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Diabetic peripheral Neuropathy


Diabetic neuropathy affects all peripheral nerves: pain fibers, motor neurons, autonomic nerves. It therefore necessarily can affect all organs and systems since all are innervated. There are several distinct syndromes based on the organ systems and members affected, but these are by no means exclusive. A patient can have sensorimotor and autonomic neuropathy or any other combination. Symptoms vary depending on the nerve(s) affected and may include symptoms other than those listed. Symptoms usually develop gradually over years.

Symptoms may include:

  • Numbness and tingling of extremities
  • Dysesthesia (decreased or loss of sensation to a body part)
  • Diarrhea
  • Erectile dysfunction
  • Urinary incontinence (loss of bladder control)
  • Impotence
  • Facial, mouth and eyelid drooping
  • Vision changes
  • Dizziness
  • Muscle weakness
  • Difficulty swallowing
  • Speech impairment
  • Fasciculation (muscle contractions)
  • Anorgasmia
  • Burning or electric pain


Despite advances in the understanding of the metabolic causes of neuropathy, treatments aimed at interrupting these pathological processes have been limited. Thus, with the exception of tight glucose control, treatments are for reducing pain and other symptoms.

Options for pain control include tricyclic antidepressants (TCAs), serotonin reuptake inhibitors (SSRIs) and antiepileptic drugs (AEDs). A systematic review concluded that “tricyclic antidepressants and traditional anticonvulsants are better for short term pain relief than newer generation anticonvulsants.”[2] A combination of these medication (gabapentin + nortriptyline) may also be superior to a single agent.[3]

The only two drugs approved by the FDA for diabetic peripheral neuropathy are the antidepressant duloxetine and the anticonvulsant pregabalin. Before trying a systemic medication, people with localized diabetic periperal neuropathy might relieve their symptoms with lidocaine patches.[1]

In addition to pharmacological treatment there are several other modalities that help some cases. These have shown to reduce pain and improve patient quality of life particularly for chronic neuropathic pain: Interferential Stimulation; Acupuncture; Meditation; Cognitive Therapy; and prescribed exercise.

Tricyclic antidepressants

TCAs include imipramine, amitriptyline, desipramine and nortriptyline. These drugs are effective at decreasing painful symptoms but suffer from multiple side effects that are dosage dependent. One notable side effect is cardiac toxicity, which can lead to fatal arrhythmias. At low dosages used for neuropathy, toxicity is rare, but if symptoms warrant higher doses, complications are more common. Among the TCAs, amitriptyline is most widely used for this condition, but desipramine and nortriptyline have fewer side effects.

Serotonin reuptake inhibitor

SSRIs include fluoxetine, paroxetine, sertraline and citalopram. These agents have not been FDA approved to treat painful neuropathy because they have been found to be no more efficacious than placebo in several controlled trials. Side effects are rarely serious, and do not cause any permanent disabilities. They cause sedation and weight gain, which can worsen a diabetic’s glycemic control. They can be used at dosages that also relieve the symptoms of depression, a common concommitent of diabetic neuropathy.

The SSNRI duloxetine (Cymbalta) is approved for diabetic neuropathy. By targeting both serotonin and norepinephrine, it targets the painful symptoms of diabetic neuropathy, and also treats depression if it exists. Typical dosages are between 60 mg and 120 mg.

Antiepileptic drugs

AEDs, especially gabapentin and the related pregabalin, are emerging as first line treatment for painful neuropathy. Gabapentin compares favorably with amitriptyline in terms of efficacy, and is clearly safer. Its main side effect is sedation, which does not diminish over time and may in fact worsen. It needs to be taken three times a day, and it sometimes causes weight gain, which can worsen glycemic control in diabetics. Carbamazepine (Tegretol) is effective but not necessarily safe for diabetic neuropathy. Its first metabolite, oxcarbazepine, is both safe and effective in other neuropathic disorders, but has not been studied in diabetic neuropathy. Topiramate has not been studied in diabetic neuropathy, but has the beneficial side effect of causing mild anorexia and weight loss, and is anecdotally beneficial.

Other treatments

lipoic acid, an anti-oxidant that is a non-prescription dietary supplement has shown benefit in a randomized controlled trial that compared once-daily oral doses of 600 mg to 1800 mg compared to placebo, although nausea occurred in the higher doses.

Though not yet commercially available, C-peptide has shown promising results in treatment of diabetic complications, including neuropathies. Once thought to be a useless by-product of insulin production, it helps to ameliorate and reverse the major symptoms of diabetes.

In more recent years, Photo Energy Therapy devices are becoming more widely used to treat neuropathic symptoms. Photo Energy Therapy devices emit near infrared light (NIR Therapy) typically at a wavelength of 880 nm. This wavelength is believed to stimulate the release of Nitric Oxide, an Endothelium-derived relaxing factor into the bloodstream, thus vasodilating the capilaries and venuoles in the microcirculatory system. This increase in circulation has been shown effective in various clinical studies to decrease pain in diabetic and non-diabetic patients.  Photo Energy Therapy devices seem to address the underlying problem of neuropathies, poor microcirculation, which leads to pain and numbness in the extremities

There has been experimental work testing the efficacy of a drug called sildenafil but this study described itself as an “isolated clinical report” and cited a need for further clinical investigation.

Tight glucose control

Treatment of early manifestations of sensorimotor polyneuropathy involves improving glycemic control. Tight control of blood glucose can reverse the changes of diabetic neuropathy, but only if the neuropathy and diabetes is recent in onset. Conversely, painful symptoms of neuropathy in uncontrolled diabetics tend to subside as the disease and numbness progress.

The mechanisms of diabetic neuropathy are poorly understood. At present, treatment alleviates pain and can control some associated symptoms, but the process is generally progressive.

As a complication, there is an increased risk of injury to the feet because of loss of sensation (see diabetic foot). Small infections can progress to ulceration and this may require amputation.

Metanx® is a prescription medical food for the dietary management of endothelial dysfunction in patients with diabetic peripheral neuropathy.

How is Metanx® different than over-the-counter vitamins?
Traditional over-the-counter vitamins are synthetic forms of the nutrients found in nature. This is the case for common B-vitamins such as folic acid, vitamin B6 and vitamin B12. Each of these must be converted into their natural, active forms before they can actually be used by the body’s cells for such vital functions as DNA production, cell reproduction and homocysteine metabolism.

B Vitamin Active Form
Folic acid L-methylfolate
Vitamin B6 Pyridoxal 5′-phosphate
Vitamin B12 Methylcobalamin

Metanx® is a prescription medical food and has a unique formulation providing the active forms of folate, vitamin B6 and vitamin B12 to manage the distinct nutritional requirements of diabetic neuropathy patients who often experience numbness, tingling, and burning sensations in their feet.

Each Metanx® tablet contains:
L-methylfolate 3mg
Pyridoxal 5′-phosphate 35mg
Methylcobalamin 2mg

The bioefficacy of one Metanx® tablet can be compared to taking 19 folic acid tablets (1mg each) 2 B12 tablets (1mg each), and 2 B6 tablets (25mg each).

Did you know?

Up to 50% of individuals are unable to fully convert folic acid into the active form of folate, L-methylfolate.

Metanx® is available to nutritionally manage endothelial dysfunction associated with numbness, tingling, and burning sensations in diabetic neuropathy patients.