Side-by-side · Research reference
5-Amino-1MQvsMOTS-c
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongDraft8/38 cited
BAnimal-StrongReviewed16/68 cited
5-Amino-1MQ
NNMT inhibitor · Methylation / SAM modulation
Oral · Once daily fasted
MOTS-c
Mitokine · Mitochondria-Encoded
SQ · Variable · 2–3×/week
01Mechanism of Action
Parameter
5-Amino-1MQ
MOTS-c
Primary target
Nicotinamide N-methyltransferase (NNMT)Neelakantan 2018
Mitochondrial 12S rRNA sORF → folate-AICAR-AMPK axisLee 2015
Pathway
NNMT inhibition → preserved cellular SAM + NAD⁺ → restored methylation balance + ↑ thermogenic gene expressionNeelakantan 2018
Downstream effect
Reversal of HFD-induced obesity in murine models; improved metabolic profileNeelakantan 2018
Enhanced fatty acid oxidation, GLUT4-mediated glucose uptake, mitochondrial bioenergetics, anti-inflammationLee 2015
Origin
Selective small-molecule inhibitor designed in academic medicinal chemistry programsNeelakantan 2018
Endogenous 16-AA mitokine; mtDNA-encoded; declines with age; upregulated by exerciseReynolds 2021
Antibody development
—
—
02Dosage Protocols
Parameter
5-Amino-1MQ
MOTS-c
Standard dose
100–200 mg / day oralNeelakantan 2018
Anecdotal community range; murine doses scaled.
5–10 mg / weekLee 2015
Experimental, extrapolated from animal data. No human RCT-derived dose.
Frequency
Once daily, fasted
2–3× per week
Short half-life may necessitate more frequent dosing for saturation.
Lower / starter dose
50 mg / day
2.5–5 mg / week
Recommended due to limited human data.
Evidence basis
Animal-strong; no human RCT dataNeelakantan 2018
Animal + anecdotalLee 2015Reynolds 2021A first-in-human phase 1 study 2021
Phase 1a/1b CB4211 analog trial completed 2021; no native MOTS-c RCT published.
Duration
8–12 weeks per cycle
4–12 weeks (experimental)
Optimal cycle length unknown.
Form
Oral capsule
—
Timing
Morning fasted preferred
Pre-workout or fasted state preferred
Activity-context amplifies AMPK response.
Half-life
Hours (estimated; no human PK published)
Minutes to hours (estimated)
Systemically unstable; native MOTS-c PK in humans not fully characterised.
Reconstitution
—
Bacteriostatic water, 1–2 mL
10 mg/mL at 1 mL.
03Metabolic / Fat Loss Evidence
Parameter
5-Amino-1MQ
MOTS-c
Primary fat target
—
Diet-induced / metabolic obesity; systemic fat utilization
Quantified reduction
—
Significant HFD fat gain ↓Lee 2015
Murine models, dose-dependent (5 & 15 mg/kg).
IGF-1 impact
—
No direct IGF-1 pathway; AMPK-mediated
Effect on lean mass
—
High dose significantly ↑ lean mass in mice
Triglycerides
—
AMPK-driven FA oxidation suggests TG benefit (not directly measured)
Effect reversibility
—
Unknown — no long-term follow-up data
Key publication
—
Lee Cell Metab 2015 · Reynolds Nat Commun 2021 · Kim Cell Metab 2018Lee 2015Reynolds 2021Kim 2018
04Side Effects & Safety
Parameter
5-Amino-1MQ
MOTS-c
GI symptoms
Mild nausea (anecdotal)
Nausea, stomach discomfort (reported)
Methylation disruption
Theoretical risk if NNMT is over-inhibited (B vitamin metabolism)
—
Long-term safety
Unknown — no human trials
—
Cancer risk
Unclear — NNMT also studied in oncology contexts
Contradictory data — some models suggest pro-proliferative effects
Pregnancy / OB
Avoid
Avoid — insufficient safety data
Drug interactions
Theoretical with niacin / B-vitamin supplements
—
Injection site reaction
—
Mild irritation (reported)
Fluid retention / Edema
—
Not reported
Cardiovascular
—
Heart palpitations (anecdotal); cardiac hypertrophy reversed in diabetic rats
CNS / Neurological
—
Insomnia, headache (anecdotal reports)
Antibody formation
—
No data (no long-term human trials)
Evidence quality
—
Phase 1 analog (CB4211); preclinical; anecdotal humanA first-in-human phase 1 study 2021
Absolute Contraindications
5-Amino-1MQ
- ·Pregnancy / breastfeeding
- ·Active malignancy
MOTS-c
- ·Pregnancy / breastfeeding (insufficient data)
Relative Contraindications
5-Amino-1MQ
- ·Methylation-sensitive conditions (MTHFR mutation)
- ·Concurrent niacin / NAD+ precursor supplementation (theoretical interference)
MOTS-c
- ·Active cancer or cancer predisposition
- ·AMPK pathway deficiency (efficacy nullified)
- ·Use with cancer-promoting medications (theoretical)
05Administration Protocol
Parameter
5-Amino-1MQ
MOTS-c
1. Form
Oral capsule. No injection.
Add 1–2 mL bacteriostatic water. At 10 mg/vial, 1 mL gives 10 mg/mL concentration. Roll gently to dissolve.
2. Administration
Take with water, fasted preferred.
Subcutaneous — abdomen, thigh, or deltoid. Rotate sites to avoid lipohypertrophy. Pinch fat layer.
3. Timing
Morning fasted.
Pre-workout or fasted state preferred — metabolic context amplifies AMPK response. 2–3× per week.
4. Storage
Room temp ≤25 °C, dry place.
Lyophilised: room temp, protected from light. Reconstituted: refrigerate, use within 21–30 days. Short systemic stability.
5. Caveat
Monitor B-vitamin status with chronic use.
27–31G insulin syringe. Short needle (4–6 mm) for SQ delivery. Clean technique mandatory.
06Stack Synergy
5-Amino-1MQ
— no documented stacks
MOTS-c
+ Ipamorelin
ModerateMOTS-c activates AMPK/PGC-1α for mitochondrial efficiency and fatty acid oxidation; ipamorelin stimulates GH for anabolic recovery and sleep depth. Pathways are complementary — MOTS-c handles metabolic flexibility and glucose handling while ipamorelin drives recovery and body recomposition through GH. Theoretical synergy is high; clinical data is lacking.
- MOTS-c
- 5 mg SQ · pre-workout (2–3×/wk)
- Ipamorelin
- 200–300 mcg SQ · pre-sleep (daily)
- Primary benefit
- Metabolic flexibility + GH recovery + ROS reduction