Evidence Scant on Nutraceuticals for Neuropathy in Diabetes
Written by Editor   
Tuesday, January 10, 2017 08:38 AM

News Bite:  The only therapeutic strategy shown to prevent development or curtail progression of diabetic neuropathy is tight glucose control.  There are numerous therapeutics for the pain associated with such neuropathy.  Nearly 25% of all diabetic patients are affected by neuropathy.  There is growing interest in nonpharmaceutical approaches to the treatment of both diabetic neuropathy itself and the associated pain.  This article looks at some.

 


There is currently no specific treatment approved for diabetic neuropathy, a huge unmet clinical need since up to half of all patients with diabetes will eventually develop neuropathy.

Part of the problem is that there is no clear path to successful approval of any such agents, with ongoing arguments about which clinical end points would be most relevant in trials. The only therapeutic strategy shown to prevent development or curtail progression of neuropathy is tight glucose control.

There are, however, numerous therapeutics for the pain associated with this complication, which is said to affect up to a quarter of all patients with diabetic neuropathy. But even the approved treatments for diabetic neuropathy pain are not ideal. “None affords complete relief, even when used in combination," according to the latest American Diabetes Association Standards of Care, published at the beginning of this year.

As a result, there is growing interest in nonpharmaceutical approaches to the treatment of both diabetic neuropathy itself and the associated pain, with a plethora of vitamins, vitamin complex combinations and other agents emerging that purport to affect this debilitating complication of diabetes.

What is the scientific evidence that these "nutraceuticals" can actually help? The problem is there is no unequivocal evidence based on randomized controlled trials that [nutraceuticals] slow or reverse nerve damage in diabetes.  But he says there may be a rationale for the use of certain vitamins in patients with diabetic neuropathy who are actually deficient — such as vitamin D or vitamin B12 — and such people may benefit from these vitamins. Vitamins can be effective in treating neuropathies that are due to vitamin deficiencies; unfortunately, most neuropathies are not caused by a vitamin deficiency.  No nutraceuticals are approved by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA), for the treatment of diabetic neuropathy or associated pain, but several such products are available over the counter.

Treating Vitamin D or B12 Deficiencies

There is a clear rationale for replacing vitamin D and B12 if there is a deficiency, which is common in colder countries having limited sunshine in the winter (and which therefore has an effect on vitamin D levels) and where patients with diabetes commonly receive metformin (which can lower levels of vitamin B12).

There is, however, no evidence that these are helpful if individuals have normal levels of these vitamins, though recent research conducted in Pakistan showed that a single, high dose of intramuscular vitamin D was safe and effective for patients with painful diabetic neuropathy.  In that study, 143 patients with predominantly type 2 diabetes and diabetic neuropathy pain received a single intramuscular injection of 600,000 IU vitamin D. At baseline, 40% of patients had vitamin D deficiency (25 OH vitamin D < 20 ng/mL).  Pain scores improved the most at 10 weeks and remained lower than baseline levels until the study end at 20 weeks. 

α-Lipoic Acid and the NATHAN 1 Study

Another nutraceutical claimed to be of some benefit in diabetic neuropathy is the antioxidant α-lipoic acid (ALA, also known as thioctic acid), which is approved for use in Germany for neuropathic pain.

In a large study called NATHAN 1, 460 patients with mild to moderate diabetic distal symmetric sensorimotor polyneuropathy received 600 mg/day of α-lipoic acid (Thioctacid HR, MEDA Pharma) or placebo for 4 years.

The study failed to meet its primary efficacy end point (a composite of pain scores) or improve nerve conduction. But the patients treated with α-lipoic acid did have improvements in some symptoms and less progression of impairment, compared with patients who received placebo, and the agent was well tolerated.

In a post hoc analysis they showed that patients with normal baseline blood pressure and weight, but older age, longer duration of diabetes and neuropathy, and a history of CVD were less likely to have progression of neuropathic impairment after 4 years of treatment with α-lipoic acid than those on placebo.  And patients who also received ACE inhibitors were more likely to have improved heart rate during deep breathing (a measure of cardiac autonomic function).  “Thus, the drug may be particularly suitable for the elderly patient with a history of CVD and ACE-inhibitor treatment and both more severe diabetes and neuropathy who cannot meet individualized glycemic targets,” the researchers say.  In other words, the worse a patient was, the better they responded to treatment with ALA.

Vitamin Combinations: Metanx and NutriNerve

There are also products that combine different B vitamins and purport to be effective in diabetic neuropathy and its associated pain, but clinical-trial evidence for efficacy of any of these is currently sparse.

In a recent trial of patients with type 2 diabetes and neuropathy, Metanx (Nestle Health Science-Pamlab), which consists of capsules that contain a cocktail of B vitamins — 2.8-mg L-methylfolate (vitamin B9), 35-mg pyridoxal 5'-phosphate (vitamin B6), and 2-mg methylcobalamin (vitamin B12) — did not meet its primary end point of improved vibration-perception threshold, although patients reported symptom improvement, and adverse events were infrequent.

In the study 214 patients were randomized at centers in Alabama, Louisiana, Nebraska, and Texas to receive this B vitamin combination or placebo daily for 24 weeks.  Metanx did show a clinically significant improvement in Neuropathy Total Symptom Score (NTSS-6), a secondary end point, among those taking Metanx compared with those on placebo.

Currently…the only agents approved for the treatment of symptomatic diabetic peripheral neuropathy in the US are duloxetine and pregabalin, which do not affect nerve conduction, have mechanisms of action unrelated to the pathophysiology of diabetic neuropathy, and only address pain relief. There is a third medication approved in the United States for diabetic neuropathy pain, an opioid called tapentadol.

Another nutraceutical, NutriNerve, consists of capsules that contain 150-mg α-lipoic acid, 130-mg gamma-linoleic acid, 75-mg vitamin B1 (benfotiamine), 85-mg vitamin C, 1-mg vitamin B12 (methylcobalamin), and 500-IU vitamin D (cholecalciferol).


Source: http://www.medscape.com/viewarticle/871621