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BiologicalX

Comparison

Alpha-Lipoic Acid vs MOTS-c

Side-by-side of Alpha-Lipoic Acid and MOTS-c. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.

Effects at a glance

Alpha-Lipoic Acid

  • Approved Rx for diabetic neuropathy in Germany at 600 mg/day IV (Thioctacid) since 1960s
  • Improves neuropathy symptoms (TSS, NIS) at 600 mg/day IV across ALADIN and SYDNEY trials
  • R-ALA enantiomer absorbs 40-100% better than racemic mixtures
  • Activates AMPK; produces small HbA1c reductions in T2DM
  • Plasma half-life ~30 minutes; split dosing or sustained-release is standard
  • Hypoglycemia risk with insulin or sulfonylureas; medication adjustment may be required

MOTS-c

  • 16-amino-acid peptide encoded in mitochondrial DNA (12S rRNA region); discovered 2015
  • Activates AMPK in skeletal muscle and liver; improves insulin sensitivity in rodent models
  • Circulating endogenous levels decline with age, motivating the longevity-restoration hypothesis
  • CohBar's MOTS-c analog CB4211 discontinued after phase 1b NASH readout did not meet endpoints
  • Anecdotal protocols use 5 to 10 mg subcutaneously 2 to 3 times weekly
  • Not on the WADA Prohibited List as of 2026; future scrutiny likely given exercise-mimetic mechanism

Side-by-side

Attribute Alpha-Lipoic Acid MOTS-c
Category supplement peptide
Also known as ALA, thioctic acid, R-ALA, R-lipoic acid Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc
Half-life (hr) 0.5 0.5
Typical dose (mg) 600 5
Dosing frequency 1 to 3 times daily on empty stomach 2-3x weekly
Routes oral, iv subcutaneous
Onset (hr) 0.5 1
Peak (hr) 1 4
Molecular weight 206.33 1880.18
Molecular formula C8H14O2S2 C82H132N22O25S2
Mechanism Dual lipid- and water-soluble antioxidant; redox cycles with dihydrolipoic acid (DHLA) to scavenge ROS, regenerate vitamin E and C, and chelate transition metals. Activates AMPK in liver and muscle; cofactor for pyruvate and alpha-ketoglutarate dehydrogenase complexes. Mitochondrial-derived peptide that activates AMPK in skeletal muscle and liver, improves insulin sensitivity, and translocates to the nucleus under metabolic stress to modulate nuclear gene expression in retrograde mitochondrial signaling.
Legal status Dietary supplement (US, UK, Canada, most EU); prescription drug for diabetic neuropathy in Germany Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List
WADA status allowed unknown
DEA / Rx Not scheduled Not scheduled (research chemical)
Pregnancy Insufficient data; precautionary avoidance Insufficient data; not recommended
CAS 62-46-4 1627580-64-6
PubChem CID 864 139599184
Wikidata Q161227 Q24832108

Safety profile

Alpha-Lipoic Acid

Common side effects

  • nausea
  • abdominal discomfort
  • diarrhea
  • sulfurous odor
  • rash (rare)

Contraindications

  • pregnancy and lactation (insufficient safety data)
  • active insulin autoimmune syndrome predisposition

Interactions

  • insulin and sulfonylureas: additive hypoglycemia; medication dose adjustment may be required(major)
  • thyroid hormone: may reduce T4 to T3 conversion at high doses(moderate)
  • biotin: ALA competes with biotin uptake; chronic use can induce biotin insufficiency(minor)
  • iron supplements: ALA chelates iron and reduces absorption; separate dosing(moderate)
  • chemotherapy (oxidative-stress-dependent agents): theoretical interference; coordinate with oncology team(moderate)

MOTS-c

Common side effects

  • injection-site irritation
  • transient fatigue
  • headache (anecdotal)

Contraindications

  • pregnancy
  • lactation
  • active malignancy (theoretical)
  • severe hypoglycemia risk on concurrent insulin or sulfonylurea

Interactions

  • insulin: additive insulin sensitization may increase hypoglycemia risk(moderate)
  • metformin: both activate AMPK; theoretical additive metabolic effect, no controlled data(minor)
  • sulfonylureas: increased hypoglycemia risk via additive insulin sensitization(moderate)

Which Should You Take?

Alpha-Lipoic Acid comes out ahead for most readers on the criteria we weight: 3 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-B outcome catalogued. MOTS-c is the right call when one of the conditionals below applies.

  • If your priority is long-term neuroprotection, pick Alpha-Lipoic Acid.
  • If your priority is mitochondrial function, pick MOTS-c.
  • If your priority is metabolic health and glucose control, pick Alpha-Lipoic Acid.

Edge case: If you want to avoid research-only / gray-market sourcing, Alpha-Lipoic Acid is the more accessible choice.

Default choice: Alpha-Lipoic Acid. Lower friction to source, and broader goal coverage. Reach for MOTS-c only if your priority sits squarely in the goals it owns above.

This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.

Common questions

What is the difference between Alpha-Lipoic Acid and MOTS-c?

Alpha-Lipoic Acid and MOTS-c differ in category (supplement vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.

Which has a longer half-life, Alpha-Lipoic Acid or MOTS-c?

Alpha-Lipoic Acid half-life is 0.5 hours; MOTS-c half-life is 0.5 hours.

Can you stack Alpha-Lipoic Acid with MOTS-c?

Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.

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