Which peptides increase Insulin-like Growth Factor-1 (IGF-1) levels?

Peptides That Increase IGF-1 Levels

Growth hormone and growth hormone-releasing peptides (GHRPs) are the primary peptides that increase IGF-1 levels, with growth hormone exerting its anabolic effects principally through stimulation of hepatic IGF-1 production. 1

Growth Hormone (GH)

• Growth hormone is a peptide hormone secreted by the pituitary that directly stimulates hepatic production of insulin-like growth factor-1 (IGF-1). 1
• GH administration increases serum IGF-1 levels and has been shown to increase lean body mass in clinical studies, though strength improvements are less consistent. 1
• In chronic kidney disease, supraphysiological doses of recombinant human GH can overcome GH insensitivity by stimulating IGF-1 synthesis and normalizing somatomedin bioactivity. 1
• GH therapy is expensive and associated with side effects including salt and water retention, impaired glucose metabolism, and in cases of chronic excess (acromegaly), can lead to cardiac complications. 2

Growth Hormone-Releasing Peptides (GHRPs)

GHRPs represent a family of synthetic oligopeptides that indirectly increase IGF-1 by stimulating endogenous GH release. 3

Specific GHRP Compounds:

• GHRP-2, GHRP-6, and sermorelin (a GH-releasing hormone analog) administered at 100 mcg three times daily significantly increase serum IGF-1 levels. 4
• In a study of hypogonadal men on testosterone therapy, combination GHRP/sermorelin treatment increased mean IGF-1 levels from 159.5 ng/mL to 239.0 ng/mL (p < 0.0001) after an average of 134 days of treatment. 4
• Strict compliance with thrice-daily dosing is essential for achieving IGF-1 increases with GHRP therapy. 4
• GHRPs are orally active and stimulate GH secretion dose-dependently in both animals and humans, with effects comparable to intravenous peptide administration. 3
• Ipamorelin and its derivatives (such as NNC 26-0235) demonstrate high potency for GH release and have shown 10-20% oral bioavailability in animal studies. 5

Mechanism of Action:

• GHRPs stimulate GH release by acting at the pituitary level through a receptor distinct from the endogenous GH-releasing hormone (GHRH) receptor. 3
• These peptides also have specific binding sites in the hypothalamus and modulate hypothalamic GHRH and somatostatin neurons to enhance GH secretion. 3
• The combination of GHRPs with GHRH produces synergistic effects on GH release. 3

Recombinant Human IGF-1 (rhIGF-1)

• Direct administration of recombinant human IGF-1 bypasses the GH pathway and directly increases circulating IGF-1 levels. 2
• rhIGF-1 administration increases bone formation markers in adolescents and adults with anorexia nervosa. 2
• In adult women with anorexia nervosa, rhIGF-1 combined with oral estrogen led to a 2.8% significant increase in bone mineral density compared to controls. 2

Platelet-Derived Growth Factor-BB (PDGF-BB)

• PDGF-BB demonstrates synergistic effects with IGF-1 on mitogenesis of periodontal and bone precursor cells, though it does not directly increase systemic IGF-1 levels. 1
• Early clinical trials combined rhPDGF-BB (150 μg/mL) with IGF-1 for periodontal regeneration, demonstrating enhanced bone formation. 1

Important Clinical Caveats:

Factors That Reduce GHRP/GH Effectiveness:

• Concurrent use of aromatase inhibitors or tamoxifen (estrogen receptor blockade) results in smaller increases in IGF-1 levels during GHRP/sermorelin therapy. 4
• Oral estrogen peptides suppress hepatic IGF-1 production through first-pass liver metabolism, which upregulates IGF-binding proteins and reduces IGF-1 bioavailability. 2

Anabolic Steroids:

• Testosterone and anabolic steroids may increase IGF-1 indirectly through interaction with the IGF-1 system and modulation of protein synthesis pathways. 2
• Low-dose anabolic steroids increase fat-free mass through mechanisms that include modulation of the IGF-1 system and regulation of the myostatin gene. 2

Monitoring Considerations:

• IGF-1 levels must be interpreted against age-matched, sex-matched reference ranges as levels decline substantially with aging. 6
• Poorly controlled diabetes mellitus can cause falsely elevated IGF-1 levels without actual GH excess. 6
• Approximately 98% of circulating IGF-1 is bound to IGF-binding proteins (IGFBPs), which significantly affects bioavailability and assay interpretation. 7