Side-by-side · Research reference
SS-31vsTesamorelin
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
APhase 3Reviewed9/43 cited
BFDA-ApprovedVerified27/68 cited
SS-31
Cardiolipin-binding · Mitochondrial protective
SQ · Abdomen · Once daily
Tesamorelin
GHRH Analogue · FDA-Approved
SQ · Abdomen · Once Daily
01Mechanism of Action
Parameter
SS-31
Tesamorelin
Primary target
Cardiolipin in inner mitochondrial membraneSzeto 2014
Hypothalamic GHRH receptorsEGRIFTA® (tesamorelin for inje 2010
Pathway
Cardiolipin binding → cristae stabilisation → ETC integrity → reduced ROS + preserved ATP synthesisSzeto 2014Szilagyi 2009
GHRH → Pituitary GH release → Liver IGF-1 synthesisFalutz 2007
Downstream effect
Mitochondrial bioenergetic preservation; cardio-, neuro-, and reno-protective effects in animal + clinical studiesSzeto 2014
Increased GH pulsatility, elevated IGF-1, lipolysis of visceral adipose tissueFalutz 2010
Feedback intact?
—
Yes — physiological pulsatility preserved
Origin
Synthetic tetrapeptide D-Arg-Dmt-Lys-Phe-NH₂; cell-permeable, mitochondrial-selectiveSzeto 2014
Synthetic 44-AA GHRH analogue with trans-3-hexenoic-acid modification for stabilityEGRIFTA® (tesamorelin for inje 2010
02Dosage Protocols
Parameter
SS-31
Tesamorelin
Standard dose
40 mg / day SQ (clinical trials)Szeto 2014
Anecdotal community range 5-10 mg/day. Phase 3 trials use 40 mg.
2 mg / dayEGRIFTA® (tesamorelin for inje 2010
FDA-approved protocol.
Frequency
Once daily
Once daily (morning or pre-sleep)
Aligns with natural GH pulse.
Lower / starter dose
5 mg / day (anecdotal)
1 mg / dayFalutz 2010
1 mg still produces significant IGF-1 elevation.
Evidence basis
Multiple Phase 3 trials (Barth, AMD, ischemia-reperfusion)Szeto 2014Szilagyi 2009
RCT / FDA-approvedFalutz 2007Falutz 2010
Duration
Indefinite for mitochondrial disease; cycled for healthspan use
12–52 weeks
VAT returns within months of stopping.
Reconstitution
Bacteriostatic water
Sterile water per labeling
Preserved at 2–8 °C after reconstitution.
Timing
Morning fasted preferred; pre-workout for exercise-induced mitochondrial stress
Empty stomach, pre-sleep preferred
Half-life
~3 h plasma; tissue uptake longer
~26 min (plasma)EGRIFTA® (tesamorelin for inje 2010
Modified vs native GHRH (7 min t½).
03Metabolic / Fat Loss Evidence
Parameter
SS-31
Tesamorelin
Primary fat target
—
Visceral adipose tissue (VAT) — abdominal
Effect on lean mass
—
Modest lean mass preservation / slight increase
Effect reversibility
—
VAT returns within months of stopping
Key publication
—
Falutz et al. NEJM 2007 · Falutz JCEM 2010 · FDA approval 2010Falutz 2007Falutz 2010EGRIFTA® (tesamorelin for inje 2010
04Side Effects & Safety
Parameter
SS-31
Tesamorelin
Injection site reaction
Erythema, mild pruritus
Erythema, pruritus, redness (common)
GI symptoms
Nausea (uncommon)
Nausea, diarrhea (mild, transient)
Headache
Reported in some Phase 3 trials
—
Cardiovascular
Cardio-protective in studies; no signal of harm
—
Fluid retention / Edema
—
Peripheral edema, arthralgia, carpal tunnel (GH-axis effect)
IGF-1 elevation
—
Dose-dependent; supraphysiological levels = discontinue
Cancer risk
—
Contraindicated in active malignancy (GH/IGF-1 axis); theoretical tumour growth riskEGRIFTA® (tesamorelin for inje 2010
Antibody formation
—
~50% at 26 weeks; non-neutralising in most; rare hypersensitivity (<1%)Sévigny 2018
Absolute Contraindications
SS-31
- ·Pregnancy / breastfeeding
- ·Hypersensitivity to peptide
Tesamorelin
- ·Active malignancy or history of treated cancer
- ·Pregnancy
- ·Hypersensitivity to tesamorelin or mannitol
- ·Disruption of hypothalamic-pituitary axis (trauma, tumour, radiation)
Relative Contraindications
SS-31
- ·None established
Tesamorelin
- ·Untreated diabetes (monitor HbA1c)
- ·Severe carpal tunnel syndrome
- ·Acute critical illness
05Administration Protocol
Parameter
SS-31
Tesamorelin
1. Reconstitution
Add bacteriostatic water per label. Light-protected handling.
Add 2.1 mL sterile water to 2 mg lyophilised vial. Roll gently — do not shake. Solution should be clear.
2. Injection site
SQ — abdomen or thigh. Rotate sites.
Subcutaneous — abdomen preferred. Rotate sites (avoid same spot within 2 cm). Avoid navel and waistband area.
3. Timing
Morning fasted; pre-workout for exercise-augmented mitochondrial stress.
Once daily. Preferred: evening, 2–3 hrs post-meal, before sleep — aligns with natural GH secretion pulse.
4. Storage
Lyophilised: refrigerate, light-protected. Reconstituted: refrigerate ≤30 days.
Lyophilised: room temp, light-protected. Reconstituted: refrigerate 2–8 °C, use within 21 days.
5. Needle
29–31G, 4–8 mm insulin syringe.
27–31G, 4–8 mm insulin syringe. Pinch skin, 45° angle for lean individuals.
06Stack Synergy
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
Tesamorelin
+ Ipamorelin
StrongTesamorelin (GHRH analogue) and ipamorelin (GHRP / ghrelin mimetic) act on two distinct receptor systems to amplify GH release synergistically — GHRH receptor + ghrelin receptor. This dual-axis stimulation produces a more robust, sustained GH pulse than either alone while maintaining physiological pulsatility. Ipamorelin is highly selective with minimal cortisol or prolactin elevation, making it the preferred GHRP pairing.
- Tesamorelin
- 2 mg SQ · evening
- Ipamorelin
- 200–300 mcg SQ · same injection
- Frequency
- Once daily, pre-sleep
- Primary benefit
- Maximal GH pulsatility, fat loss, recovery, sleep quality