Accurate Education - Alpha Lipoic Acid (ALA)

Nutriceuticals:

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. It is a supplement with good evidence for benefit of use in neuropathic pain including peripheral neuropathy, low back pain and sciatica as well as the “brain fog” cognitive impairment associated with fibromyalgia.

The level of confidence (LOC) in the recommendation of ALA as an analgesic supplement is high.

See also:

Key to Links:

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Definitions and Terms Related to Pain

Terms:

Neuropathic Pain (“Nerve Pain”)

“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”)

Summary:

Lipoic acid is a compound produced by plants, animals, and humans. It has a dual role in the body as it is an antioxidant and a cofactor for various enzymes. It is synthesized by the body so it is. not a vitamin, but the quantities produced by the body are not enough to fulfill the energy requirement of cells. Thus, it must be obtained from the diet, especially from meat, vegetables, and fruits.

Lipoic acid has numerous clinically valuable properties and studies that support its use in diabetes and for reducing the risk for developing atherosclerosis, hypertension, heart failure, and myocardial infarction.

Bioavailability:

Relatively poor, but R-ALA is more bioavailable than standard formulations of ALA (racemic equal mixture of R-ALA and L-ALA. When commercially available, nano-formulations will likely be the preferred choice.

Food Sources:

In nature, the richest sources of ALA are animal tissues with high metabolic activity such as the heart, liver, and kidney. Among the vegetable sources, the highest ALA content is found in spinach followed by broccoli, tomatoes, peas, Brussels sprouts, and rice. However, dietary absorption from these sources is considered insufficient, not delivering substantial amounts of ALA into the blood.

Dose: 200 to 1800 mg/day

While there are no established guidelines for dosing with ALA, most studies demonstrating both safety and effectiveness used doses of 600 mg ALA, once or twice a day
Because standard ALA formulations contain equal amounts of R-ALA (active) and L-ALA (inactive), dosing of R-ALA would be equivalent in benefit to at least twice the dose of standard ALA.
ALA should be ingested on an empty stomach, at least 30 minutes before eating or at least 2 hours after eating
In order to maximize blood levels, take three 600-mg R-ALA doses (as NaR-ALA) at 15-minute intervals

Benefits:

Clinical trials have demonstrated that ALA is considered safe and well tolerated even at high doses and may be an effective therapy in improving the quality of life of patients affected by various disorders. There is a great deal of research supporting the following benefits. However, double blind, placebo studies remain lacking to establish definitive proof of these benefits.

ALA has anti-inflammatory properties that help with acute and chronic inflammation. Recent research indicates that the administration of ALA is associated with a significant reduction in systemic inflammation as well as oxidative stress, related to its function as a NRF2 activator.
ALA may reduce neuropathic pain symptoms in patients with sciatica) caused by disc-nerve root compression.
ALA may reduce the pain in osteoarthritis, especially in patients with type 2 diabetes.
With pain of unknown etiology, ALA can be effective regardless of the type of pain (arthralgia, neuropathic pain, and myalgia.
ALA is known as the “antioxidant of antioxidants.”
ALA has powerful inherent antioxidant effects acting as a free radical scavenger, but it also helps replenish other antioxidants including Vitamin C and Vitamin E, glutathione and CoQ10.
The benefits of ALA appear not to be limited solely to the symptoms of diabetic neuropathy. In fact, ALA can be considered as the only treatment that acts on the pathogenesis of some diseases, i.e. to prevent diabetic neuropathy. It has been shown to have beneficial effects on the regulation of insulin sensitivity and insulin secretion.
ALA has a strong protective effect on diabetic kidneys and oral ALA supplementation may be able to prevent early development and progression of diabetic kidney disease (nephropathy)
ALA is helpful in many diseases and conditions. ALA may: reduce diabetic polyneuropathy (DPN), diabetic peripheral neuropathy pain, promote weight reduction in obese patients and alleviate multiple sclerosis MS symptoms.
With migraine headaches, ALA decreases the attack frequency, number of headache days, and headache severity with supplemental 600 mg/day for three months
Evidence suggests ALA to be helpful in carpal tunnel syndrome (CTS) pain including reducing post-operative CTS surgery
ALA may help prevent the progression of kidney damage caused by oxidative stress.
ALA may also significantly decrease levels of triglycerides, total cholesterol, and low-density lipoproteins (LDLs – the “bad” cholesterol) but it will not affect levels of high-density lipoproteins (HDLs – the “good” cholesterol).ALA may have a positive effect on lowering both systolic and diastolic blood pressure
Evidence suggests ALA may be helpful in post-stroke recovery
ALA is useful in the treatment of burning mouth syndrome, a neuropathy-like condition linked to diabetes and poor glycemic control,
Therapy with the R-isomer form of ALA may reduce both the perceived intensity of the tinnitus and psychological distress in patients with cochlear dysfunction associated with metabolic syndrome. On the contrary, no significant positive effect has been shown with regard to tinnitus annoyance in patients with auditory nerve dysfunctions.

Forms:

ALA has two forms, R- and S- Lipoic Acid (R-ALA and S-ALA). Both are present equally in ALA supplements unless specified as R-Lipoic Acid. Only the natural R- form is present in foods while the S-form is synthetic (not found in nature) and is present only in supplements.

Special Considerations:

Lipoid Acid is, probably for most people, the best anti-oxidant supplement to take if only adding one
S-ALA, the synthetic form, may interfere with important functions of R-ALA
Recommended: R-ALA supplement (Na R-ALA) – Life Extension) over standard LA (depending on cost). When they become available, choose enhanced absorption formula (nano-based)
ALA liquid formulations have greater blood levels and bioavailability compared to solid ALA.
In rare cases in genetically predisposed individuals, ALA may trigger low blood sugar and should be discontinued

Alpha-Lipoic Acid (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, it plays a role in glucose metabolism, it boosts acetylcholine, a neurotransmitter that performs many brain functions especially memory and it reduces inflammation.

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 emotionally stressful conditions including chronic illness, chronic pain, obesity and addiction (see Antioxidants).

Sources of ALA

Although synthesized by the human body at low amounts, the ALA quantities produced are not enough to fulfill the energy requirement of the cell. Thus, it is mostly obtained from diet. ALA is found in red meat, kidney, liver, and heart of animals, while in plants it is found abundantly in spinach, tomatoes, broccoli, brussels sprouts, garden peas, potatoes, and rice bran but fruits are also a source.

Potential Benefits from Supplementing with Alpha Lipoic Acid (ALA):

Antioxidant

ALA is well established as a potent antioxidant. In addition to it’s own direct antioxidant activity, it has also been shown to 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’s benefits. Emerging evidences demonstrate that diabetes results from the excessive ROS generation and impairment of the antioxidant potential. ALA has been shown to improve glycemic control in diabetes and may offer protection against developing diabetes.

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)

Neuropathy, in particular Peripheral Neuropathy (PN), has no FDA-approved disease improvement therapy. The goal of PN clinical treatment is to relieve metabolic problems, repair nerves, reduce oxidative stress, and improve microcirculation and other clinical symptoms. The evidence supports the fact that ALA meets these goals.

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 impro
vement in pain.

Diabetes

In addition 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.

Brain Function

ALA is an ideal compound to treat brain and neural oxidative disorders involving free radical processes because it is a potent antioxidant that acts in the intracellular and extracellular environment, it regenerates other antioxidants such as vitamins C and E, and increase intracellular glutathione levels. (Glutathione is a vital intracellular and extracellular antioxidant that helps repair cells damaged by pollution, stress, and other harmful influences).

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 injury. 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 no nutritional value. Commercial supplements simply labelled “Alpha-Lipoic Acid” are a 50/50 “racemic” mixture of R-Alpha-Lipoic Acid and S-Alpha-Lipoic Acid, so, for example, a 600 mg tablet would actually only contain 300 mg 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. ALA should be ingested at least 2 hours after eating or at least 30 minutes before eating
.

While there are no established guidelines for dosing with ALA, most studies demonstrating both safety and effectiveness used doses of 600 mg ALA once or twice a day

For pain due to carpal tunnel syndrome:

Ac ombination 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 S-LA 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 is approximately twice as bioavailable 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.

Pregnancy

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.

Purchasing Supplements

When purchasing supplements reviewed on this web site and discussed with Dr. Ehlenberger, a discount on usual commercial pricing can be obtained by purchasing from Accurate Clinic’s online Supplement Store after acquiring the discount code from Accurate Clinic:

Accurate Clinic’s Supplement Store

or call Toll-Free: 877-846-7122 (Option 1)

References:

Alpha-Lipoic Acid – Overviews

Alpha-Lipoic Acid – Bioavailability (R-ALA vs L-ALA/racemic ALA)

Alpha-Lipoic Acid – Cognitive Impairment

Alpha-Lipoic Acid – Carpal Tunnel Syndrome

Alpha-Lipoic Acid – Diabetic Peripheral Neuropathy (DPN)

Alpha-Lipoic Acid & Epalrestat – Diabetic Peripheral Neuropathy (DPN)

Alpha-Lipoic Acid – Diabetes

Alpha-Lipoic Acid – Formulations

Alpha-Lipoic Acid – High Blood Pressure

Alpha-Lipoic Acid – Neuropathic Pain

Alpha-Lipoic Acid – with Superoxide Dismutase (S)D)

α-Lipoic Acid and Superoxide Dismutase in the Management of Chronic Neck Pain – 2014 No Highlights

Emphasis on Education

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

Should you wish more information regarding any of the subjects listed – or not listed – here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

For more information, please contact Accurate Clinic.

Supplements recommended by Dr. Ehlenberger may be purchased commercially online or at Accurate Clinic.

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Accurate Education – Alpha Lipoic Acid (ALA)

Nutriceuticals:

Alpha-Lipoic Acid (ALA)

Key to Links:

Alpha-Lipoic Acid (ALA)

Summary:

Sources of ALA

Potential Benefits from Supplementing with Alpha Lipoic Acid (ALA):

Purchasing Supplements

Accurate Clinic’s Supplement Store

References:

Alpha-Lipoic Acid – Overviews

Alpha-Lipoic Acid – Bioavailability (R-ALA vs L-ALA/racemic ALA)

Alpha-Lipoic Acid – Cognitive Impairment

Alpha-Lipoic Acid – Carpal Tunnel Syndrome

Alpha-Lipoic Acid – Diabetic Peripheral Neuropathy (DPN)

Alpha-Lipoic Acid & Epalrestat – Diabetic Peripheral Neuropathy (DPN)

Alpha-Lipoic Acid – Diabetes

Alpha-Lipoic Acid – Formulations

Alpha-Lipoic Acid – High Blood Pressure

Alpha-Lipoic Acid – Neuropathic Pain

Alpha-Lipoic Acid – with Superoxide Dismutase (S)D)

Emphasis on Education

For more information, please contact Accurate Clinic.

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