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Alpha-lipoic acid

  • Dietary supplement
  • Varies by country
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Alpha-lipoic acid does in the body

Taken for nerve pain in diabetes, for blood sugar, and as a general antioxidant

Lipoic acid is a small sulphur-containing molecule that your mitochondria make and then permanently attach to a handful of enzymes, where it acts as a swinging arm passing chemical groups between reaction sites. Crucially, the lipoic acid in a capsule does not get attached to those enzymes — the attachment happens during enzyme assembly, from lipoic acid made inside the mitochondrion. What a supplement provides is free lipoic acid circulating in the body, which is a reactive sulphur compound that can be reduced and re-oxidised. That is a genuine chemistry, and it is not the chemistry the molecule is famous for.

What happened in people

Five weeks of oral alpha-lipoic acid reduced diabetic neuropathy Total Symptom Score by 48 to 52% against 32% on placebo

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.

The limit that matters most

That supplemental lipoic acid supports the mitochondrial enzymes whose cofactor it is named for, which it does not join

Where it acts
Absorbed in the small intestine and distributed widely; endogenous lipoyl groups are covalently bound to mitochondrial dehydrogenase complexes, which supplemental lipoic acid does not join
Kind of result
Symptoms and quality of life
Supervision
Not usually supervised: sold as a supplement or food ingredient where recorded. That is a legal category, not a safety judgement.

What the registries record it as

  • The supplement label database classes it as non-nutrient/non-botanical, under the name Alpha Lipoic Acid.

    NIH Dietary Supplement Label Database · 8 · read 2026-08-29

  • 5 registered substances share the start of this name, which is why a search for it can return more than one thing.

    FDA substance registry · 73Y7P0K73Y · read 2026-08-29

Where each sentence above came from

No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.

Shown as the opening line on this page.

A limit recorded against this substance. Not signed off as a reviewed claim.

The four opening statements run to 136 words.

Words this page uses

Four words worth knowing first

Chosen from what this page shows, with each one explained before the word it depends on.

Stand-in result

A stand-in result is a number measured because the real result takes too long.

A picture of it, and where the picture fails

It is like judging a journey by the speedometer rather than by arriving.

Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.

What people get wrong. A stand-in result is often reported as the result itself.

A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.

Randomisation

Randomisation means chance decides who gets which treatment.

A picture of it, and where the picture fails

It is like a coin toss deciding the groups.

Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.

What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.

Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.

Confidence interval

A confidence interval is the range the true answer is likely to sit in.

A picture of it, and where the picture fails

It is like a weather forecast giving a range rather than one number.

Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.

What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.

An interval estimate that would contain the true parameter in a stated proportion of repeated studies.

Pathway

A pathway is a chain of steps inside a cell, each one setting off the next.

A picture of it, and where the picture fails

A pathway is like a row of dominoes.

Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.

What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.

An ordered series of molecular interactions producing a defined cellular change.

What happened in peopleRead from sources, not yet reviewed

What was measured, goal by goal

One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.

Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.

There is no single score. A strong test result and a weak life result are different facts.

Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
GoalLife outcomeWhat a body can doHow a person feelsA test resultA step in the bodyHarmsHow longWho was studied
Blood sugarNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Nothing in the sources checkedNo registered study lists a symptom measure for this goal.Only a number moved2 registered test measure.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
Body weightNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Nothing in the sources checkedNo registered study lists a symptom measure for this goal.Only a number moved1 registered test measure.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
EnergyNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Waiting for a reviewer1 registered symptom measure.Nothing in the sources checkedNo registered study lists a test result for this goal.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
Healthy ageingWaiting for a reviewer1 registered study measure of this kind. No reviewed result yet.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Nothing in the sources checkedNo registered study lists a symptom measure for this goal.Nothing in the sources checkedNo registered study lists a test result for this goal.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
Fertility and sexual healthNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Nothing in the sources checkedNo registered study lists a symptom measure for this goal.Nothing in the sources checkedNo registered study lists a test result for this goal.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Blood sugar
insulin resistance; insulin sensitivity
Body weight
body weight
Energy
fatigue severity scale
Healthy ageing
mortality
Fertility and sexual health
good quality blastocyst per fertilized oocyte on day 5

Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.

What each mark on this table means
Nothing in the sources checked
No registered study lists a life outcome for this goal.
Only a number moved
2 registered test measure.
Not recorded
Harms were not a registered measure for this goal.
Waiting for a reviewer
Who was studied is listed further down the page.

What happened in peopleRead from sources, not yet reviewed

What happened in people

Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.

Change from baseline in Total Symptom Score

The study showed what it set out to show

Who was studied
SYDNEY 2 — oral alpha-lipoic acid in symptomatic diabetic polyneuropathy
How many people
181
Study design
Multicentre randomised double-blind placebo-controlled dose-ranging, 5 weeks
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
TSS reduced 51% at 600 mg, 48% at 1,200 mg, 52% at 1,800 mg versus 32% on placebo, all P < 0.05; response rates 62%, 50%, 56% versus 26%
Repeated elsewhere
Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. Three doses across a threefold range produced essentially identical effects, which is not a dose-response. The Neuropathy Impairment Score, the objective measure, was only numerically reduced. Five weeks is short for a chronic progressive condition.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral capsule or tablet, as racemic alpha-lipoic acid or as R-lipoic acid

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

Composite of Neuropathy Impairment Score lower limbs plus seven neurophysiologic tests

The study did not show it

Who was studied
NATHAN 1 — alpha-lipoic acid over four years in diabetic polyneuropathy
How many people
460
Study design
Multicentre randomised double-blind parallel-group, 4 years
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
No significant difference in the primary composite, P = 0.105; secondaries NIS P = 0.028, NIS-LL P = 0.05, NIS-LL muscular weakness P = 0.045
Repeated elsewhere
Failed to Replicate

What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.

The limits of this study, and where it came from

Main limit. Serious adverse events were higher on alpha-lipoic acid at 38.1% than on placebo at 28.0%. Nerve conduction and quantitative sensory tests did not significantly worsen on placebo, so the trial had little deterioration to slow.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral capsule or tablet, as racemic alpha-lipoic acid or as R-lipoic acid

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

Mean difference in body weight and BMI versus placebo

The study showed what it set out to show

Who was studied
Kucukgoncu 2017 meta-analysis of alpha-lipoic acid for weight loss
How many people
10
Study design
Meta-analysis of 10 randomised double-blind placebo-controlled studies
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Weight -1.27 kg (95% CI 0.25 to 2.29); BMI -0.43 kg/m2 (95% CI -0.82 to -0.03)
Repeated elsewhere
Partially Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. Meta-regression found no effect of dose on either outcome. A weight effect without a dose-response is hard to attribute to the compound. Sample size counts studies, not participants.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral capsule or tablet, as racemic alpha-lipoic acid or as R-lipoic acid

Interval reported. 95% CI 0

Written into the record, not signed off as a reviewed claim.

Renal biopsy findings and proteinuria after lipoic acid supplementation

The study did not show it

Who was studied
Spain 2021 — NELL1-associated membranous nephropathy after lipoic acid
How many people
5
Study design
Case series arising from a clinical trial treatment arm
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Four biopsy-proven and one suspected case of NELL1-associated membranous nephropathy; remission after discontinuation and supportive therapy
Repeated elsewhere
Unreplicated

What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.

The limits of this study, and where it came from

Main limit. High-grade proteinuria was an unexpected adverse event specific to the treatment arm of a multiple sclerosis trial. Five cases support no incidence estimate, and nobody had been monitoring urinary protein in lipoic acid users.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral capsule or tablet, as racemic alpha-lipoic acid or as R-lipoic acid

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

What we know
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.

What happened in peopleRead from sources, not yet reviewed

How close this is to real life

The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.

  1. Living longer, or avoiding a major event Evidence recorded. Death, a heart attack, a stroke, a hospital stay.1 registered measure of this kind. No reviewed result.
  2. What a body can do day to day Evidence recorded. Walking, dressing, breathing, recovering.5 registered measures of this kind.
  3. Measured performance Evidence recorded. How much was lifted, how far was run, how fast.5 registered measures of this kind.
  4. Symptoms and quality of life Evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.2 registered measures of this kind.
  5. A number that stands in for health Evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.8 registered measures of this kind.
  6. A step measured inside a person Evidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
  7. Animals Evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in C. elegans (roundworm), Drosophila (fruit fly), Mouse, Rat. A result in animals says what to test next. It does not say what happens in people.
  8. Cells in a dish Evidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
  9. A guess from software No evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.

Higher on these steps means closer to something a person would feel. It does not mean better done.

What it changes in the bodyRead from sources, not yet reviewed

The path through the body

From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.

  1. Start

    Alpha-lipoic acid

    What a person takes: Oral capsule or tablet, as racemic alpha-lipoic acid or as R-lipoic acid.

    The measurement behind this step

    Sold in the United States as a dietary supplement under DSHEA with no pre-market review, and licensed as a prescription medicine for symptomatic diabetic polyneuropathy in Germany and several other countries — the same molecule under two regulatory regimes. Nearly all trial material is racemic; the naturally occurring enantiomer is R-lipoic acid, and products sold as pure R-lipoic acid are not the material the trials used. Free lipoic acid polymerises on exposure to heat and light, so storage conditions affect what is actually in a capsule. Absorption is reduced by food and the plasma half-life is on the order of tens of minutes.

  2. Getting in

    Absorbed fast, cleared fast

    Lipoic acid is taken up quickly from the gut and disappears from the blood within about an hour, which is why trials give it once or twice daily at large doses.

    Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.

    The measurement behind this step

    Oral bioavailability is modest and reduced by food, with a plasma half-life on the order of tens of minutes and rapid beta-oxidation to bisnorlipoate and tetranorlipoate. The very short exposure window is a genuine pharmacological constraint and is rarely mentioned alongside claims about sustained antioxidant protection.

  3. Reaching the cell

    It is reduced inside cells to a two-thiol form

    Once inside cells, the ring in lipoic acid is opened to give two free sulphur groups. That reduced form is the chemically active species.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Lipoic acid is reduced to dihydrolipoic acid by lipoamide dehydrogenase, glutathione reductase and thioredoxin reductase. Dihydrolipoic acid is a strong reductant that can regenerate ascorbate and glutathione and chelate transition metals — the properties that support the antioxidant framing, and which apply to the free molecule rather than to the bound cofactor.

  4. What it acts on

    What it does not do is join the enzyme complexes

    The famous role of lipoic acid is as a permanently attached arm on mitochondrial enzymes. That attachment happens inside the mitochondrion during assembly, using lipoic acid the cell makes itself.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Lipoyl synthase installs the sulphurs onto an octanoyl group already amide-linked to the E2 lysine, so the cofactor is made in place rather than captured from the pool. Mammalian cells do not efficiently ligate exogenous free lipoate onto pyruvate dehydrogenase or alpha-ketoglutarate dehydrogenase. The supplement and the cofactor share a name and a structure and not a job.

  5. The change it makes

    The measured clinical effect is on how neuropathy feels

    Over five weeks, symptom scores for stabbing pain, burning, tingling and numbness fell by about half, against about a third on placebo.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    SYDNEY 2 recorded Total Symptom Score reductions of 51%, 48% and 52% at 600, 1,200 and 1,800 mg against 32% on placebo, with response rates of 62%, 50% and 56% against 26%. Three doses spanning a threefold range produced indistinguishable effects, which is not the profile of a dose-dependent pharmacological action.

  6. What that does for a person

    Over four years, the objective composite did not move, and harms rose

    The long trial measuring actual nerve function found no significant difference. Serious adverse events were more common on lipoic acid than on placebo.

    Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.

    The measurement behind this step

    NATHAN 1 primary composite P = 0.105 over four years in 460 patients, with several impairment secondaries favouring treatment. Serious adverse events occurred in 38.1% on alpha-lipoic acid against 28.0% on placebo. Separately, five cases of NELL1-associated membranous nephropathy were traced to lipoic acid supplementation, with remission on discontinuation.

No suggested links are held for this record, so nothing is hidden from this path.

What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.

What it would be like to takeRead from sources, not yet reviewed

Felt, measured, or meaningful

Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.

Felt

Things a person could notice without a test.

  • fatigue severity scale
  • appetite suppression

Measured

Things only a test, a scale or a device shows.

  • aim 1 change in flow mediated dilation
  • insulin resistance
  • insulin sensitivity
  • body weight
  • acute change in flow mediated dilation
  • chronic change in flow mediated dilation
  • acute change in exercise capacity
  • chronic change in exercise capacity
  • flow mediated dilation
  • 24 hour blood pressure

Meaningful

Things that change how a life goes, not only a number.

  • activities of daily living at 18 months
  • mortality
  • mobility timed 25 foot walk
  • functional independence

A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.

Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.

Measured, but not felt. A number moves. The person notices nothing. Both can be true.

Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.

Matters, but takes years. The result that counts may take longer than anyone would keep watching.

Names that fit none of the three (24)
  • f2 isoprostane
  • ototoxicity measurement
  • forearm blood flow
  • biomarkers of oxidative stress
  • endothelial function
  • brain atrophy by mri
  • spirometric fvc values at baseline
  • spirometric fvc values at endpoint
  • spirometric fev1 values at baseline
  • spirometric fev1 values at endpoint
  • spirometric fef values at baseline
  • spirometric fef values at endpoint
  • histological evaluation
  • trails making test part b
  • ventilator free days
  • total symptoms
  • phase i percentage of adverse events
  • cycles in six months of therapy
  • good quality blastocyst per fertilized oocyte on day 5
  • comparison of oral tolerance between r la and racemic la

These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.

What it would be like to takeRead from sources, not yet reviewed

How long anything takes

Nine different lengths of time that get confused with each other. None of them is worked out from another.

  1. Before anything is noticed. RNAWiki does not store this separately, and never works it out from another figure on this page.

  2. Before a test result moves. RNAWiki does not store this separately, and never works it out from another figure on this page.

  3. Before performance moves. RNAWiki does not store this separately, and never works it out from another figure on this page.

  4. How long the result was watched. No finished study window is recorded for a study that tested this substance.

  5. How long people took it. How long people actually took it is not stored. The study window is not the same thing.

  6. How long people were followed. Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.

  7. How fast the body clears it. 0.5 hours hours

    Read from the label, which states: “The decline observed in the plasma concentration was steep (t1/2, 0.5 h).”

  8. How long effects linger. RNAWiki does not store this separately, and never works it out from another figure on this page.

  9. Beyond the studies. Nothing is recorded about the long term.

    The longest finished study sets the edge of what anyone measured.

A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.

What is missing or unclearRead from sources, not yet reviewed

Were people like you studied?

RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.

Who was studied

People similar to this profile were included.

  • People with diabetic neuropathy, particularly in Germany where it is prescribed, people taking it for blood glucose or weight, and a general antioxidant market.

Who is missing from the studies

  • Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

Where the result stopped carrying

  • The four-year disease-modification endpoint in diabetic polyneuropathy, missed at P = 0.105
  • The assumption that this compound has no serious harms, which a nephrology case series overturned in 2021
  • This is a scope explorer, not a diagnosis engine.
  • It shows who was studied so you can see whether people similar to you were included.

RNAWiki cannot tell whether a study fits you. It can show who was in it.

What it would be like to takeRead from sources, not yet reviewed

Why it might seem to do nothing

A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.

It was studied for a different goal

The studies measured something else entirely.

On this record: Some registered studies measured things that match no goal on this page.

It was studied in different people

The people in the studies were not much like the reader.

On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

The evidence may simply be wrong

Small early studies often do not hold up.

On this record: RNAWiki has not yet published a reviewed conclusion for this use.

The product may not be what it says

Contents of a sold product are not always what the label states.

On this record: This is sold as a supplement, so no agency checked what is in a given tub before it was sold.

Other reasons RNAWiki checked and found nothing for (9)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.

None of these is a reason to take more. Taking more is not a step this page ever suggests.

What it would be like to takeRead from sources, not yet reviewed

What taking it involves

The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.

How it is supplied

Varies by country

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Read from the recorded approval status.

No source is stored against this line.

Form and route

Oral capsule or tablet, as racemic alpha-lipoic acid or as R-lipoic acid

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form and route recorded on this substance.

No source is stored against this line.

Who oversees it

Not usually supervised: sold as a supplement or food ingredient where recorded. That is a legal category, not a safety judgement.

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

The identity record classes it as a supplement ingredient; no medicines register records an approval.

No source is stored against this line.

What is in the pack

Sold in the United States as a dietary supplement under DSHEA with no pre-market review, and licensed as a prescription medicine for symptomatic diabetic polyneuropathy in Germany and several other countries — the same molecule under two regulatory regimes.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on how this is sold. The rest of the recorded wording: Nearly all trial material is racemic; the naturally occurring enantiomer is R-lipoic acid, and products sold as pure R-lipoic acid are not the material the trials used. Free lipoic acid polymerises on exposure to heat and light, so storage conditions affect what is actually in a capsule. Absorption is reduced by food and the plasma half-life is on the order of tens of minutes.

No source is stored against this line.

Where it is registered

Regulatory records are listed in the technical disclosure at the foot of this page.

Counted from records

Where this came from

A count of rows RNAWiki holds. It describes our records, not your body.

Register entries are stored per jurisdiction and shown with their dates.

No source is stored against this line.

Why people stop

Not recorded.

Nothing recorded

Where this came from

RNAWiki holds nothing here and says so rather than guessing.

No record of why people stopped taking it is stored for this substance.

No source is stored against this line.

What it would be like to takeRead from sources, not yet reviewed

What can go wrong

Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.

Worth asking a clinician aboutWritten into the record from the studies named on this page

Nausea, rash and, at high doses, hypoglycaemia are the commonly reported effects, and the compound is insulin-mimetic enough that people on glucose-lowering therapy should be aware of it. Over four years, serious adverse events occurred in 38.1% of treated patients against 28.0% on placebo, which is the most consequential safety figure in this literature and comes from the trial that missed its primary endpoint. Five cases of NELL1-associated membranous nephropathy, four biopsy-proven, have been traced to lipoic acid supplementation, presenting with high-grade proteinuria and remitting on discontinuation. Alpha-lipoic acid is also one of only two medications — the other being methimazole — that a 2020 review of insulin autoimmune syndrome classifies as having a high-strength association with triggering that condition, in which autoantibodies to endogenous insulin cause recurrent hypoglycaemia; the same review notes the association has been increasing over the last decade and that the originally proposed HLA-DRB1*0406 restriction was not confirmed in Caucasians or in other Asian populations.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

Reports sent to a regulator

  • These are reports people sent to a regulator. They do not show the medicine caused the reaction.
  • Nobody counted how many people took the medicine and reported nothing.
  • The same event can be reported more than once, and many reports are incomplete.
  • News coverage, lawsuits and new warnings change how often people report.
  • A count is not a rate and not a risk.

Alpha-lipoic acid appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 55 reaction mentions were counted. One report can name several reactions.

The recorded terms (10)
  • drug-induced liver injury — 8 reaction mentions
  • hepatotoxicity — 8 reaction mentions
  • hepatic cirrhosis — 7 reaction mentions
  • hepatic encephalopathy — 7 reaction mentions
  • hepatic necrosis — 7 reaction mentions
  • drug interaction — 6 reaction mentions
  • areflexia — 3 reaction mentions
  • diabetic neuropathy — 3 reaction mentions
  • glycosylated haemoglobin increased — 3 reaction mentions
  • muscle contractions involuntary — 3 reaction mentions
  • open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot

Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.

Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

What is missing or unclearRead from sources, not yet reviewed

Does the exact form matter?

Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.

The form that was studied

Oral capsule or tablet, as racemic alpha-lipoic acid or as R-lipoic acid

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form used in the studies cited on this page.

No source is stored against this line.

What is sold

Nearly all trial material is racemic; the naturally occurring enantiomer is R-lipoic acid, and products sold as pure R-lipoic acid are not the material the trials used. Free lipoic acid polymerises on exposure to heat and light, so storage conditions affect what is actually in a capsule. Absorption is reduced by food and the plasma half-life is on the order of tens of minutes.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on which forms are sold and how they compare.

No source is stored against this line.

What is recorded as being sold

  • 48 products list this as an active ingredient in the United States drug directory. 11 of them contain it and nothing else.

    FDA National Drug Code directory · 0642-0207 · read 2026-08-29

  • They are sold as liquid, ointment, pellet, powder, solution/ drops and spray, taken oral and topical.

    FDA National Drug Code directory · 0642-0207 · read 2026-08-29

  • 36 published labels name it as an active ingredient. None of them describes this substance alone, so no label text on this page can be attributed to it rather than to a combination.

    US prescribing information · 8b6077c2-ecab-441a-8196-fcf736643fc6 · read 2026-08-29

  • Those labels are classed as human otc drug and human prescription drug.

    US prescribing information · 8b6077c2-ecab-441a-8196-fcf736643fc6 · read 2026-08-29

  • 23918 marketed supplement labels list this ingredient, classed as non-nutrient/non-botanical.

    NIH Dietary Supplement Label Database · 26767 · read 2026-08-29

  • Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.

    NIH Dietary Supplement Label Database · 26767 · read 2026-08-29

Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.

What it would be like to takeRead from sources, not yet reviewed

What you could measure

Watching one thing carefully can tell you whether it moved. It cannot tell you what moved it.

This is sold without a prescription, so a person can sensibly watch one thing and see whether it moves.

  1. Pick one goal. One goal only. Two at once cannot be told apart afterwards.

  2. Pick one thing to watch. Registered studies measured things like: aim 1 change in flow mediated dilation; insulin resistance; insulin sensitivity.

  3. Measure before you start. Take the same measurement several times first. One reading is not a starting point.

  4. Know the swing. Write down how much it moves on its own across a normal week.

  5. Change one thing. Change nothing else at the same time, including training and sleep.

  6. Give it the study length. No finished study window is recorded, so no length is suggested here.

  7. Track whether you took it. Missed days are the most common reason a home test shows nothing.

  8. Read the trend. Look at the line across weeks. A single reading tells you almost nothing.

What not to measure

  • Anything that swings more day to day than the change you are looking for.
  • A wearable estimate of sleep stages, which is an estimate and not a measurement.
  • Weight on one morning, which mostly records water.
  • A feeling you did not write down before starting, such as: fatigue severity scale.

When to stop

  • Stop if something new and unpleasant starts, and ask a pharmacist or doctor.
  • Stop if you cannot keep everything else steady, because the result will not mean anything.
  • Stop at the end of the window you set, and read the trend then.

Tracking can show whether something changed for you. It cannot show what caused it.

RNAWiki does not work out an amount for anyone.

What is missing or unclearRead from sources, not yet reviewed

Claims that go past the evidence

Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.

Goes past the evidence

That supplemental lipoic acid supports the mitochondrial enzymes whose cofactor it is named for, which it does not join

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That short-term symptom relief implies slowing of the underlying nerve damage

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That a 1.27 kg pooled weight difference with no dose-response is a pharmacological weight-loss effect

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That a compound well tolerated over five weeks is well tolerated over years

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

What is missing or unclearRead from sources, not yet reviewed

What nobody knows yet

Open questions, each with why it is open and what would close it.

Missing populations

Which groups were under-represented in the studies has not been recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing long-term data

No completed tested study window is recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

No reviewed conclusion

RNAWiki has not yet published a reviewed conclusion for this use.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing interaction studies

No interaction was found in the registers checked. Not finding one is not the same as showing there is none.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Formulation uncertainty

Several salts, forms or products of Alpha-lipoic acid are recorded. Results from one form may not transfer to another.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Mechanism not reviewed

No reviewed mechanism story exists for this substance.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

What happened in peopleRead from sources, not yet reviewed

Check any of this yourself

Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.

Every line above can be traced to the study named beside it. Follow the link and read it.

SYDNEY 2: symptoms improved 51% against 32% on placebo, over five weeks
In plain words
In 181 people with diabetic nerve pain, five weeks of oral lipoic acid roughly halved symptom scores, against about a third on placebo. All three doses worked equally.
What was measured
Change from baseline in Total Symptom Score, and proportion achieving a 50% or greater reduction
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
SYDNEY 2 randomised 181 diabetic patients in Russia and Israel to once-daily oral alpha-lipoic acid at 600 mg (n = 45), 1,200 mg (n = 47) or 1,800 mg (n = 46), or placebo (n = 43), for five weeks after a one-week placebo run-in. The primary outcome was change in the Total Symptom Score covering stabbing pain, burning pain, paraesthesia and numbness of the feet. Mean Total Symptom Score fell by 4.9 points (51%) on 600 mg, 4.5 (48%) on 1,200 mg and 4.7 (52%) on 1,800 mg, against 2.9 points (32%) on placebo, all P < 0.05 versus placebo. Response rates, defined as a 50% or greater reduction, were 62%, 50%, 56% and 26% respectively. Significant improvements also appeared for stabbing and burning pain, the Neuropathy Symptoms and Change score and patients' global assessment. The Neuropathy Impairment Score — the objective measure — was only numerically reduced. Note the dose-response: three doses spanning a threefold range produced essentially identical effects, which is not the shape of a dose-dependent pharmacological action and is compatible with a ceiling reached at the lowest dose or with a substantial non-specific component.
Source
Ziegler D et al. Diabetes Care 2006;29:2365-2370
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
NATHAN 1: four years, 460 patients, primary endpoint missed at P = 0.105
In plain words
The long trial designed to show that lipoic acid slows nerve damage rather than just easing symptoms did not meet its main endpoint over four years.
What was measured
Composite of Neuropathy Impairment Score lower limbs plus seven neurophysiologic tests over four years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
NATHAN 1 was a multicentre randomised double-blind parallel-group trial in 460 diabetic patients with mild-to-moderate distal symmetric sensorimotor polyneuropathy, assigned to 600 mg of oral alpha-lipoic acid once daily (n = 233) or placebo (n = 227) for four years. The primary endpoint was a composite of the Neuropathy Impairment Score in the lower limbs plus seven neurophysiologic tests. Change in that primary endpoint from baseline to four years showed no significant difference between groups (P = 0.105). Several secondary measures favoured lipoic acid: the Neuropathy Impairment Score (P = 0.028), NIS-lower limbs (P = 0.05) and the NIS-LL muscular weakness subscore (P = 0.045), with more patients showing clinically meaningful improvement and fewer showing progression on NIS (P = 0.013) and NIS-LL (P = 0.025). Nerve conduction and quantitative sensory test results did not significantly worsen on placebo, which the authors flag — a trial designed to detect slowed deterioration cannot succeed if the control group does not deteriorate. The finding that matters most for a consumer is elsewhere in the paper: serious adverse events were higher on alpha-lipoic acid at 38.1% than on placebo at 28.0%.
Source
Ziegler D et al. Diabetes Care 2011;34:2054-2060
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Lipoic acid supplementation traced to a specific form of kidney disease
In plain words
Unexpected heavy protein loss in the urine appeared in the treatment arm of a lipoic acid trial. Biopsies identified a distinct kidney lesion, and it went away when the supplement was stopped.
What was measured
Biopsy-proven NELL1-associated membranous nephropathy and proteinuria after lipoic acid supplementation, with remission on discontinuation
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Investigators running a clinical trial of lipoic acid supplementation in multiple sclerosis observed high-grade proteinuria as an unexpected adverse event specific to the treatment arm. That observation led them to identify similar patients in their nephrology practice, and they reported four biopsy-proven cases and a fifth suspected case of neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy following lipoic acid supplementation. Discontinuation of lipoic acid together with supportive therapy resulted in remission. NELL1-associated membranous nephropathy is a recently characterised subtype, and identifying an exposure that appears to cause a reversible form of it is a substantive finding. Five cases is a case series and supports no incidence estimate whatever. What it does establish is that a widely sold over-the-counter antioxidant, under investigation in multiple sclerosis, diabetes and schizophrenia, produced a biopsy-confirmed glomerular lesion in the treatment arm of a controlled study — and that nobody had been looking for it.
Source
Spain R et al. Lipoic acid supplementation associated with NELL1-associated membranous nephropathy. Kidney Int 2021;100:1208-1213
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
The supplement is not the cofactor it is named after
In plain words
Lipoic acid is famous as an essential piece of the enzymes that burn fuel in mitochondria. The lipoic acid in a capsule does not become part of those enzymes.
What was measured
That supplemental alpha-lipoic acid supports the mitochondrial dehydrogenase complexes for which lipoic acid is the named cofactor
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Endogenous lipoic acid is synthesised inside the mitochondrion by lipoyl synthase, acting on an octanoyl group already attached to the target protein, and it exists in biology almost exclusively as lipoyl-lysine covalently bound to the E2 subunits of pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, branched-chain ketoacid dehydrogenase and the glycine cleavage system. Free lipoic acid is not a normal metabolite at meaningful concentrations, and mammalian cells do not efficiently attach exogenous free lipoate to those complexes. Supplemental alpha-lipoic acid therefore acts as something else: a free, redox-active dithiol that is reduced to dihydrolipoic acid, regenerates other cellular reductants, chelates transition metals, and is rapidly beta-oxidised and cleared with a plasma half-life measured in tens of minutes. That is a legitimate pharmacology, and it is a different one from the cofactor role that supplies the molecule's reputation. Dietary lipoic acid, which occurs as protein-bound lipoyllysine, is delivered in amounts orders of magnitude below the 600 to 1,800 mg used in the trials.
Source
Ziegler D et al. Diabetes Care 2011;34:2054-2060
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
The weight loss effect is 1.27 kilograms
In plain words
Pooling ten randomised double-blind trials, lipoic acid produced about 1.3 kilograms more weight loss than placebo, and the dose made no difference.
What was measured
Mean difference in body weight and body mass index between lipoic acid and placebo groups
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Kucukgoncu and colleagues meta-analysed ten randomised, double-blind, placebo-controlled studies and found lipoic acid treatment associated with 1.27 kg greater mean weight loss than placebo (95% CI 0.25 to 2.29) and a mean BMI difference of -0.43 kg/m2 (95% CI -0.82 to -0.03). Meta-regression showed no significance of lipoic acid dose on either BMI or weight change, while study duration significantly affected BMI change but not weight change. The authors describe the effect as small and short-term and call for research on different doses and long-term benefit. Two features undercut a pharmacological reading. A weight loss effect with no dose-response across the studied range is difficult to attribute to the compound, and 1.27 kg with a confidence interval reaching 0.25 kg is within the range that dietary co-intervention and adherence effects readily produce in supplement trials.
Source
Kucukgoncu S, Zhou E, Lucas KB, Tek C. Obes Rev 2017;18:594-601
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
The programme moved from symptoms to disease modification, and the answer changed
In plain words
Short trials showed lipoic acid eases how diabetic nerve damage feels. The long trial designed to show it slows the damage itself did not succeed.
What was measured
That short-term symptom relief in diabetic neuropathy implies slowed progression of the underlying nerve damage
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The sequence is unusually clean. Five-week SYDNEY 2 measured a patient-reported symptom score and found roughly half of symptoms relieved against a third on placebo, with response rates of 50 to 62% against 26%. Four-year NATHAN 1 measured a composite of objective impairment and neurophysiology and did not meet it (P = 0.105), while several impairment secondaries did move. Read together, the honest summary is that alpha-lipoic acid is better supported as a symptomatic agent over weeks than as a disease-modifying one over years, and that its symptomatic evidence rests on subjective endpoints with no dose-response across a threefold dose range. The safety arithmetic changed too: a compound that was well tolerated over five weeks recorded serious adverse events in 38.1% of treated patients against 28.0% on placebo over four years.
Source
Ziegler D et al. Diabetes Care 2006;29:2365-2370; Ziegler D et al. Diabetes Care 2011;34:2054-2060
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim

Where else this substance is registered

CAS registry number
1077-28-7
PubChem compound
864
RxNorm concept
6417

Checks this page had to pass

  • Passed

    Identity resolved

    no open identity hold

  • Passed

    No unresolved merge across substance families

    no quarantine open

  • Passed

    Every public sentence names a source

    The opening statement carries the origin: Written into the record, not signed off.

  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

  • Passed

    No internal keys in reader text

    enforced by the copy-contract test over the rendered page

  • Passed

    Safety mode resolved

    The identity record classes it as a supplement ingredient; no medicines register records an approval.

  • Passed

    Canonical metadata present

    slug and display name present

What is missing or unclearRead from sources, not yet reviewed

How this medicine reached us

Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.

What the approval register records

  • The earliest marketing start date recorded for a listed product is 19840815.

    FDA National Drug Code directory · 0642-0207 · read 2026-08-29

What is missing or unclearRead from sources, not yet reviewed

What to learn next

Ordered by what would most change how you read this page, starting with what is easiest to misunderstand.

This order is fixed in code and does not count clicks or time on the page.

What is not here

3 questions this page could not answer

These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.

  • What it may clash with — found nothing in the sources checked.
  • Other ways to the same goal — found nothing in the sources checked.
  • What changed on this page — found nothing in the sources checked.

The record as stored

The full record, for auditing

Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.

The older medicine-wide conclusion held in this record

Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.

Five weeks of oral alpha-lipoic acid reduced diabetic neuropathy symptom scores by about half against a third on placebo, but the four-year NATHAN 1 trial missed its primary composite endpoint at P = 0.105 with serious adverse events in 38.1% on treatment against 28.0% on placebo, and in 2021 five cases of NELL1-associated membranous nephropathy were traced to lipoic acid supplementation.

Recorded evidence blocks (15)

What did Alpha-lipoic acid's largest trial (1526 people) and its longest (13 years) measure?


1526 people in Alpha-lipoic acid's largest registered study, 13 years in its longest registered window, measuring mortality. ClinicalTrials.gov · 2026-09-01

29 phase2, 28 na, 19 phase3, 14 phase4, 11 phase1, 2 early phase1; NCT02115724; 2027-01. Last human test completed 2026, NCT06040190.

Interpretation These counts include studies where Alpha-lipoic acid was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.

Show the evidence
  • phase2
    29
  • na
    28
  • phase3
    19
  • phase4
    14
  • phase1
    11
  • early phase1
    2
1 more recorded row
  • Last recorded human test NCT06040190
    2026-07-01

recorded 2026-09-01 · last checked 2026-09-04

From C. elegans to human: where has Alpha-lipoic acid shown lifespan?


C. elegans: lifespan, Drosophila: mechanism-only, mouse: lifespan, rat: mechanism-only and human: lifespan (90): the rungs where Alpha-lipoic acid has a recorded finding. Europe PMC and ClinicalTrials.gov · organism ladder · 2026-09-01

Interpretation mortality — the recorded outcome words.

Yeast C. elegans lifespanDrosophila mechanism-onlyMouse lifespanRat mechanism-onlyDog Non-human primate Human lifespan
Show the evidence
  • C. elegans
    lifespan
  • Drosophila
    mechanism-only
  • mouse
    lifespan
  • rat
    mechanism-only
  • human NCT01888861
    lifespan; mortality; 90

recorded 2026-09-01 · last checked 2026-09-04

4 of Alpha-lipoic acid's trials stopped: accrual/recruitment, other?


accrual/recruitment (2) and other (2): Alpha-lipoic acid's stop wording, clustered. ClinicalTrials.gov · 2026-09-01

"because of withdrawal of Avandia sale due to its risks outweigh its benefits"; 4 of 90 registered studies

Show the evidence

Trial

  • NCT01406704
    terminated; "because of withdrawal of Avandia sale due to its risks outweigh its benefits"
  • NCT01880372
    terminated; "Low number of patients enrolled"
  • NCT04021550
    withdrawn; "Covid-19 Pandemic prevented this study from beginning"
  • NCT05945160
    withdrawn; "Funding was terminated, the study will not enroll any subjects"

recorded 2026-09-01 · last checked 2026-09-04

Human studies of Alpha-lipoic acid used Alpha-Lipoic Acid 600mg — over how long?


Human studies of Alpha-lipoic acid used "Alpha-Lipoic Acid 600mg". ClinicalTrials.gov · 2026-09-01

11 recorded entries; human; tablet, oral; also "Alpha lipoic acid 300mg", "Pregabalin 150mg + Alpha-lipoic acid 480mg", "Alpha-Lipoic Acid 480mg"

Show the evidence

human

  • NCT04021550
    Alpha-Lipoic Acid 600mg
  • NCT04064814
    Alpha lipoic acid 300mg
  • NCT04846673
    Pregabalin 150mg + Alpha-lipoic acid 480mg
  • NCT04846673
    Alpha-Lipoic Acid 480mg
  • NCT05009901
    Alpha Lipoic Acid 600 MG Oral Tablet
  • NCT05023863
    Alpha Lipoic Acid 600 MG Oral Tablets
5 more recorded rows
  • human NCT05679037
    Alpha Lipoic Acid 600 MG Oral Capsule
  • human NCT05945160
    Alpha Lipoic Acid 300mg
  • human NCT06253429
    tablet; Alpha lipoic acid 300 mg tablet
  • human NCT07182526
    oral; Alpha lipoic acid 600 mg oral Tablet, Nutricost pharmacetics
  • human NCT07574684
    Alpha Lipoic Acid 600mg

recorded 2026-09-01 · last checked 2026-09-04

More Alpha-lipoic acid was worse in human: at what point?


Hormetic in human: "The endogenous and dietary agent, alpha lipoic acid (ALA), is evaluated for its capacity to induce a broad spectrum of adaptive responses via hormetic dose responses and their underlying mechanisms." Europe PMC · dose-response search · 2023-05-10

4 recorded sentences naming Alpha-lipoic acid; hormetic, dose-response, biphasic

Show the evidence
  • hormetic PMID 37169059
    "The endogenous and dietary agent, alpha lipoic acid (ALA), is evaluated for its capacity to induce a broad spectrum of adaptive responses via hormetic dose responses and their underlying mechanisms."
  • dose-response PMID 32091656
    "There are numerous trials reported the effect of alpha-lipoic acid (ALA) on obesity measurements; while no summarised dose-response meta-analysis is available to address the effects of dose and duration of ALA supplementation on obesity measurements."
  • biphasic PMID 10512372
    "Alpha-lipoic acid had a biphasic effect: it dose-dependently increased fructose, glucose, and sorbitol, peaking at 25 mg/kg, and then fell beyond that dose, and it dose-dependently increased myo-inositol."
  • dose-response PMID 8922368
    "Thioctic acid provoked an upward shift of the glucose-uptake insulin dose-response curve."

recorded 2023-05-10 · last checked 2026-09-04

Alpha-lipoic acid's half-life is 0.5 hours — which schedules were studied?


0.5 hours, the half-life Alpha-lipoic acid's label states. openfda-label · 2026-08-28

bioavailability about 30% %.

Show the evidence
  • half life
    0.5 hours hours; The decline observed in the plasma concentration was steep (t1/2, 0.5 h).
  • bioavailability
    about 30% %; Exogenous racemic alpha-lipoic acid orally administered for the symptomatic treatment of diabetic polyneuropathy is readily and nearly completely absorbed, with a limited absolute bioavailability of about 30% caused by high hepatic extraction.

recorded 2026-08-28 · last checked 2026-09-04

Could one person measure Alpha-lipoic acid's effect on aim 1 change in flow mediated dilation?


Aim 1 change in flow mediated dilation: measured in Alpha-lipoic acid's trials.

aim 1 change in flow mediated dilation is the recorded endpoint.

Show the evidence

biomarkers

  • aim 1 change in flow mediated dilation; 2026-09-01
  • f2 isoprostane; 2026-09-01
  • ototoxicity measurement; 2026-09-01
  • forearm blood flow; 2026-09-01
  • insulin resistance; 2026-09-01
  • biomarkers of oxidative stress; 2026-09-01
14 more recorded rows
  • biomarkers
    insulin sensitivity; 2026-09-01
  • biomarkers
    endothelial function; 2026-09-01
  • biomarkers
    activities of daily living at 18 months; 2026-09-01
  • biomarkers
    brain atrophy by mri; 2026-09-01
  • biomarkers
    spirometric fvc values at baseline; 2026-09-01
  • biomarkers
    spirometric fvc values at endpoint; 2026-09-01
  • biomarkers
    spirometric fev1 values at baseline; 2026-09-01
  • biomarkers
    spirometric fev1 values at endpoint; 2026-09-01
  • biomarkers
    spirometric fef values at baseline; 2026-09-01
  • biomarkers
    spirometric fef values at endpoint; 2026-09-01
  • biomarkers
    body weight; 2026-09-01
  • biomarkers
    fatigue severity scale; 2026-09-01
  • biomarkers
    histological evaluation; 2026-09-01
  • biomarkers
    appetite suppression; 2026-09-01
  • half life
    2026-09-04; halfLife; hours; 0.5 hours; 2026-08-28
  • human trials at or under30
    19
  • smallest human trial
    0; NCT04021550; EARLY_PHASE1; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; WITHDRAWN

Which of 24 hour blood pressure, activities of daily living at 18 months and acute change in exercise capacity did Alpha-lipoic acid's trials measure?


24 hour blood pressure, activities of daily living at 18 months and acute change in exercise capacity lead 40 outcome terms across Alpha-lipoic acid's trials. ClinicalTrials.gov · 2026-09-01

forearm blood flow, insulin resistance, biomarkers of oxidative stress, insulin sensitivity, endothelial function and activities of daily living at 18 months follow.

Show the evidence
  • aim 1 change in flow mediated dilation
    1
  • f2 isoprostane
    1
  • ototoxicity measurement
    1
  • forearm blood flow
    1
  • insulin resistance
    1
  • biomarkers of oxidative stress
    1
14 more recorded rows
  • insulin sensitivity
    1
  • endothelial function
    1
  • activities of daily living at 18 months
    1
  • brain atrophy by mri
    1
  • spirometric fvc values at baseline
    1
  • spirometric fvc values at endpoint
    1
  • spirometric fev1 values at baseline
    1
  • spirometric fev1 values at endpoint
    1
  • spirometric fef values at baseline
    1
  • spirometric fef values at endpoint
    1
  • body weight
    1
  • fatigue severity scale
    1
  • histological evaluation
    1
  • appetite suppression
    1

recorded 2026-09-01 · last checked 2026-09-04

Which of Alpha-lipoic acid's 16 ongoing trials reports first?


16 registered trials of Alpha-lipoic acid are open; earliest completion 2025-12-28. ClinicalTrials.gov · 2026-09-01

Acute Change in Flow mediated dilation; Changes in the Insulin sensitivity index (SI) obtained from FSIGT, in (mU/L)^-1 * min^-1; latest 2030-12-01

Show the evidence

Trial

  • NCT02115724
    "Nitric Oxide Bioavailability and Early Life Stress (NO-Stress)"; n 74; "Acute Change in Flow mediated dilation"; 2027-01
  • NCT02690064
    "Mechanisms for Vascular Dysfunction and Exercise Tolerance in CF"; n 13; "Acute Change in Flow mediated dilation"; 2027-01
  • NCT05713799
    "Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity"; n 60; "Changes in the Insulin sensitivity index (SI) obtained from FSIGT, in (mU/L)^-1 * min^-1"; 2030-03-01
  • NCT06286098
    "Alpha Lipoic Acid in Pediatrics on Hemodialysis"; n 50; "Serum level of E-Selectin"; 2028-03-01
  • NCT07157722
    "Evaluating the Effect of N-Acetyl Cysteine and Alpha Lipoic Acid in Patients With Beta Thalassemia"; n 66; "The change from baseline in carotid intima media thickness (CIMT)"; 2026-01-30
  • NCT07182526
    "Effects of Adding Quercetin or Alpha Lipoic Acid to Usual Care on Symptoms and Blood Markers in Iraqi Women With Polycystic Ovary Syndrome"; n 150; "Change in Hormonal Profile (LH, FSH, Testosterone) from Baseline"; 2026-05-01
10 further recorded trials
  • NCT07256119
    "Evaluation of the Effect of Alpha Lipoic Acid on Radiation Induced Dermatitis in Breast Cancer Patients"; n 40; "Incidence of development of radiation induced dermatitis (RID)"; 2025-12-28
  • NCT07360379
    "Comparing N-Acetylcysteine (NAC) Versus Alpha-Lipoic Acid (ALA) as Adjuncts for Postoperative Pain Management After Laparoscopic Appendectomy"; n 180; "Visual analogue scale (VAS)"; 2026-05
  • NCT07381361
    "Photobiomodulation Therapy vs. Alpha-Lipoic Acid in Burning Mouth Syndrome Treatment"; n 60; "Visual Analogue Scale (VAS)"; 2026-03-10
  • NCT07456176
    "Effect of Low-Dose Versus High-Dose Alpha-Lipoic Acid on Oxidative Stress, Inflammation, and Clinical Outcomes in Acute Exacerbations of Chronic Obstructive Pulmonary Disease"; n 75; "Oxidative Stress & Inflammatory Biomarkers"; 2026-06-01
  • NCT07564479
    "Alpha-Lipoic Acid in Mitigating Cisplatin-Induced Nephrotoxicity"; n 50; "Change in SCr and CrCl in patients receiving Cisplatin Chemotherapy + Alpha-Lipoic Acid compared to Control Group"; 2027-06
  • NCT07574684
    "Clinical Effects of Alpha-Lipoic Acid in Advanced NSCLC"; n 60; "1. Clinical Benefit Rate (CBR)"; 2027-04-20
  • NCT07630779
    "Efficacy of Alpha Lipoic Acid Combined With Myo-Inositol in Non-Diabetic PCOS Patients"; n 180; "Ovulation Rate"; 2026-12
  • NCT07685431
    "Alpha-Lipoic Acid Supplementation and IVF Outcomes in Women of Advanced Maternal Age"; n 60; "Embryo quality"; 2028-06-30
  • NCT07725484
    "Efficacy of Lipoic Acid on Chronic Ischemic Heart Failure Patients"; n 1526; "Major Adverse Cardiovascular Events (MACE)"; 2030-12-01
  • NCT07785544
    "Efficacy and Safety of Low-Dose Duloxetine Plus Alpha-Lipoic Acid Versus Standard-Dose Duloxetine in Painful Diabetic Peripheral Neuropathy"; n 170; "Change in pain intensity measured by Numerical Rating Scale (NRS) from baseline to Week 9"; 2027-08

recorded 2026-09-01 · last checked 2026-09-04

Which running trial of Alpha-lipoic acid could settle insulin sensitivity?


NCT05713799 measures Changes in the Insulin sensitivity index (SI) obtained from FSIGT, in (mU/L)^-1 * min^-1, reading out 2030-03-01.

1 open trial; n 60; "Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity"

Show the evidence
  • Trial NCT05713799
    "Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity"; n 60; "Changes in the Insulin sensitivity index (SI) obtained from FSIGT, in (mU/L)^-1 * min^-1"; 2030-03-01

Which 35 trials of Alpha-lipoic acid posted no result?


Posted no result
35 of 35 completed trials
Registrations
NCT00033176, NCT00010842, NCT00079807, NCT00308971, NCT00490867 and NCT00795262, and 29 more
Completion dates
oldest 2004-08; newest 2024-05-05
Show the evidence

Trial

  • NCT00033176
    2004-08
  • NCT00010842
    2004-12
  • NCT00079807
    2007-02
  • NCT00308971
    2007-07
  • NCT00490867
    2007-08
  • NCT00795262
    2009-07
14 further recorded trials
  • NCT00994513
    2010-05
  • NCT01515839
    2010-06
  • NCT00505427
    2010-07
  • NCT00845156
    2010-09
  • NCT01056497
    2011-06
  • NCT01355952
    2012-12
  • NCT01696448
    2013-04
  • NCT00112996
    2014-04
  • NCT01877590
    2015-07
  • NCT01524861
    2016-01
  • NCT01381354
    2016-05
  • NCT02382328
    2016-07
  • NCT02775266
    2016-10
  • NCT02937363
    2017-07

At the median, Alpha-lipoic acid's trials enrolled 60 people — anything larger?


Median enrolment
60
Largest enrolment
1526
Registered trials counted
89

What do 55 spontaneous reports say about Alpha-lipoic acid — and not say?


These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.

Alpha-lipoic acid appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 55 reaction mentions were counted: drug-induced liver injury 8; hepatotoxicity 8; hepatic cirrhosis 7; hepatic encephalopathy 7. open-targets-adr · CHEMBL33864 · 2026-06-24

Show the evidence
  • drug-induced liver injury
    8
  • hepatotoxicity
    8
  • hepatic cirrhosis
    7
  • hepatic encephalopathy
    7
  • hepatic necrosis
    7
  • drug interaction
    6
4 more recorded rows
  • areflexia
    3
  • diabetic neuropathy
    3
  • glycosylated haemoglobin increased
    3
  • muscle contractions involuntary
    3

recorded 2026-06-24 · last checked 2026-09-04

Was Alpha-lipoic acid studied with exercise?


exercise is named in Alpha-lipoic acid's label sentences: "The study included 82 participants allocated into the intervention group (alpha-lipoic acid and exercise on 15 consecutive therapeutic days, <i>n</i> = 42) and control group (alpha lipoic acid only, <i>n</i> = 40)." openfda-label+europepmc · 2024-12-01

1 recorded statement; exercise

Show the evidence
  • exercise
    The study included 82 participants allocated into the intervention group (alpha-lipoic acid and exercise on 15 consecutive therapeutic days, <i>n</i> = 42) and control group (alpha lipoic acid only, <i>n</i> = 40).

recorded 2024-12-01 · last checked 2026-09-04

What is recorded about Alpha-lipoic acid and AMPK?


"This study investigated the synergistic neuroprotective potential of alpha-lipoic acid (ALA) and metformin through the coordinated activation of Nrf2 and AMPK signaling pathways in type 2 diabetes mellitus (T2DM)-induced encephalopathy." — where Alpha-lipoic acid and AMPK appear together. Europe PMC · pathway abstract search · 2025-07-18

AMPK, autophagy, sirtuin; PMID 40723442, 39261583, 35098396, 32715610

Show the evidence

AMPK

  • PMID 40723442
    "This study investigated the synergistic neuroprotective potential of alpha-lipoic acid (ALA) and metformin through the coordinated activation of Nrf2 and AMPK signaling pathways in type 2 diabetes mellitus (T2DM)-induced encephalopathy."
  • PMID 39261583
    "Alpha lipoic acid (ALA), an indirect AMPK activator that inhibits hepatic steatosis, shows antitumor effects in different cancers."
  • "Alpha lipoic acid (ALA), an indirect AMPK activator that inhibits hepatic steatosis in rodents, shows antitumor effects in different cancers."

autophagy

  • PMID 35098396
    "The present work was designed to determine the possible synergistic effects of alpha-lipoic acid (LA) preconditioning and IPostC on myocardial I/R damage in type-II diabetic rats through modulating autophagy, and the involvement of mitochondrial function."
  • PMID 32715610
    "In this issue of EMBO Reports, Du et al report that alpha-lipoic acid (ALA) sustains an active endocytosis-autophagy network that effectively reverses age-dependent ISC hyperplasia in Drosophila (Du et al, 2020)."
  • sirtuin
    "This recycling causesactivation-induced cell death, suppresses lymphocyte countproliferation, and leads to IL-1β hypersecretion and worsening RHC.Ultimately, this cytokine storm and severe RHC induce autoimmunity.Evidence suggests this pathological state can be avoided by restoring calcium homeostasis using a combination of DHEA, vitaminD3/calcitriol, magnesium, ubiquinone, and the AMPK/SIRT1…"

recorded 2025-07-18 · last checked 2026-09-04

Where it is registered
Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL33864
PubChem CID
864
CAS number
1077-28-7
RxCUI
6417
InChIKey
AGBQKNBQESQNJD-UHFFFAOYSA-N
Also called
LIPOIC ACID, ALPHA, 6,8-thioctic acid, Acidum thiocticum, A-lipoicum acidum, Biletan, Dl-6,8-thioctic acid, Lipoic acid, dl-, Thiocacid, Thioctan, Thioctate, Thioctic acid, Thioctic acid dl-form
Development code
NSC-628502, NSC-90788
Trade name
Thioctacid, Chronagesic, High Vitality Tab, Mitochondria Pro, Bio Co-Enzyme Phase, Strovite One Caplets, Ultra Slim 30, Metal-Chord, Guna Arthro Relief, Adaptopath, Hgh Vitality, Guna-Arthro
Sources (11)

Sources

  • ClinicalTrials.gov clinicaltrials.gov ·
  • ClinicalTrials.gov ClinicalTrials.gov API v2 snapshot 2026-09-01T09:00:05 ·
  • this record's own fields 2,3,5 ·
  • Europe PMC dose-response search ·
  • Europe PMC pathway abstract search ·
  • Europe PMC search ·
5 more sources

ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work

How these records are assembled · Which registers were checked

Index-quality checks
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  • required summary fields resolved: 5 required field(s) not terminal: Why people use it, Best-supported result, Most important common problem, Biggest unanswered question, Human evidence
  • public claims reviewed: 0 reviewed claim(s); drafts are never rendered
  • source coverage passed: 11 source rows
  • no critical contamination: no quarantine open
  • canonical metadata passed: slug and display name present
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