Alpha Lipoic Acid (ALA)
“Neuropathic” or nerve pain is pain initiated or caused by a primary lesion or dysfunction in a nerve or in the nervous system or pain arising as a direct consequence of a lesion or disease affecting the nervous system. Nerve pain is usually perceived as burning, electric, shock-like, tingling or sharp and may start at one location and shoot, or “radiate” to another location (like sciatica). Neuropathic pain can be “peripheral,” (outside the central nervous system),” like carpal tunnel pain or “central,” originating in the spinal cord or brain. Neuropathic pain is often a disease process, not simply the symptom of one.
For more information: Assessment and management of Neuropathic Pain
Alpha-Lipoic Acid (ALA)
(also called “Thioctic Acid”)
Alpha-Lipoic Acid (ALA) is an antioxidant manufactured in the body and present in certain foods including spinach and collard greens, broccoli, brewer’s yeast, beef and organ meats.
ALA offers multiple functions in the body. As an antioxidant, ALA protects our cells from damage due to free radicals, chemicals that are associated with oxidative stress that occurs during metabolism and dietary and environmental exposure and are implicated in the development of chronic diseases such as arteriosclerosis, heart disease, certain cancers and other age-related diseases. ALA also helps regenerate other antioxidants, plays a role in glucose metabolism, boostsing acetylcholine, a neurotransmitter that performs many brain functions, and reducing inflammation along with other proposed roles in maintaining good health.
A greater need for ALA may arise as part of aging as well as a means for combatting the increased oxidative stress that is associated with physical and emotional stressful conditions including chronic illness, chronic pain, obesity and addiction (see Antioxidants).
Potential Benefits from Supplementing with Alpha Lipoic Acid (ALA):
ALA is well established as a potent antioxidant. In addition to it’s own direct antioxidant, however, it has been shown to help replenish other antioxidants including Vitamins C and E, glutathione and Coenzyme Q10. There is also research that shows that ALA may be a NRF2 activator (see NRF2 Activators) which is a likely mechanism for some of ALA benefits.
Neuropathic Pain (NP – Nerve Pain – see Neuropathic Pain)
ALA has good evidence to support its benefit in reducing NP. Most of the research has been performed with diabetic peripheral neuropathy but there is also good evidence for ALA benefit for the pain associated with carpal tunnel syndrome.
Diabetic Peripheral Neuropathy (DPN)
There is excellent research evidence that demonstrates the benefit of ALA in the treatment of DPN. The benefits include reduced pain as well as improved nerve function as demonstrated by improvement of measured nerve conduction. ALA is believed to improve blood vessel function and blood flow to nerves as well a providing anti-inflammatory benefits to nerves.
A recent study demonstrated a significant reduction in stabbing and burning pain of the feet (but not with tingling sensation or numbness) within 1-5 weeks at a dose of 600mg ALA once daily. Pain was reduced 50% or greater after 3 weeks in 50 – 62% of patients treated with ALA.
ALA was very well tolerated: none of the patients with ALA 600mg/day discontinued the study, whereas with the higher doses 11% and 13% of patients dropped out because of adverse events during treatment with ALA 1200mg/day and ALA 1800mg/day, respectively. The most frequent adverse event was a dose-dependent increase in the incidence of nausea.
In an Italian study, treatment with a combination of ALA 600 mg and SOD 140 IU for 4 months led patients with diabetic neuropathy to experience a significant improvement in their electroneurographic testing and perception of pain. The best improvements were observed in sensory nerve conduction, thus confirming that a combination of two powerful antioxidant agents leads to improvement in both subjective and objective parameters in patients with diabetic neuropathy. (Comment: there is an apparent lack of commercial availablility of SOD in the U.S. However, many NRF2 activators (see NRF2 activators) have been shown to increase SOD activity and therefore they may offer an alternative means of gaining benefits assigned to SOD supplements).
Neck and Low Back Pain
A study recently published in 2014 evaluated the benefit of ALA with Superoxide Dismutase (SOD) in the treatment of chronic neck pain. Chronic neck pain (CNP) is often described as widespread hyperalgesia of the skin, ligaments, and muscles on palpation and on both passive and active movements in the neck and shoulder area, a description consistent with neuropathic pain.
Superoxide dismutase (SOD) is one of the most important antioxidant enzymes (see Superoxide dismutase (SOD), being responsible for neutralization of superoxide, the free radical occurring in the mitochondrial cellular respiration, the intracellular “energy production” of the cell. SOD has powerful anti-inflammatory benefits and there is good research demonstrating the role of SOD in chronic pain.
In an Italian study, a combination of ALA 600 mg and SOD 140 IU was given once daily to patients with chronic neck pain in combination with physical therapy that included transcutaneous electrical nerve stimulation (TENS), massage therapy, and functional rehabilitation. After 60 days of treatment, the ‘‘pain at rest’’ and “pain with movement” was significantly less in patients receiving ALA/SOD (81% of patients) with physical therapy compared with patients receiving physical therapy alone (29% of patients). Both groups reported improvements after the first month of treatment, but after 2 months, group 2 (who were treated with physical therapy alone) stopped improving, while patients in group 1 receiving ALA/SOD continued to experience improvement in their perceived pain.
A 2009 study evaluated the use of ALA (600mg/day) with gamma-linolenic acid (GLA), an omega 3 fatty acid (360mg/day), for sciatica pain associated with disc compression of nerve roots in the lower back. A six week course of therapy was associated with significant improvement in pain.
In additition to benefitting diabetic peripheral neuropathy (DPN). ALA may be helpful in treating another diabetes-related condition, autonomic neuropathy, a condition in which patients may experience palpitations and other symptoms related to the heart and blood pressure. ALA may also be helpful in lowering blood sugar as well.
One recent study individually assessed the effects of alpha lipoic acid (ALA), omega 3 fatty acid and vitamin E on insulin sensitivity (blood glucose and HbA1c) in patients with type 2 diabetes.The doses used in this study were: ALA 300 mg, omega 3 fatty acids Ecosapentaenoic acid 180 mg + Docosahexaenoic acid 120 mg and Vitamin E 400mg.
The results of this study showed that all three antioxidants alpha lipoic acid, omega 3 fatty acid and vitamin E decreased HbA1c with no side effects. Depending upon the cost benefit analysis vitamin E was the most cost effective even though the maximum improvement in blood glucose and HbA1c was with omega 3 fatty acid. But most importantly, combining these drugs might prove as an attractive option in patients with type 2 diabetes mellitus.
There is some research to support the benefit of ALA in improving brain function, possibly by increasing levels of acetylcholine. It may help protect brain and nerve tissue and offers potential for the treatment of stroke, dementia and improving cognitive functions including memory, recall, focus and concentration. Preliminary research suggests that ALA may be beneficial in post-traumatic brain injry. There may be a benefit as well for the cognitive impairment and “brain fog” associated with fibromyalgia, also thought to be related to mitochondrial function.
Forms of Alpha-Lipoic Acid (ALA)
Like many nutrients, ALA has two molecular forms that are chemically identical but are mirror images of one another, referred to as racemic forms: R-Alpha-Lipoic Acid (R-ALA) and S-Alpha-Lipoic Acid (S-ALA). R-ALA and S-ALA are referred to as “enantiomers” and a combination mixture of both is referred to as a “racemic” mixture. R-ALA is the natural, nutritionally active form found in the body and in food whereas S-ALA is chemically produced in the manufacture of R-ALA and has less, if any nutritional value. Commercial supplements simpley labelled “Alpha-Lipoic Acid” are a 50/50 “racemic” mixture of R-Alpha-Lipoic Acid and S-Alpha-Lipoic Acid, so, for example, a 600mg tablet would actually only contain 300mg of R-ALA.
Dosing of Alpha-Lipoic Acid (ALA)
Research that looks at uses of ALA often use the manufactured mixture of the combination R-ALA and S-ALA so if one supplements with R-ALA, the dosing would be half that of the combination form.
Taking Alpha-Lipoic Acid with a meal decreases bioavailability so it is recommend to take ALA on an empty stomach (1 hour before eating).
While there are no established guidelines for dosing with ALA, these are some suggested doses:
For cognitive benefits:
200-600 mg per day divided into two doses.
For diabetic neuropathy:
800 mg per day divided into two doses.
For antioxidant benefits:
50 – 100 mg per day divided into two doses.
For pain due to carpal tunnel syndrome:
Acombination of ALA-300mg, curcumin phytosome-500mg (see Meriva) and Vitamin B complex taken twice a day.
As recommended with starting any new medication or nutritional supplement: “Start Low, Go Slow.” Always begin with a low dose and slowly increase the dose as tolerated, based on effectiveness and, of course, your physician’s directions.
Choice of ALA Supplements
There is little evidence whether one ALA supplement is more effective than another. However, it is reported that R-LA and S-LA are combined because R-LA is highly unstable on its own and degenerates quickly so that pure R-ALA is not suitable for use in nutraceutical or pharmaceutical products. Rather, it should be treated as raw material for further processing into stable, bioavailable dosage forms.
Pharmacokinetic data reveals pure R-ALA is significantly less bioavailable than R-ALA found as a 50-percent component of racemic ALA (R-ALA + S-ALA); and R-ALA in a salt form is considerably more bioavailable than an equivalent dose of racemic ALA (R-ALA + S-ALA). This indicates SLA may function as a competitive inhibitor in the absorption of RLA.Thus, the sodium salt version of R-LA may be better absorbed than free lipoic acid, likely because of it higher solubility. One study did look at comparing the bioavailablility of R-ALA vs S-ALA and R-ALA has approximately twice the bioavaillability as S-ALA meaning better absorption.
The take home message:
There may be arguments that one form of ALA supplement has advantages over another – research is incomplete. If one form of supplement is ineffective or associated with side effects, it would make sense to try another form before giving up. Remember to “Start Low, Go Slow.”
Side effects ALA
Side effects for using Alpha-Lipoic Acid as a supplement are generally rare but may include diarrhea, fatigue, insomnia and skin rash.
Synergistic Benefits of Combining with other Supplements
There is theoretical and research evidence that the combining of ALA with other supplements may provide a synergistic benefit, where the benefits of a combination would be greater than the individual supplements on their own. In a study on ALA and carpal tunnel syndrome, a combination of ALA-300mg, curcumin phytosome-500mg (see Meriva) and Vitamin B complex taken twice a day proved very effective in reducing pain.
Acetyl-L-Carnitine (see Acetyl-L-Carnitine), another antioxidant, has been studied in combination with ALA and this combination appears effective in treating neuropathic pain.
Omega-3 fatty acids, including linolenic acid, are also sometimes combined with ALA due to their potent anti-inflammatory benefits.
Possible Drug Interactions with ALA
If you are currently being treated with any of the following medications, you should not use alpha-lipoic acid without first talking to your health care provider.
Medications for diabetes — Apha-lipoic acid can combine with these drugs to lower blood sugar levels, raising the risk of hypoglycemia or low blood sugar. Ask your health care provider before taking alpha-lipoic acid, and watch your blood sugar levels closely. Your health care provider may need to adjust your medication doses.
Chemotherapy medications — Alpha lipoic acid may interfere with some chemotherapy medications used in the treatment of cancer. Always ask your oncologist before taking any herb or supplement, including alpha-lipoic acid.
Thyroid medications, Levothyroxine — Apha-lipoic acid may lower levels of thyroid hormone. Your health care provider should monitor blood hormone levels and thyroid function tests closely.
Alpha-lipoic acid hasn’t been studied in pregnant or breastfeeding women, so researchers don’t know if it’s safe. If you wish to get the benefits of ALA with these conditions, eat plenty of the foods rich in ALA as noted above.
Alpha-Lipoic Acid – Overviews
- Alpha-lipoic acid as a dietary supplement – Molecular mechanisms and therapeutic potential – 2008
- Lipoic acid – biological activity and therapeutic potential – 2011
Alpha-Lipoic Acid – Bioavailability
- Age and gender dependent bioavailability of R- and R,S-α-lipoic acid – A pilot study – 2012
- Single dose bioavailability and pharmacokinetic study of a innovative formulation of α-lipoic acid (ALA600) in healthy volunteers – 2011
Alpha-Lipoic Acid – Cognitive Impairment
- Trial of Omega-3 Fatty Acids and Alpha Lipoic Acid in Alzheimer’s Disease
- A Randomized Placebo-Controlled Pilot Trial of Omega-3 Fatty Acids and Alpha Lipoic Acid in Alzheimer’s Disease
- Lipoic Acid Treatment after Brain Injury – Study of the Glial Reaction
Alpha-Lipoic Acid – Carpal Tunnel Syndrome
- Clinical Usefulness of Oral Supplementation with Alpha-Lipoic Acid, Curcumin Phytosome, and B-Group Vitamins in Patients with Carpal Tunnel Syndrome Undergoing Surgical Treatment
- Treatment of carpal tunnel syndrome with alpha-lipoic acid. – PubMed – NCBI
Alpha-Lipoic Acid – Diabetic Peripheral Neuropathy (DPN)
- A systematic review and meta-analysis of a-lipoic acid in the treatment of diabetic peripheral neuropathy
- Combination of Alpha Lipoic Acid and Superoxide Dismutase Leads to Physiological and Symptomatic Improvements in Diabetic Neuropathy – 2012
- Efficacy and safety of alpha-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathy – 2007
- Oral Treatment With Alpha-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy – 2006
- Thioctic acid for patients with symptomatic… [Treat Endocrinol. 2004] – PubMed – NCBI
- Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study) – 1995
- Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid- a meta-analysis – 2004
Alpha-Lipoic Acid – Diabetes
- A Comparative Study of Effects of Omega-3 Fatty Acids, Alpha Lipoic Acid and Vitamin E in Type 2 Diabetes Mellitus
Alpha-Lipoic Acid – Formulations
- Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms – 2014
- The plasma pharmacokinetics of R-(+)-lipoic acid administered as sodium R-(+)-lipoate to healthy human subjects – 2007
Alpha-Lipoic Acid – Neuropathic Pain
- Possible role of alpha-lipoic acid in the treatment of peripheral nerve injuries – 2010
- The use of alpha-lipoic acid (ALA), gamma linolenic acid (GLA) and rehabilitation in the treatment of back pain: effect on health-related quality o… – PubMed – NCBI
- Thioctic acid and acetyl-L-carnitine in the treatment of sciatic pain caused by a herniated disc: a randomized, double-blind, comparative study. – PubMed – NCBI
Alpha-Lipoic Acid – with Superoxide Dismutase (S)D)
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