Comparison
Lion's Mane vs MOTS-c
Side-by-side of Lion's Mane 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.
Lion's Mane
Lion's mane mushroom (Hericium erinaceus) supplement profile: hericenones and erinacines stimulate NGF in vitro. Human cognition trials are small.
MOTS-c
MOTS-c peptide is a 16-amino-acid mitochondrial-derived peptide. Preclinical signals for insulin sensitivity, exercise capacity, dosage notes.
Effects at a glance
Lion's Mane
- •Edible medicinal mushroom containing NGF-stimulating hericenones and erinacines
- •Mori 2009 trial (n=30) in mild cognitive impairment showed cognitive improvement at 3 g/day for 16 weeks, reversing 4 weeks after discontinuation
- •Saitsu 2019 (n=31) in older adults reported MoCA improvements at 3.2 g/day over 12 weeks
- •Multiple small mood trials suggest reduced anxiety and depression scores at 1 to 4 g/day extract
- •Mechanistic case rests on NGF stimulation and remyelination support; in vivo human NGF measurement is absent
- •Product quality varies substantially; mycelium-on-grain products can be over 50% grain by weight
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 | Lion's Mane | MOTS-c |
|---|---|---|
| Category | natural | peptide |
| Also known as | Hericium erinaceus, Yamabushitake, Bearded Tooth, Hou Tou Gu | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc |
| Half-life (hr) ↗ | 6 | 0.5 |
| Typical dose (mg) ↗ | 1000 | 5 |
| Dosing frequency | 1 to 2 times daily | 2-3x weekly |
| Routes | oral | subcutaneous |
| Onset (hr) | 168 | 1 |
| Peak (hr) | 1344 | 4 |
| Molecular weight | - | 1880.18 |
| Molecular formula | mixed extract | C82H132N22O25S2 |
| Mechanism | Hericenones and erinacines stimulate NGF mRNA expression and NGF protein release in cultured neurons; secondary anti-inflammatory and remyelination-supportive activity in preclinical models. | 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 and food worldwide; unscheduled and unrestricted | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List |
| WADA status | allowed | unknown |
| DEA / Rx | OTC supplement and food | Not scheduled (research chemical) |
| Pregnancy | Insufficient data for routine supplementation; consumed historically as food without documented harm | Insufficient data; not recommended |
| CAS | 1627580-64-6 | |
| PubChem CID | 139599184 | |
| Wikidata | Q146050 | Q24832108 |
Safety profile
Lion's Mane
Common side effects
- mild GI upset
- occasional skin rash
- contact dermatitis (rare)
Contraindications
- mushroom allergy
Interactions
- anticoagulants: theoretical antiplatelet effect, no documented clinical events(minor)
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?
Lion's Mane 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 focus or working memory, pick Lion's Mane.
- → If your priority is nerve health, pick Lion's Mane.
- → If your priority is healthspan extension, pick MOTS-c.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
Edge case: If you want to avoid research-only / gray-market sourcing, Lion's Mane is the more accessible choice.
Default choice: Lion's Mane. 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 Lion's Mane and MOTS-c?
Lion's Mane and MOTS-c differ in category (natural vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Lion's Mane or MOTS-c?
Lion's Mane half-life is 6 hours; MOTS-c half-life is 0.5 hours.
Can you stack Lion's Mane 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.
Go deeper