Side-by-side · Research reference
ARA 290vsSS-31
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
APhase 2HUMAN-REVIEWED17/59 cited
BPhase 3HUMAN-REVIEWED9/43 cited
SS-31
Cardiolipin-binding · Mitochondrial protective
SQ · Abdomen · Once daily
01Mechanism of Action
Parameter
ARA 290
SS-31
Primary target
Innate repair receptor (EPO receptor / CD131 heterodimer)
Cardiolipin in inner mitochondrial membraneSzeto 2014
Pathway
EPO/CD131 → JAK2 activation → PI3K/AKT, MAPK signaling → anti-inflammatory, anti-apoptotic cascades
Cardiolipin binding → cristae stabilisation → ETC integrity → reduced ROS + preserved ATP synthesisSzeto 2014Szilagyi 2009
Downstream effect
Tissue protection, nerve fiber regeneration, suppression of inflammatory macrophage activation, altered T-cell differentiation (↑Treg, ↑Th2, ↓Th1)Liu 2014Culver 2017
Mitochondrial bioenergetic preservation; cardio-, neuro-, and reno-protective effects in animal + clinical studiesSzeto 2014
Origin
11-amino-acid sequence from EPO helix B, engineered to eliminate hematopoietic activity while retaining tissue-protective properties
Synthetic tetrapeptide D-Arg-Dmt-Lys-Phe-NH₂; cell-permeable, mitochondrial-selectiveSzeto 2014
Antibody development
Not reported in clinical trials
—
02Dosage Protocols
Parameter
ARA 290
SS-31
Standard dose (Phase 2)
4 mg / dayBrines 2015Culver 2017
Sarcoidosis SFN and diabetic neuropathy trials.
—
Frequency
Once daily
Self-administered subcutaneously.
Once daily
Duration
28 days (Phase 2)Culver 2017
Corneal nerve improvements observed by day 28.
Indefinite for mitochondrial disease; cycled for healthspan use
Evidence basis
Phase 2 RCTsCulver 2017Brines 2015
64-subject sarcoidosis trial, type 2 diabetes trial.
Multiple Phase 3 trials (Barth, AMD, ischemia-reperfusion)Szeto 2014Szilagyi 2009
Timing
Any time of day
No circadian dependence reported.
Morning fasted preferred; pre-workout for exercise-induced mitochondrial stress
Standard dose
—
40 mg / day SQ (clinical trials)Szeto 2014
Anecdotal community range 5-10 mg/day. Phase 3 trials use 40 mg.
Lower / starter dose
—
5 mg / day (anecdotal)
Reconstitution
—
Bacteriostatic water
Half-life
—
~3 h plasma; tissue uptake longer
03Metabolic / Fat Loss Evidence
Parameter
ARA 290
SS-31
Primary effect
Improved metabolic control (HbA1c, fasting glucose)Brines 2015
Secondary to neuropathy treatment; direct lipolytic effects not established.
—
HbA1c
Significant reduction vs placebo
Observed in type 2 diabetes + neuropathy trial.
—
Fasting glucose
Improved in ARA 290 group
—
Body composition
Not directly quantified
Fat loss not a primary endpoint; metabolic improvements may reflect insulin sensitivity.
—
04Side Effects & Safety
Parameter
ARA 290
SS-31
Injection site reaction
Mild, transient
Erythema, mild pruritus
Hematopoiesis
None — non-erythropoietic
Distinguishes ARA 290 from native EPO.
—
Cardiovascular
No thrombotic events or hypertension reported
Cardio-protective in studies; no signal of harm
Immunogenicity
No antibody formation reported
—
GI symptoms
—
Nausea (uncommon)
Headache
—
Reported in some Phase 3 trials
Pregnancy / OB
—
Avoid — insufficient data
Absolute Contraindications
ARA 290
- ·Hypersensitivity to ARA 290
SS-31
- ·Pregnancy / breastfeeding
- ·Hypersensitivity to peptide
Relative Contraindications
ARA 290
- ·Active malignancy (theoretical EPO-axis concern; not observed in trials)
SS-31
- ·None established
05Administration Protocol
Parameter
ARA 290
SS-31
1. Preparation
Reconstitute lyophilised powder per manufacturer instructions. Use sterile technique.
Add bacteriostatic water per label. Light-protected handling.
2. Injection site
Subcutaneous — abdomen, thigh, or upper arm. Rotate sites to avoid lipohypertrophy.
SQ — abdomen or thigh. Rotate sites.
3. Timing
Once daily, any time of day. Self-administered in Phase 2 trials.Brines 2015
Morning fasted; pre-workout for exercise-augmented mitochondrial stress.
4. Dosing
4 mg daily for 28 days (Phase 2 protocol). Duration for chronic use not established.Culver 2017
Lyophilised: refrigerate, light-protected. Reconstituted: refrigerate ≤30 days.
5. Storage
Lyophilised: store at controlled room temperature. Reconstituted: refrigerate, use within specified timeframe.
29–31G, 4–8 mm insulin syringe.
06Stack Synergy
ARA 290
+ BPC-157
ModerateARA 290 targets the innate repair receptor (EPO/CD131) for nerve regeneration and anti-inflammatory signaling, while BPC-157 promotes angiogenesis and tissue repair through distinct mechanisms (likely involving VEGF, growth hormone receptor pathways). Combined, they may address both neuroinflammation and structural tissue repair in neuropathy or injury models. No direct clinical data; mechanistic overlap in tissue protection.
- ARA 290
- 4 mg SQ · daily
- BPC-157
- 250–500 mcg SQ · daily
- Frequency
- Once daily, same or separate injections
- Primary benefit
- Nerve regeneration, pain reduction, tissue healing
SS-31
+ MOTS-c
ModerateSS-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