Peripheral Neuropathy: Part Four

Examining Other Nutraceuticals




ALC has “very persistent analgesic effects when supplemented via diet”, and has been well studied (in animal models) for treating neuropathic pain conditions. 


In the case of ALC, animal studies led to human studies which tested oral ALC in patients with pain conditions, particularly DN and CIPN. “ALC was effective and well tolerated in improving neurophysiological parameters and in reducing pain over a 1-year period.”


In another human study, researchers “evaluated two 52-week randomized placebo-controlled clinical diabetic neuropathy trials testing two doses of acetyl-l-carnitine (ALC): 500 and 1,000 mg/day”. These studies found that ALC treatment was effective at “alleviating symptoms, particularly pain, and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy”.


Since ALC is an amino acid it should be taken on an empty stomach, and since it can raise dopamine (which improves the mood) it should not be taken after dinner as it could impede sleep.




NAC, like many of the compounds discussed, has both antioxidant and anti-inflammatory activities, and can also support immune function by raising glutathione levels in the body. In clinical trials NAC supplementation “led to an amelioration of neuropathic conditions”.


In other studies, NAC was combined with a drug (pregabalin) given to patients with DN, and led to “an overall improvement in neuropathy conditions”. This significant improvement was not the same in those given a placebo along with the drug “defining a positive role in NAC as adjuvant therapy”.


Patients with CIPN, in another clinical study, showed a reduction in incidence and severity of nerve pain when given NAC supplementally. “Thus, the results obtained confirm the role of NAC as an analgesic and neuroprotective compound for the treatment of, for example, neuropathic pain conditions, such as DN and CIPN, in a diet-supplementation-based therapy.”


Like ALC, NAC is an amino acid that can also raise dopamine, so it also should be taken between meals and avoided after dinner.


Fatty Acids


Omega 3’s


The EPA and DHA components of omega 3 fatty acids both mediate inflammation in the body and modulate pain stimulus.


In a human study involving 57 women undergoing chemotherapy (paclitaxel) for breast cancer “the administration of omega 3 fatty acids as oral supplements caused a reduction in paclitaxel-induced neuropathic pain in terms of incidence, with the risk of 70% lowered in omega-3 treated group”.


Patients were given 4 grams of omega 3’s daily. Note that this does not mean 4 grams of fish oil, as fish oils vary wildly in the amount of DHA and EPA they contain. This dose represents 4,000 mg of mixed DHA/EPA daily. Though one may find that they can get away with a lower dose if using krill oil, since it absorbs five times better than conventional fish oils, and unlike regular fish oil, actually enters the cells to do its work. 




Palmitoylethanolamide is another type of fatty acid, recently brought to market as a natural pain reliever, due to its anti-inflammatory activity and its ability to regulate pain mechanisms. It is found naturally occurring in a variety of foods including egg yolk, peanuts, and soybean lecithin.


In a mouse model of neuropathic pain “PEA administration led to reduced thermal hyperalgesia and mechanical allodynia”.


This benefit was confirmed in several human studies with patients suffering from neuropathic pain conditions. In another human study, patients with fibromyalgia were treated with PEA accompanying two drugs designed to treat nerve pain (duloxetine and pregabalin). Those receiving the added supplemental PEA showed better results in pain relief than those only taking the drugs. 


Alpha-Lipoic Acid


ALA is an antioxidant compound found in the mitochondria (where cellular energy is produced), and so is involved in energy production.


In clinical studies it has proven useful protecting against diabetes, neurodegeneration and neuropathy. With regards to neuropathic pain, ALA has successfully treated such pain in those suffering from DN and CIPN.


“For example, in a clinical trial, 460 patients with mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy were treated with ALA or placebo once daily for four years. ALA administration led to a clinically meaningful improvement and prevention of the progression of neuropathic pain conditions.”


Though not an amino acid, ALA should be taken on an empty stomach for best results (at least 30 min before eating or 2 hours after).




We have covered a lot of material here and the important thing to remember is that each of the substances discussed was usually tested in isolation (or with some drugs). This means that if one were to combine a number of the aforementioned compounds they might find even more dramatic results. 


This idea is supported by a study done with an Italian therapeutic product called OPERA® (GAMFARMA srl, Milan, Italy) which “showed an improvement of CIPN symptoms without toxicity or drug interactions”. This product is a combination of ALA, bromelain, and MSM. (Source) This kind of combination could be put together by anyone and is the kind of approach that I recommend.


(Source for the majority of this material: The Influence of Dietary Supplementations on Neuropathic Pain; Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; Life 2022,Published: 27 July 2022


(Author: All newsletters and blogs are written by Ken Peters who has worked as a nutritional consultant for the last 30 years, and as product designer for NutriStart for the last 25 years.  He has also authored two books – Health Secrets Vol. 1&2.  He may be reached at:

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