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Alpha-Lipoic Acid

Alpha-lipoic acid (ALA) is a mitochondrial compound involved in energy metabolism. It is commonly taken with L-Carnitine supplements, as they are related in mechanisms. ALA provides a short but potent reduction of oxidation by increasing anti-oxidant enzymes, and may decrease blood glucose acutely.

Our evidence-based analysis on alpha-lipoic acid features 156 unique references to scientific papers.

Kamal Patel
Research analysis led by and reviewed by the Examine team.
Last Updated:

Summary of Alpha-Lipoic Acid

Primary information, health benefits, side effects, usage, and other important details

Alpha-Lipoic Acid (ALA) is a mitochondrial compound that is highly involved in energy metabolism. It is synthesized in the body and can be consumed through eating meat. It is also minimally present in some fruits and vegetables.

In supplement form, it has shown benefit for various forms of oxidation and inflammation. These effects protect against heart diseases, liver diseases, diabetes, and neurological decline associated with aging.

ALA is a potent anti-oxidant compound. It works with mitochondria and the body's natural anti-oxidant defenses. ALA is also seen as an anti-aging compound since it can reverse some of the oxidant damage related to the effects of aging.

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How to Take

Recommended dosage, active amounts, other details

Standard dosages of Alpha-Lipoic Acid (ALA) tend to be in the range of 300-600mg, with little differentiation based on whether the racemic mixture of ALA (S- and R- isomers) or Na-R-ALA results in higher blood levels.

ALA appears to be absorbed via transporter-related means, and despite being inherently fat-soluble it does not require dietary fatty acids to be absorbed from the gut. ALA supplementation can be taken in a fasted state.

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Human Effect Matrix

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The Human Effect Matrix summarizes human studies to tell you what effects Alpha-Lipoic Acid has on your body, how much evidence there is, and how strong these effects are.

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Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b
Symptoms of Diabetic Neuropathy
Notable Very High See 2 studies
Not yet compared to reference drugs, but it has been subject to a meta-analysis and appears to be more effective than other options for reducing nerve pain associated with diabetes. The lack of a reference comparison and some evidence suggesting no effect prevent a strong rating.
grade-b
General Oxidation
Minor High See all 6 studies
Appears to reduce biomarkers of oxidation
grade-b
Blood Pressure
- Very High See all 6 studies
The majority of evidence using intravenous or oral supplements fail to find an influence, and the one study to suggest a reduction was also confounded with weight loss (known to reduce blood pressure). It can be assumed that ALA has no significant influence on blood pressure even in studies where blood flow is altered
grade-c
Symptoms of Intermittent Claudication
Notable - See study
The reduction of claudication symptoms appears to be fairly potent with ALA supplementation, although there is not a large body of evidence overall.
grade-c
Blood Flow
Minor Very High See 2 studies
May increase blood flow, although not the a remarkable degree. Possibly secondary to antioxidative effects
grade-c
HbA1c
Minor Moderate See all 3 studies
There appears to be a slight reducing effect on HbA1c
grade-c
Inflammation
Minor Moderate See 2 studies
Mixed effects depending on what inflammatory biomarker or cytokine is measured; practical significance unknown
grade-c
Lipid Peroxidation
Minor Very High See 2 studies
Appears to reduce biomarkers of lipid peroxidation (MDA mostly)
grade-c
Nerve Repair
Minor - See study
May increase nerve regeneration rates and be of aid to nervous system injury
grade-c
Protein Carbonyl Content
Minor - See study
Appears to reduce protein carbonylation, which may be related to the antioxidative effects
grade-c
Weight
Minor Moderate See all 4 studies
It is possible that high doses (1,800mg) may have a body weight reducing effect in obese persons, but this requires more evidence.
grade-c
Anti-Oxidant Enzyme Profile
- - See 2 studies
Mixed effects on antioxidant enzymes, with decreases in glutathione peroxidase and increases in catalase with no effect on SOD
grade-c
Blood Glucose
- See study
A small decrease in blood glucose is noted with oral supplementation of ALA, related to the glucose disposal properties
grade-c
C-Reactive Protein (CRP)
- Moderate See 2 studies
Although there may be a reduction of C-Reactive protein in some populations, for the most part ALA does not seem significantly effective in reducing this inflammatory biomarker of cardiovascular disease
grade-c
Heart Rate
- - See study
No significant interaction between ALA and heart rate has been noted
grade-c
Insulin Sensitivity
- - See study
No significant influence on insulin sensitivity has been noted
grade-c
Motion Sickness
- - See study
Insufficient evidence to support a reduction in motion sickness with ALA supplementation
grade-c
Symptoms of Rheumatoid Arthritis
- - See study
No significant interaction between ALA supplementation and symptoms of rheumatoid arthritis
grade-c
Treatment of Dementia
- - See study
No significant rehabilitative effect of ALA on cognitive decline has been noted
grade-d
Muscle Creatine Content
Minor - See study
Has been associated with augmenting creatine uptake into muscle cells acutely; long term influence unknown
grade-d
Oxidation of LDL
Minor - See study
Appeared to increase oxidation of LDL according to one study, which was abolished by exercise but noted to be a concern during rest.
grade-d
Glycemic Control
- - See study
No significant practical benefit on glycemic control noted

Studies Excluded from Consideration

  • Excluded due to being intravenous injections and not oral supplementation[1]

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Things to Note

Is a Form Of

Primary Function:

Other Functions:

Also Known As

ALA, thioctic acid, 1, 2-dithiolane-3-pentanoic acid, ala, Tiolepta

Do Not Confuse With

Alpha-Linolenic Acid (omega-3 fatty acid)

Goes Well With

Caution Notice

Warning: potential for Severe Adverse Events (SAEs). Although ALA has been well-studied and found to be safe at standard doses in humans (typically 300-600mg), high doses are toxic and may be fatal. Consult with your personal physician before taking any supplement, and do not exceed recommended doses.

  • Alpha-lipoic acid appears to be water soluble in the gut and is absorbed by transporters. Coingestion with fatty acids in the diet does not appear to be required.

  • Can be bound by avidin, and thus coingestion with raw egg whites can possibly negate the benefits of supplementation. -One study has indicated that long-term, relatively high-dose ALA treatment is liver toxic in mice.

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Research Breakdown on Alpha-Lipoic Acid

1Sources and Synthesis

1.1Sources

1.2Biosynthesis

1.3Structure and Stability

2Pharmacology

2.1Absorption

2.2Serum

2.3Metabolism

2.4Elimination

2.5Metal Chelation

3Life Extension and Longevity

3.1Mechanisms

3.2Animal Interventions

4Neurology and the Brain

4.1Appetite

4.2Mechanisms

4.3Glutaminergic Neurotransmission

4.4Cholinergic Neurotransmission

4.5Dopaminergic Neurotransmission

4.6Serotonergic Signaling

4.7Adrenergic (Adrenaline) Signaling

4.8Oxidation

5Nerve function

5.1General

5.2Carpal Tunnel Syndrome

5.3Diabetic Neuropathy

6Interactions with the Liver

6.1Mechanisms

7Interactions with Obesity and Body Fat

7.1Mechanisms

7.2Energy Expenditure

7.3Interventions

8Interactions with Skeletal Muscle

8.1Mechanisms

8.2Glucose Uptake

9Interactions with Cardiac Health

9.1Platelet Function

9.2Endothelium

9.3Triglycerides and Lipoproteins

10Interactions with Glucose Metabolism

10.1Insulin

10.2Usage in Diabetes

11Interactions with Oxidation

11.1Mechanisms

11.2Interventions

12Inflammation and Immunology

12.1Mechanisms

12.2Rheumatoid Arthritis

13Interactions with Hormones

13.1Leptin

14Nutrient-Nutrient Interactions

14.1L-Carnitine

14.2Sesamin

14.3Avidin

15Toxicity and Safety

15.1General

15.2Interventions
Click here to see all 156 references.

This page is regularly updated, to include the most recently available clinical trial evidence.

Each member of our research team is required to have no conflicts of interest, including with supplement manufacturers, food companies, and industry funders. The team includes nutrition researchers, registered dietitians, physicians, and pharmacists. We have a strict editorial process.

This page features 156 references. All factual claims are followed by specifically-applicable references. Click here to see the full set of research information and references for Alpha-Lipoic Acid.

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