Side-by-side · Research reference

5-Amino-1MQvsSS-31

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongDraft8/38 cited

BPhase 3Reviewed9/43 cited

5-Amino-1MQ

NNMT inhibitor · Methylation / SAM modulation

100–200 mgDaily dose (oral)Neelakantan 2018

AnimalEvidence levelNeelakantan 2018

HoursHalf-life (est)

Oral · Once daily fasted

SS-31

Cardiolipin-binding · Mitochondrial protective

40 mgDaily doseSzeto 2014

Phase 3Evidence levelSzilagyi 2009 Szeto 2014

~3 hrHalf-life

SQ · Abdomen · Once daily

01Mechanism of Action

Parameter

5-Amino-1MQ

SS-31

Primary target

Nicotinamide N-methyltransferase (NNMT)Neelakantan 2018

Cardiolipin in inner mitochondrial membraneSzeto 2014

Pathway

NNMT inhibition → preserved cellular SAM + NAD⁺ → restored methylation balance + ↑ thermogenic gene expressionNeelakantan 2018

Cardiolipin binding → cristae stabilisation → ETC integrity → reduced ROS + preserved ATP synthesisSzeto 2014 Szilagyi 2009

Downstream effect

Reversal of HFD-induced obesity in murine models; improved metabolic profileNeelakantan 2018

Mitochondrial bioenergetic preservation; cardio-, neuro-, and reno-protective effects in animal + clinical studiesSzeto 2014

Feedback intact?

—

Origin

Selective small-molecule inhibitor designed in academic medicinal chemistry programsNeelakantan 2018

Synthetic tetrapeptide D-Arg-Dmt-Lys-Phe-NH₂; cell-permeable, mitochondrial-selectiveSzeto 2014

Antibody development

—

02Dosage Protocols

Parameter

5-Amino-1MQ

SS-31

Standard dose

100–200 mg / day oralNeelakantan 2018

Anecdotal community range; murine doses scaled.

40 mg / day SQ (clinical trials)Szeto 2014

Anecdotal community range 5-10 mg/day. Phase 3 trials use 40 mg.

Frequency

Once daily, fasted

Once daily

Lower / starter dose

50 mg / day

5 mg / day (anecdotal)

Evidence basis

Animal-strong; no human RCT dataNeelakantan 2018

Multiple Phase 3 trials (Barth, AMD, ischemia-reperfusion)Szeto 2014 Szilagyi 2009

Duration

8–12 weeks per cycle

Indefinite for mitochondrial disease; cycled for healthspan use

Form

Oral capsule

—

Timing

Morning fasted preferred

Morning fasted preferred; pre-workout for exercise-induced mitochondrial stress

Half-life

Hours (estimated; no human PK published)

~3 h plasma; tissue uptake longer

Reconstitution

—

Bacteriostatic water

04Side Effects & Safety

Parameter

5-Amino-1MQ

SS-31

GI symptoms

Mild nausea (anecdotal)

Nausea (uncommon)

Methylation disruption

Theoretical risk if NNMT is over-inhibited (B vitamin metabolism)

—

Long-term safety

Unknown — no human trials

Phase 3 data over 24+ months; no major safety signalsSzeto 2014

Cancer risk

Unclear — NNMT also studied in oncology contexts

—

Pregnancy / OB

Avoid

Avoid — insufficient data

Drug interactions

Theoretical with niacin / B-vitamin supplements

—

Injection site reaction

—

Erythema, mild pruritus

Headache

—

Reported in some Phase 3 trials

Cardiovascular

—

Cardio-protective in studies; no signal of harm

Absolute Contraindications

5-Amino-1MQ

·Pregnancy / breastfeeding
·Active malignancy

SS-31

·Pregnancy / breastfeeding
·Hypersensitivity to peptide

Relative Contraindications

5-Amino-1MQ

·Methylation-sensitive conditions (MTHFR mutation)
·Concurrent niacin / NAD+ precursor supplementation (theoretical interference)

SS-31

·None established

05Administration Protocol

Parameter

5-Amino-1MQ

SS-31

1. Form

Oral capsule. No injection.

Add bacteriostatic water per label. Light-protected handling.

2. Administration

Take with water, fasted preferred.

SQ — abdomen or thigh. Rotate sites.

3. Timing

Morning fasted.

Morning fasted; pre-workout for exercise-augmented mitochondrial stress.

4. Storage

Room temp ≤25 °C, dry place.

Lyophilised: refrigerate, light-protected. Reconstituted: refrigerate ≤30 days.

5. Caveat

Monitor B-vitamin status with chronic use.

29–31G, 4–8 mm insulin syringe.

06Stack Synergy

5-Amino-1MQ

— no documented stacks

SS-31

+ MOTS-c

Moderate

View MOTS-c →

SS-31 and MOTS-c address mitochondrial decline through complementary axes. SS-31 protects existing mitochondrial structure (cardiolipin binding, cristae stabilisation). MOTS-c upregulates AMPK/PGC-1α, triggering biogenesis of new mitochondria. Together they pair preservation with renewal — anecdotally favoured in healthspan and post-cardio-event recovery protocols.

SS-31: 5–10 mg SQ · daily morning
MOTS-c: 5 mg SQ · 2× per week pre-workout
Primary benefit: Mitochondrial preservation + biogenesis