Peripheral Neuropathy: Part Two
Herein we examine the vitamins and minerals that have a relationship to the development and reversal of nerve damage. Before we get started here is a reminder, from Part 1, as to which biological mechanisms are involved in the process of nerve damage: “The mechanism behind the damage of nervous system structures involves mainly oxidative stress and altered ion channel activity, but also mitochondrial damage, microtubule disruption, myelin sheath damage, DNA damage, neuroinflammation and other immunological processes.”
With that in mind, let’s look at what science has to say on the subject of nutrients and PN.
Of the B-vitamins there are four which apply to our condition: B1 (thiamine); B-6 (pyridoxine); B-9 (folic acid); and B-12 (cyanocobalamin). These are of particular interest because they all “are known to play an extremely relevant role in a variety of processes, such as DNA and RNA synthesis, metabolism, immunity and neuroprotection”.
In both human and animal studies these B vitamins have proven beneficial in alleviating neuropathic pain resulting from diabetes, or chemotherapy-induced neuropathic pain (CIPN). Some studies used only one B vitamin (B-6 or folic acid), which was somewhat effective, but the best results were obtained when a mix of all of them were used.
Folic acid, also known as folate, serves as a “methylator” in the nervous system, and so it was tested alone in a mouse model of neuropathic pain, and it significantly lowered pain levels.
Having low levels of any of these four B vitamins is considered to be a risk factor for CIPN, and in a double-blind study vitamin B-6 reduced CIPN. Vitamin B-12, also a methylator, is known to be required for nerve repair and myelination and so it’s a no-brainer to include it among the most important B vitamins for treating neuropathic pain.
Now, all this research related to B vitamins is essentially old-school. We now know that at least a third of humans are poor methylators, which means, in part, that they cannot easily convert folic acid, thiamine, pyridoxine, and cyanocobalamin into the methylated versions required by the body for nerve repair (amongst other functions). Thus, anyone seeking to treat PN should use the “bioactive” forms of these vitamins to ensure they get the best results.
These forms are known as methylfolate (folic acid), benfotiamine (B-1), pyridoxal 5′-phosphate (B-6), and methylcobalamin (B-12). Both benfotiamine and methylcobalamin, have already proven themselves especially effective in clinical studies done on nerve pain.
And one study combining methylfolate, methylcobalamin, and pyridoxal-5-phosphate, achieved significant improvements in treating symptoms of neuropathy in diabetics, and improving their quality of life. (Source)
Vitamin C is required for collagen synthesis and serves immunological functions along with being neuroprotective. Of course it, like the B vitamins, also serves many other functions, but here we will focus on those functions of vitamins that are germane to our subject.
And, in the case of vitamin C, its function as a powerful antioxidant has shown it to be effective in aiding in pain management. “Several studies confirm the efficacy of vitamin C in reducing pain derived from neuropathic pain conditions.”
We have at least two studies done with humans suffering from diabetic neuropathy (DN) in which, after 12 weeks of treatment with vitamin D, “the reduction in pain in the vitamin-treated group was remarkable”.
(One of the most therapeutic forms of vitamin C is Liposomal, the only delivery form that ensures vitamin C enters the cells.)
No surprise to see vitamin D on the list since I believe almost every ailment known to man can be linked somehow to vitamin D deficiency. As vitamin D receptors are found throughout the central nervous system, it is believed that vitamin D “may be involved in a large number of mechanisms underlying pain development”.
While the mechanism of action of vitamin D has yet to be established, the fact that these receptors in the CNS are involved in converting stored vitamin D into its active form indicates the importance of the nutrient at this location. And, vitamin D is known to be required for the regulation of many processes “implicated in pain manifestation”.
With these ideas in mind, researchers have looked for the relationship between vitamin D deficency and neuropathic pain conditions, including CIPN (chemotherapy induced peripheral neuropathy) and DN (diabetic neuropathy), two conditions frequently accompanied by vitamin D deficiency.
Two studies have shown supplementing with vitamin D to “counteract pain derived from DN caused by diabetes mellitus”, and a third found “a significant decrease in pain scores in the treatment group compared with the placebo”.
With regards to CIPN, at this point all that can be confirmed from actual studies is that one is more prone to developing neuropathic pain as a result of chemotherapy, if they enter into it already deficient in vitamin D. However, no studies exist that indicate taking vitamin D after the condition has developed will alleviate pain. Thus it is suggested that prior to beginning chemotherapy one ensure they have built up their vitamin D levels.
Minerals are obviously essential for countless functions in the body, including antioxidant activity, bone formation and hormone synthesis. In our examination of nutrients related to PN two minerals stand out as “potential therapeutic instruments against neuropathic pain conditions”. These are magnesium and zinc.
Required for many intracellular processes, magnesium carries signals throughout the body due to its influence on ion transport.
One study on magnesium and PN found that “magnesium is able to antagonize the NMDA receptor, counteracting its activity in neuropathic pain development”. (“The N-methyl-D-aspartate (NMDA) receptor is a receptor of glutamate, the primary excitatory neurotransmitter in the human brain.” Source)
In another study (rat model of DN), supplementing with magnesium, by way of down regulating NMDA, led to a reduction in a form of PN called allodynia. (“Allodynia is defined as pain due to a stimulus that does not normally provoke pain.” Source)
In one human study, intravenous magnesium (sulfate: same form as epsom salts) proved so effective at lowering neuropathic pain that opioid use could be reduced. (Source)
Unfortunately, not all studies found magnesium to be effective for treating neuropathic pain, but given that some did, it certainly should be on the list of necessary nutrients.
Zinc treatment is used medically “as treatment for different diseases, such as alcohol-related liver disease, sickle cell anemia, macular degeneration, and neuropathic pain”.
Serving as an antioxidant compound, and involved in the activation of hundreds of genes, zinc deficiency is associated with DNA damage, and immune suppression. (Here we see zinc address three of the mechanisms of PN.) And since pain is associated with inflammation, it may be zinc’s role in reducing inflammatory compounds that makes it useful for treating PN.
“In rats with induced neuropathic pain, the supplementation of zinc induced a reduction in pain.” In another rodent study, zinc proved helpful in reducing allodynia due to CIPN.
However, there is not much in the way of clinical studies on this subject done with humans. Nonetheless, there is a correlation between zinc deficiency and neuropathic pain in those with DN, and supplementing with zinc delayed pain manifestation in those with CIPN.
With the prevalence of research on the gut microbiome it is not surprising that some researchers thought that the gut-brain axis may “play a relevant role in such conditions”.
This link was examined because it is already known that the gut-brain axis regulates a wide range of functions “such as the modulation of pain, metabolic and neurological signaling, inflammation and others”.
Studies have examined the role of probiotics for treating DN and CIPN. Particularly with CIPN it is known that chemotherapy agents strongly alter the gut microbiome in a negative way.
In a mouse study, the probiotic formulation SLAB51 (composed of nine bacterial strains and commercially available as SivoMixx) was tested to see how it affected CIPN. “SLAB51 administration contributed to gut integrity in CIPN mice. In fact, the preservation of gut functionality and physiology led to the prevention of nerve fiber loss, a reduction in inflammation and the overall relief of neuropathic pain conditions.”
Other studies have found specific probiotics, and probiotic combinations, to also be helpful in reducing pain and inflammation, particularly visceral pain: “clostridium butyricum, Roseburia hominis, Bifidobacterium infantis 35624 and VSL#3 counteracted visceral pain in rats decreasing hypersensitivity induced by inflammation or stress.”
As far as human studies, the positive effects of probiotics “have been confirmed in chronic pain patients. The administration of Lactobacillus reuteri DSM 17938 in a double-blind controlled trial reduced the frequency and intensity of abdominal pain in children.”
Again, more research needs to be done, but clearly anyone with any kind of nerve pain needs to ensure that at least their microbiome is in good shape (using something like LactoSpore Supreme), and for serious conditions they will want to ensure the gut-brain axis is functioning well (our Provide Balance Smoothie Mix is designed to support this axis). Whil those with severe conditions may want to seek out some of the formulas listed above.
In Part 3 I will look at herbs, amino acids and fatty acids, which contribute to soothing and healing our damaged nerves.