IGF-1 (Insulin-Like Growth Factor 1)

What it is

IGF-1 is an endogenous polypeptide that acts as the principal mediator of growth hormone (GH) signaling. It binds to the type 1 IGF receptor (IGF-1R), activating two major intracellular pathways: the phosphatidylinositol 3-kinase (PI3K)/AKT pathway and the mitogen-activated protein kinase (MAPK)/ERK pathway (PMID 34452353; PMID 45). These pathways regulate cell proliferation, differentiation, survival, and apoptosis. Approximately 98% of circulating IGF-1 is bound by six IGF-binding proteins (IGFBPs), which act as carrier proteins modulating bioavailability. IGF-1 bioactivity is further modulated by IGFBP-related proteins and local proteases such as PAPP-A, which cleave IGFBPs to increase local IGF-1 availability. IGF-1 exerts neuroprotective effects via AKT phosphorylation, participates in glucose metabolism through GLUT1 regulation, modulates immune function including antigen presentation and PD-L1 expression, and regulates skin proteoglycan synthesis and degradation. In inflammatory states, the hypothalamic-GH-IGF-1 axis is suppressed, contributing to cachexia and muscle wasting.

Class: Endogenous polypeptide growth factor / anabolic hormone; member of the insulin-like growth factor family

What it's studied for

• Growth and height promotion in children (association with height from childhood to adulthood) Human observational
  • Mendelian randomization showed a 1 SD increase in IGF-1 confers 0.09 SD taller adult height; IGF-1 levels at ages 7–8 years were positively associated with height at ages 7–17 years in ALSPAC cohort. PMID 41017432 De La Barrera B et al. J Clin Endocrinol Metab (2026)
• Biomarker for Parkinson's disease non-motor symptoms and anxiety progression Human observational
  • In 405 drug-naive early-stage PD patients, higher baseline serum IGF-1 was associated with slower progression of anxiety symptoms over 10 years (IGF-1 × time interaction: β = −0.003, p = 0.038). PMID 41905437 Chen S et al. Prog Neuropsychopharmacol Biol Psychiatry (2026)
  • Serum IGF-1 levels were significantly associated with NMSS scores, cognitive function, information processing speed, executive function, and fatigue in 129 PD patients. PMID 39467934 Gu L et al. Neurol Sci (2025)
• Biomarker for metabolic dysfunction-associated steatotic liver disease (MASLD) and cardio-kidney outcomes Human observational
  • In 214,512 UK Biobank participants over median 13-year follow-up, MASLD with lowest IGF-1 tertile had highest cardio-kidney outcome risk (aHR 1.24 [95% CI: 1.18–1.30]). PMID 42046180 Cho Y et al. Diabetes Obes Metab (2026)
  • Review of clinical, in vivo, in vitro, and ex vivo studies found decreased IGF-1 associated with MASLD progression in both children and adults; IGF-1 proposed as non-invasive biomarker. PMID 41796683 Srimanus K et al. Biochim Biophys Acta Mol Basis Dis (2026)
• Neuroprotection against arsenic-induced neuronal apoptosis In vitro only
  • In human SH-SY5Y neuroblastoma cells, IGF-1 treatment restored AKT phosphorylation, reduced pro-apoptotic markers (p53, cleaved caspase-3, PARP cleavage), and significantly decreased apoptotic cell death and DNA fragmentation induced by sodium arsenite. PMID 41534734 Elsayed N. Comp Biochem Physiol Toxicol Pharmacol (2026)
• Biomarker and pathogenic factor in fibromyalgia Human observational
  • Meta-analysis of 12 studies (512 FM patients, 308 controls): IGF-1 levels significantly lower in FM after sensitivity analysis (SMD = −0.458) and publication bias correction (SMD = −0.513); significantly lower in studies with original data (SMD = −0.458, p = 0.024) and recent publications (SMD = −0.679, p = 0.001). PMID 40153319 Lee YH, Song GG. Clin Exp Rheumatol (2025)
• Cancer biology — prostate cancer immune evasion and progression Mixed
  • IGF-1 suppresses antigen processing and presentation machinery and upregulates PD-L1 (CD274) via IGF-1R/AKT/ERK signaling in prostate cancer cells; multiplex immunofluorescence in primary PCa confirmed increased PD-L1 in patients with high serum IGF-1. PMID 41184420 Nandakumar AM et al. Sci Rep (2025)
  • In metastatic PCa (CHAARTED trial, n≈560), higher IGF-1:IGF-BP1 ratio at baseline and 6 months was associated with improved overall survival in both ADT and ADT+docetaxel groups. PMID 37671811 Ravi P et al. Endocr Relat Cancer (2023)
  • Review: elevated circulating IGF-1 associated with PCa risk; gut microbiota-derived SCFAs increase hepatic IGF-1 production promoting PCa progression. PMID 35370981 Matsushita M et al. Front Endocrinol (2022)
• Cancer biology — breast cancer (signaling, risk, and treatment effects) Mixed
  • Review: High IGF-1 and IGF-1R expression significantly associated with triple-negative breast cancer (TNBC) pathophysiology; IGF-1/IGF-1R axis identified as therapeutic target. PMID 39357179 Kumar S, Chaudhri S. Pathol Res Pract (2024)
  • Meta-analysis of RCTs: tamoxifen reduced IGF-1 levels (WMD: −14.41 µg/L, 95% CI: −24.23 to −4.60, p = 0.004) in women with breast cancer or at risk. PMID 38608792 Li X et al. Exp Gerontol (2024)
  • Longitudinal study (183 girls): higher IGF-1 during puberty related to earlier menarche, greater peak height velocity, and taller adult height — factors linked to breast cancer risk. PMID 32888770 Biro FM et al. J Adolesc Health (2021)
• Cancer biology — colorectal cancer glucose metabolism (Warburg effect) Mixed
  • Review: IGF-1 activates PI3K/Akt/mTORC and Raf/MAPK pathways, GLUT1, and key glycolytic enzymes, facilitating Warburg metabolic phenotype in colorectal cancer cells. PMID 34208601 Kasprzak A. Int J Mol Sci (2021)
• Cancer biology — hepatocellular carcinoma (HCC) prognosis and autophagy Mixed
  • In 33 HCC patients with T2DM vs. 33 without T2DM, higher IGF-1 expression was found in HCC+T2DM group and in cancer vs. paracancerous tissue; elevated IGF-1 associated with poor prognosis. In vitro: IGF-1 promoted autophagy, inhibiting apoptosis and inducing HepG2 growth/migration; wortmannin reversed these effects. PMID 35297369 Shan Y et al. Ann Hepatol (2022)
  • Pre- and postoperative IGF-1 levels closely associated with HCC recurrence after microwave ablation; lower IGF-1 correlated with recurrence. PMID 39552593 Ding S et al. Biomark Med (2024)
• Cancer protection — Laron syndrome (congenital IGF-1 deficiency) Human observational
  • Patients with Laron syndrome (congenital IGF-1 deficiency due to GH receptor defects) do not develop cancer; genome-wide profiling revealed differential expression of cell cycle, metabolic, cytokine, Jak-STAT, and PI3K-AKT signaling genes. PMID 37343154 Laron Z, Werner H. Endocr Relat Cancer (2023)
• Multiple myeloma progression In vitro only
  • IGF-1 enhanced epithelial-mesenchymal transition (EMT) in MM cells, promoting migration, invasion, and colony formation via the PI3K/Akt pathway. PMID 32142767 Peng Y et al. Life Sci (2020)
• Necrotizing enterocolitis (NEC) — intestinal protection in neonates Animal studies only
  • In mice, macrophage-derived IGF-1 promoted intestinal microvascular development and protected against experimental NEC; exogenous IGF-1 preserved intestinal microvascular density. In human NEC tissues, IGF-1-producing macrophages were decreased compared to controls. PMID 35388142 Yan X et al. Commun Biol (2022)
• Wound healing / burn injury Animal studies only
  • In a mouse scalding model, local subcutaneous administration of IGF-1-expressing placenta-derived MSCs increased wound contraction and healing rates, reduced inflammatory cytokines (TNF-α, IL-1β, IL-6), increased VEGF, and decreased TGF-β1 and collagen I/III expressions. PMID 33895582 Cheng S et al. J Surg Res (2021)
• Nerve regeneration Mixed
  • Review: IGF-1 and its isoforms (IGF-1Ea, MGF/IGF-1Eb/Ec) have proliferative and anti-apoptotic effects on neurons under hypoxia-ischemia, inflammation, and oxidative stress conditions. PMID 36503467 Sha Y et al. Curr Protein Pept Sci (2023)
• Polycystic kidney disease (ADPKD) pathogenesis and therapeutic target Animal studies only
  • In Pkd1RC/RC mice, PAPP-A (which increases local IGF-1 bioactivity) was highly induced; Pappa deficiency inhibited cyst development; a monoclonal antibody blocking PAPP-A proteolytic activity ameliorated ADPKD cystic disease in vivo and ex vivo. PMID 31990681 Kashyap S et al. JCI Insight (2020)
  • Review: Multiple indirect and direct evidence supports IGF-1 pathway involvement in ADPKD pathogenesis; PAPP-A-IGF axis identified as pharmacological target. PMID 32569826 Kashyap S et al. Cell Signal (2020)
• Acromegaly — monitoring and disease control assessment Human observational
  • In 90 acromegaly patients, GH/IGF-1 discordance rate ranged 35.6–52.2% depending on GH cutoffs used; fasting GH was a poor predictor of IGF-1 normalization (AUC 0.611–0.645). PMID 33236108 Campana C et al. J Clin Endocrinol Metab (2021)
• Effect of exercise on serum IGF-1 levels Human observational
  • Meta-analysis (21 studies): both endurance (p=0.01) and resistance exercise (p=0.003) significantly affected total serum IGF-1 but not free IGF-1; effect size greater for endurance (ES=0.81) than resistance (ES=0.46). PMID 32259791 Borba DA et al. J Phys Act Health (2020)
• Effect of metformin on IGF-1 levels Human RCT
  • Meta-analysis of 11 RCTs (569 individuals): overall non-significant decline in IGF-1 with metformin (WMD: −8.29 ng/mL, p=0.174); metformin significantly reduced IGF-1 in children with treatment duration <12 weeks (WMD: −55.40 ng/mL) but significantly increased IGF-1 in adults >18 years (WMD: +15.13 ng/mL). PMID 31816435 Yang X et al. Pharmacol Res (2020)
• Pomegranate extract and IGF-1 in older adults Human RCT
  • 72 participants aged 55–70 years: pomegranate extract (740 mg/day for 12 weeks) significantly increased serum IGF-1 levels (F=3.43, p=0.04) vs. placebo. PMID 41011500 Farhat G et al. Nutrients (2025)
• Post-exercise whey protein supplementation and IGF-1 Human RCT
  • 27 pre-menopausal women over 12 weeks of resistance + interval training: no significant change in IGF-1 with post-exercise whey protein supplementation vs. control (p=0.920); IGF-1 was not associated with any outcome measure. PMID 40573144 Murray M et al. Nutrients (2025)
• IGF-1 deficiency and vertebral fractures in beta-thalassemia major Human observational
  • In 30 adult male beta-thalassemia major patients, serum IGF-1 ≤50.0 ng/dL was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and predictive of GH deficiency (sensitivity 75.0%, specificity 100.0%). PMID 38526837 Costanzo G et al. J Endocrinol Invest (2024)
  • In 81 adult beta-thalassemia major patients, 94.4% of GHD and 93.6% of non-GHD patients had IGF-1 below reference range; mean IGF-1 SDS was significantly lower in GHD patients. PMID 35305249 Gagliardi I et al. J Endocrinol Invest (2022)
• Mild cognitive impairment biomarker Human observational
  • In 161 elderly MCI patients vs. 161 matched controls, serum IGF-1 was lower in MCI group (p<0.05); AUC for IGF-1 predicting MCI was 0.859; joint prediction with klotho yielded AUC 0.939. PMID 37599547 Cui L et al. Technol Health Care (2024)
• Schizophrenia as potential theranostic biomarker Human observational
  • In 62 remission schizophrenia, 65 treatment-resistant schizophrenia, and 62 healthy controls: IGF-1 was lower in the treatment-sensitive group vs. both treatment-resistant and healthy controls; IGF-1, LDL, and age of onset were significantly associated with treatment resistance. PMID 34116443 Yesilkaya UH et al. J Psychiatr Res (2021)
• Postoperative delirium biomarker Human observational
  • Meta-analysis (7 studies): low preoperative IGF-1 levels were significantly associated with post-operative delirium in abdominal surgical samples. PMID 34536657 Adamis D et al. Arch Gerontol Geriatr (2021)
• Androgenetic alopecia pathogenesis Human observational
  • In AGA patients, AR directly promoted miR-221 transcription, which suppressed IGF-1 expression, inactivating MAPK (dermal papilla cells) and PI3K/AKT (dermal sheath cells) pathways; miR-221 expression negatively correlated with IGF-1 in AGA patients. PMID 37496996 Li K et al. Int J Biol Sci (2023)
• Skin aging — regulation of biglycan and decorin proteoglycans In vitro only
  • IGF-1 treatment of primary human dermal fibroblasts increased biglycan and decorin protein levels by enhancing translation and reducing ADAMTS5-mediated degradation; ADAMTS5 mRNA and protein were increased in aged vs. young human skin. PMID 33573338 Lee H et al. Int J Mol Sci (2021)
• Autism spectrum disorder — serum IGF-1 alterations Human observational
  • In children aged 5–15 years, serum IGF-1 was increased in ASD vs. non-autistic controls by ELISA and correlated with age and CARS scores. PMID 35962006 Robinson-Agramonte MA et al. Sci Rep (2022)
• Polycystic ovary syndrome (PCOS) pathogenesis Mixed
  • Review: IGF-1 plays roles in PCOS pathogenesis through regulation of cell proliferation, metabolic processes, and inflammatory responses; IGF-1 participates via metabolic inflammation. PMID 38941670 Li X et al. Int Immunopharmacol (2024)
• Systemic sclerosis — biomarker for early disease Human observational
  • In 9 SSc patients, serum IGF-1, RANTES, and VEGF were significantly elevated in early/mild SSc vs. pre-clinical stage; IGF-1 and RANTES levels were significantly correlated (r=0.721). PMID 32013651 Tabata K et al. Mod Rheumatol (2021)
• Hypertension in children and adolescents Human observational
  • In 586 children/adolescents (22.3% hypertension prevalence), lowest IGF-1 quartile had adjusted OR 6.99 for hypertension vs. highest quartile (p<0.05); association more pronounced in females, ages 6–12, and those with abdominal obesity. PMID 41039295 Zhao Z et al. BMC Pediatr (2025)
• Metabolic abnormalities in children and adolescents Human observational
  • In 588 Chinese children/adolescents, higher IGF-1 (Q4: OR 0.24) and IGFBP-3 (Q4: OR 0.38) associated with lower odds of metabolic abnormalities. PMID 40538800 Zhao Z et al. Front Endocrinol (2025)
• Cabergoline therapy and IGF-1 changes in prolactinoma Human observational
  • In 127 prolactinoma patients treated with cabergoline (median follow-up 36 months), final IGF-1 levels were significantly lower than baseline (p=0.002); cumulative dose ≥60 mg and treatment duration ≥18 months predicted IGF-1 reduction (AUROC ≈0.70). PMID 41108835 Demir AN et al. Growth Horm IGF Res (2025)
• Retinal pigment epithelium metabolism and oxidative stress In vitro only
  • In ARPE-19 cells, IGF-1 favored PKM2 dimerization, reducing PKM2 activity and altering cellular energy status with reduced oxidative stress; klotho pre-treatment antagonized IGF-1 effects on mitochondrial function. PMID 39769402 Ravera S et al. Int J Mol Sci (2024)

Community-reported dosing

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.