Comparison
L-Theanine vs MOTS-c
Side-by-side of L-Theanine 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.
L-Theanine
L-theanine is a non-protein amino acid found in tea leaves. The most-replicated nootropic; pairs with caffeine at 1:1 (100-200 mg each) for acute focus.
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
L-Theanine
- •Non-protein amino acid in tea; the most-replicated nootropic in the human RCT literature
- •Caffeine + theanine at 1:1 (100-200 mg each) is the gold-standard acute focus stack
- •Solo doses of 200-400 mg reduce subjective stress and improve sleep quality
- •Increases alpha-wave EEG activity within 30-45 minutes of 200 mg oral dose
- •Crosses blood-brain barrier; bioavailability high, half-life 60-90 minutes
- •Clean safety record; minimal interactions at supplement doses
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 | L-Theanine | MOTS-c |
|---|---|---|
| Category | supplement | peptide |
| Also known as | theanine, gamma-glutamylethylamide | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc |
| Half-life (hr) ↗ | 1.5 | 0.5 |
| Typical dose (mg) ↗ | 200 | 5 |
| Dosing frequency | as needed (with caffeine) or daily | 2-3x weekly |
| Routes | oral | subcutaneous |
| Onset (hr) | 0.5 | 1 |
| Peak (hr) | 1 | 4 |
| Molecular weight | 174.2 | 1880.18 |
| Molecular formula | C7H14N2O3 | C82H132N22O25S2 |
| Mechanism | Crosses BBB; modulates GABA/dopamine/serotonin (modest); increases alpha-wave EEG activity; dampens stress-induced sympathetic response without sedation. | 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 | OTC dietary supplement | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List |
| WADA status | allowed | unknown |
| DEA / Rx | OTC supplement | Not scheduled (research chemical) |
| Pregnancy | Insufficient supplement-dose data; tea-source intake safe | Insufficient data; not recommended |
| CAS | 3081-61-6 | 1627580-64-6 |
| PubChem CID | 439378 | 139599184 |
| Wikidata | Q909931 | Q24832108 |
Safety profile
L-Theanine
Common side effects
- mild GI upset (rare)
- headache (rare)
Contraindications
- pregnancy / lactation (insufficient data at supplement doses)
- concurrent strong GABAergics without caution
Interactions
- caffeine: synergistic for acute focus; dampens jitter without blunting alertness(minor)
- benzodiazepines / alcohol: potential additive sedation(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?
L-Theanine comes out ahead for most readers on the criteria we weight: 3 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-A outcome catalogued. MOTS-c is the right call when one of the conditionals below applies.
- → If your priority is focus or working memory, pick L-Theanine.
- → If your priority is stress and HPA-axis regulation, pick L-Theanine.
- → 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, L-Theanine is the more accessible choice.
Default choice: L-Theanine. Lower friction to source, a Tier-A evidence outcome catalogued, 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 L-Theanine and MOTS-c?
L-Theanine 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, L-Theanine or MOTS-c?
L-Theanine half-life is 1.5 hours; MOTS-c half-life is 0.5 hours.
Can you stack L-Theanine 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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