Metabolic Peptide Dosage Protocols
Metabolic peptides and small molecules target AMPK, mitochondrial biogenesis, and cardiolipin. The category covers MOTS-c, AICAR, SLU-PP-332, and L-Carnitine derivatives.
5 protocols indexed
SLU-PP-332
SLU-PP-332 is a synthetic small-molecule pan-agonist of the estrogen-related receptors ERRα, ERRβ, and ERRγ developed at Saint Louis University by Burris, Billon, Kahn, and colleagues. ERRs are orphan nuclear receptors that control mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation; their physiological activation underlies the metabolic adaptations of endurance exercise. SLU-PP-332 binds ERRα with an EC50 of approximately 98 nM and activates ERRβ and ERRγ with EC50 values of 230 nM and 430 nM. In rodents, SLU-PP-332 increases mitochondrial function, expands fast oxidative type IIa muscle fibers, enhances running endurance, increases energy expenditure, improves glucose tolerance, and reduces fat mass without affecting food intake. It is a research compound only, not a peptide, and is not approved for human use. No published human pharmacokinetic, safety, or efficacy data exist, and dosing in animal studies typically uses 10–30 mg/kg orally or intraperitoneally.
Open Protocolarrow_forwardResearch PeptideAICAR
AICAR (5-aminoimidazole-4-carboxamide ribonucleoside), also known as acadesine, is a cell-permeable adenosine analog that is phosphorylated intracellularly to ZMP, an AMP mimetic that allosterically activates AMP-activated protein kinase (AMPK), the master cellular energy sensor. AICAR mimics several physiological consequences of endurance exercise: increased fatty acid oxidation, glucose uptake, mitochondrial biogenesis, and oxidative gene expression. The landmark Narkar et al. Cell 2008 study showed that four weeks of AICAR administration to sedentary mice increased running endurance by 44 percent. In humans, intravenous acadesine has been studied in cardiac surgery and acute myeloid leukemia at doses up to 0.1 mg/kg/min for several hours; the World Anti-Doping Agency prohibits AICAR as an exercise mimetic. AICAR is not approved for any chronic indication, and self-administered research subcutaneous doses (10–50 mg per session) lack any safety or efficacy validation in humans.
Open Protocolarrow_forwardLongevity & Metabolic SupportGlutathione
Glutathione (γ-L-glutamyl-L-cysteinyl-glycine, GSH) is an endogenous tripeptide and the body's principal intracellular antioxidant. Synthesized in two ATP-dependent steps catalyzed by glutamate-cysteine ligase and glutathione synthetase, it scavenges reactive oxygen species, conjugates electrophilic xenobiotics in Phase II hepatic detoxification, regenerates other antioxidants such as vitamins C and E, and maintains protein thiol redox status. Reduced GSH levels are associated with non-alcoholic fatty liver disease, Parkinson's disease, chronic obstructive pulmonary disease, HIV, and aging. Exogenous glutathione is administered intravenously (600–2400 mg per session, typically 1–3 times weekly), intramuscularly, intranasally (research only), or topically. Oral GSH bioavailability is low due to gastrointestinal hydrolysis, although liposomal and reduced-form preparations partially overcome this. Glutathione is not FDA-approved for any condition in the United States but is widely compounded; intravenous administration carries rare risks of bronchospasm and Stevens-Johnson syndrome.
Open Protocolarrow_forwardLongevity & Metabolic SupportL-Carnitine
L-Carnitine is a quaternary ammonium compound synthesized endogenously from lysine and methionine that serves as an obligate cofactor in long-chain fatty acid transport into mitochondria for β-oxidation. The carnitine palmitoyltransferase (CPT-1 and CPT-2) system shuttles long-chain acyl-CoA across the inner mitochondrial membrane, supplying substrate for cardiac, skeletal muscle, and hepatic ATP production. Primary and secondary carnitine deficiencies cause cardiomyopathy, skeletal myopathy, and hypoketotic hypoglycemia. Oral L-carnitine is FDA-approved for primary and secondary carnitine deficiency (Carnitor) at doses of 1000–3000 mg per day in adults. Off-label clinical uses include diabetes, fatty liver disease, peripheral artery disease, infertility, and fatigue. A meta-analysis of 37 randomized trials found 2000 mg/day maximizes weight-loss effects. Research IM/SC injection of 200–500 mg is used in performance and recovery protocols, although evidence is largely anecdotal.
Open Protocolarrow_forwardResearch PeptideMOTS-C
MOTS-c (mitochondrial open reading frame of the twelve-S ribosomal RNA type c) is a 16-amino-acid peptide encoded within the 12S rRNA gene of the mitochondrial genome and discovered by Changhan Lee, Pinchas Cohen, and colleagues at USC. Unlike all other known signaling peptides, MOTS-c is encoded by mitochondrial DNA rather than nuclear DNA, making it the founding member of a class of mitochondrial-derived peptides. In the seminal Cell Metabolism 2015 paper, MOTS-c was shown to enhance glucose utilization, activate AMPK, prevent age-dependent and diet-induced insulin resistance, and reduce diet-induced obesity in mice. Subsequent work demonstrated that exercise induces MOTS-c expression and that late-life MOTS-c treatment increases physical capacity. Research subcutaneous dosing typically uses 5–10 mg two or three times per week. MOTS-c is not FDA approved; an investigational MOTS-c analog (CB4211) for non-alcoholic fatty liver disease was studied in Phase Ib trials.
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