Alpha Lipoic Acid Reverses Nerve Damage In Diabetics

Alpha-lipoic acid is a potent antioxidant that stands out from other treatments claiming to treat diabetes mellitus (DM). Pretty much, we can say that it has a disease-altering effect on DM (1). According to a study conducted on lipoic acid, there was a considerable improvement in the symptoms of diabetic neuropathy (damage to the nerves); the reports revealed a greater than 50% amelioration of the neuropathy improvement score (NIS), embracing both the sensory and motor deficits.

If you are a diabetic, you should already be having some knowledge of diabetic neuropathy (DN). If not, here is a brief heads up. It is a grim condition that seriously affects the quality of life, as it can make one wheelchair bound, leading to necrotic (dead) foot ulcers, gangrene, and foot or leg amputation in severe cases. It has a tendency to affect peripheral nerves (nerves running from various parts of the body to the brain and spinal cord and vice versa). These nerves include sensory nerves (which carry sensations from the body to the brain and spinal cord), motor nerves (which transmit messages from the brain and spinal cord to the rest of the body), and autonomic nerves (which supply the internal organs and control the unconscious/involuntary-derived functions of the body, for instance, heart rate, breathing movements, digestion, urination, etc.) (2)

Given that, we broadly categorize DN as:

Sensory neuropathy: Numbness (loss of sensation) that causes painless injuries and foot ulcers, tingling (pins and needles), burning ache, and loss of coordination/balance, leading to falls; all these occurring in a stocking-and-glove pattern.
Motor neuropathy: Involvement of motor nerves causes impairment of fine movements like opening bottles, buttoning up the shirt, typing, writing, climbing or descending stairs, problems in standing up from a seated position and so on so forth.
Autonomic neuropathy: Abdominal pain, vomiting, fecal incontinence (inability to control the evacuation of stools); cardiovascular involvement like increased heart rate, arrhythmias (a disturbance in the normal electrical conducting system of the heart), fainting (syncope); and urinary complications like urinary incontinence or poor urinary flow.

A Succinct Intro about Alpha-Lipoic Acid

Alpha-lipoic acid is a naturally occurring fatty acid synthesized in our body and present in a variety of foods but in a small quantity. These foods include spinach, broccoli, Brussel sprouts, potatoes, tomatoes, yeast, and red meat. Being a potent antioxidant, this fatty acid aids in defending against free-radical damage. Free radicals are highly reactive ions that induce oxidative damage throughout the body. Thus, α-lipoic acid has a potential to shield against the free-radical induced oxidative damage. Not to mention, this alpha-lipoic acid, sometimes also abbreviated as ALA, is not the same as alpha linoleic acid (an essential omega-3 fatty acid).

Mechanisms of Diabetic Neuropathy and their Relevance to ALA

Whilst most tissues require insulin for glucose uptake, the nerve cells, retina, and kidneys do not. Hence, the high blood glucose easily makes its way into the nerve cells. One of the chief mechanisms involved in the development of diabetic nerve damage is the polyol pathway (sorbitol-aldose reductase pathway). Aldose reductase is the enzyme, which catalyzes the conversion of glucose to sorbitol in tissues, including nerve cells (this reaction uses up NADPH). Since NADPH encourages the formation of reduced glutathione (3) and reduced glutathione (GSH) is a free-radical scavenger, ↓NADPH implies ↓ GSH and ↑ oxidative stress (free radicals are the major rascals that induce oxidative damage). There is an enzyme called sorbitol dehydrogenase, which is all set up in various tissues to convert sorbitol into fructose. Unfortunately, the dehydrogenase enzyme is missing/low in some tissues, including the nerve cells. The upshot is an accumulation of sorbitol, and as sorbitol is an osmotically active substance, it draws water into the nerve cells, destroying the protective sheath enclosing the Schwann cells (cells that ensheath the peripheral nerve fibers) terminating in nerve damage.

Another key fact extracted from scientific studies is that diabetic nerve cells show an upsurge in fructose levels. This fructose instigates the formation of more hazardous culprits, called advanced glycation end products (AGEs) (4). The formation of AGE products takes place when glucose binds to proteins.

The AGE products get deposited inside and around the peripheral nerves and further promote oxidative mutilation via:

Activating pro-inflammatory genes like nuclear factor kappa-B (NF-κB induces a programmed cell death of the nerve cells, called as apoptosis)
Contributing to the formation of hydrogen peroxide (other reactive oxygen species/free-radical that fosters chemical damage throughout the nerves)

All this plethora of events makes the nerve cells vulnerable to demyelination (loss of protective covering enclosing the nerves, i.e. myelin sheath), and peripheral neuropathy sets in.

With all the above description in mind, now let us turn our attention to the role of α-lipoic acid in diabetic neuropathy. Alpha-lipoic acid accentuates the GSH levels, and thereby not only defends against the oxidative damage brought on by hyperglycemia, yet ALA also has a potential in reducing the oxidized forms of other powerful antioxidants like vitamin C and vitamin E and rendering them more effective via transforming itself into dihydrolipoic acid (DHLA). Additionally, DHLA also reduces the ubiquinone (i.e. Coenzyme Q₁₀) from its oxidized form to the reduced form ubiquinol. An added bonus: CoQ₁₀ counteracts the nerve cell depletion, and investigations disclose that CoQ₁₀also increases the nerve conduction velocity, tone down the diabetic neuropathic pain, and pits its wits against peripheral neuropathy (5). Moreover, ALA suppresses the activation of NF-κB triggered by the AGE products. Therefore, the overall effect of ALA is a massively amplified antioxidant activity, which reverses the diabetic oxidative nerve damage, including an improvement in the sensory, motor, and autonomic functions (6).

The bottom line: ALA has several balls in the air to juggle with; nonetheless, none of them can beat it!

Recommended Dosage and Precautions

The dose of ALA recommended for diabetic neuropathy is 600-800 mg/day in divided doses (7).

Since ALA has a tendency to lower the blood glucose levels, take it under the supervision of your physician.

Conclusion

Given the above facts, what essentially hinder diabetics from making alpha-lipoic acid a component of their regular diet schedule and reaping its advantages? I guess nothing!