options Neurol. 2019;21(9):44. Published 2019 Sep 2. doi:10.1007/s11940-019-0584-z
Secondary reference citation links are embedded in the blog article.