Side-by-side · Research reference

CJC-1295 (no DAC)vsMOTS-c

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

APhase 1Reviewed15/51 cited

BAnimal-StrongReviewed16/68 cited

CJC-1295 (no DAC)

Short-acting GHRH · No DAC variant

100 mcgPer doseTeichman 2006

~30 minHalf-lifeIonescu 2006

Phase 1Evidence levelTeichman 2006 Sigalos 2018

SQ · Pre-sleep · 1–2×/day

MOTS-c

Mitokine · Mitochondria-Encoded

5–10 mgWeekly doseLee 2015

AnimalEvidence levelLee 2015 Reynolds 2021

Min–hrsHalf-life

SQ · Variable · 2–3×/week

01Mechanism of Action

Parameter

CJC-1295 (no DAC)

MOTS-c

Primary target

Pituitary GHRH receptorTeichman 2006

Mitochondrial 12S rRNA sORF → folate-AICAR-AMPK axisLee 2015

Pathway

GHRH-R → Gαs → cAMP → PKA → GH vesicle exocytosisTeichman 2006

Folate cycle inhibition → ↑AICAR → AMPK phosphorylation → PGC-1α upregulationLee 2015 Kim 2018

Downstream effect

Pulsatile GH release matching physiological pattern; subsequent IGF-1 elevationIonescu 2006

Enhanced fatty acid oxidation, GLUT4-mediated glucose uptake, mitochondrial bioenergetics, anti-inflammationLee 2015

Feedback intact?

Yes — short pulse preserves somatostatin negative feedbackIonescu 2006

Stress-responsive, AMPK-dependent nuclear translocationKim 2018

Origin

Modified human GRF 1-29 with four substitutions (D-Ala²/Gln⁸/Ala¹⁵/Leu²⁷) for protease resistanceTeichman 2006

Endogenous 16-AA mitokine; mtDNA-encoded; declines with age; upregulated by exerciseReynolds 2021

Antibody development

Not reported in short-term studies

—

02Dosage Protocols

Parameter

CJC-1295 (no DAC)

MOTS-c

Standard dose

100 mcg per injectionTeichman 2006

Often paired with ipamorelin in same syringe.

5–10 mg / weekLee 2015

Experimental, extrapolated from animal data. No human RCT-derived dose.

Frequency

1–2× daily (pre-sleep ± morning)

2–3× per week

Short half-life may necessitate more frequent dosing for saturation.

Lower / starter dose

50 mcg per dose

2.5–5 mg / week

Recommended due to limited human data.

Evidence basis

Phase 1 (CJC-1295 with DAC); analog dataTeichman 2006 Ionescu 2006

No-DAC variant is less studied directly; PK extrapolated from native GHRH.

Animal + anecdotalLee 2015 Reynolds 2021 A 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 on / 4 off (anecdotal)

4–12 weeks (experimental)

Optimal cycle length unknown.

Reconstitution

Bacteriostatic water

Bacteriostatic water, 1–2 mL

10 mg/mL at 1 mL.

Timing

Pre-sleep + fasted preferred

Pre-workout or fasted state preferred

Activity-context amplifies AMPK response.

Half-life

~30 minIonescu 2006

Short pulse vs CJC-1295-DAC (~8 days). Choose no-DAC for pulsatile, DAC for sustained.

Minutes to hours (estimated)

Systemically unstable; native MOTS-c PK in humans not fully characterised.

03Metabolic / Fat Loss Evidence

Parameter

CJC-1295 (no DAC)

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

Insulin sensitivity

—

Reversed HFD insulin resistance in 7 days (mice)Lee 2015

Triglycerides

—

AMPK-driven FA oxidation suggests TG benefit (not directly measured)

Glucose metabolism

—

Improved glucose tolerance; GLUT4 upregulationLee 2015

Effect reversibility

—

Unknown — no long-term follow-up data

Context dependency

—

No effect in normal-chow mice; requires metabolic stressReynolds 2021

Key publication

—

Lee Cell Metab 2015 · Reynolds Nat Commun 2021 · Kim Cell Metab 2018Lee 2015 Reynolds 2021 Kim 2018

04Side Effects & Safety

Parameter

CJC-1295 (no DAC)

MOTS-c

Injection site reaction

Erythema, mild pruritus

Mild irritation (reported)

Flushing / headache

Common transient effect

—

Cortisol elevation

Minimal at standard doses

—

Prolactin elevation

Minimal

—

Glucose intolerance

Possible at high cumulative doses

Improves glucose toleranceLee 2015

IGF-1 elevation

Dose-dependent; monitor with chronic use

—

Cancer risk

Contraindicated in active malignancy (GH/IGF-1 axis)

Contradictory data — some models suggest pro-proliferative effects

Pregnancy / OB

Avoid

Avoid — insufficient safety data

Fluid retention / Edema

—

Not reported

Cardiovascular

—

Heart palpitations (anecdotal); cardiac hypertrophy reversed in diabetic rats

CNS / Neurological

—

Insomnia, headache (anecdotal reports)

GI symptoms

—

Nausea, stomach discomfort (reported)

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

CJC-1295 (no DAC)

·Active malignancy or cancer history
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

MOTS-c

·Pregnancy / breastfeeding (insufficient data)

Relative Contraindications

CJC-1295 (no DAC)

·Untreated diabetes
·Severe insulin resistance

MOTS-c

·Active cancer or cancer predisposition
·AMPK pathway deficiency (efficacy nullified)
·Use with cancer-promoting medications (theoretical)

05Administration Protocol

Parameter

CJC-1295 (no DAC)

MOTS-c

1. Reconstitution

Add 2 mL bacteriostatic water to 2 mg vial → 1 mg/mL = 100 mcg per 0.1 mL. Roll gently.

Add 1–2 mL bacteriostatic water. At 10 mg/vial, 1 mL gives 10 mg/mL concentration. Roll gently to dissolve.

2. Injection site

Subcutaneous, abdomen or thigh. Rotate sites.

Subcutaneous — abdomen, thigh, or deltoid. Rotate sites to avoid lipohypertrophy. Pinch fat layer.

3. Timing

Pre-sleep preferred. Often combined with ipamorelin in the same syringe.

Pre-workout or fasted state preferred — metabolic context amplifies AMPK response. 2–3× per week.

4. Storage

Lyophilised: room temp, protected from light. Reconstituted: refrigerate 2–8 °C, use within 30 days.

Lyophilised: room temp, protected from light. Reconstituted: refrigerate, use within 21–30 days. Short systemic stability.

5. Needle

29–31G, 4–8 mm insulin syringe.

27–31G insulin syringe. Short needle (4–6 mm) for SQ delivery. Clean technique mandatory.

06Stack Synergy

CJC-1295 (no DAC)

+ Ipamorelin

Strong

View Ipamorelin →

CJC-1295 (no DAC) and ipamorelin are the canonical "GHRH + GHRP" dual-axis stack at physiological timing. Both peak within 30 min and clear within 2 hours, producing a sharp, high-amplitude GH pulse closely resembling natural physiology. Preferred over the CJC-1295-DAC + ipamorelin stack when pulsatility (vs sustained elevation) is the goal.

CJC-1295 (no DAC): 100 mcg SQ · pre-sleep
Ipamorelin: 200–300 mcg SQ · same injection
Primary benefit: Pulsatile GH stimulation, recovery, body composition

Teichman 2006 Raun 1998

MOTS-c

+ Ipamorelin

Moderate

View Ipamorelin →

MOTS-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