Understanding IGF-1: The Anabolic Growth Factor

IGF-1 (insulin-like growth factor 1) is the hormone that carries out many of growth hormone's effects on muscle, bone and tissue repair. It is made mainly in the liver in response to growth hormone, it declines with age, and it is one of the most useful labs for assessing the growth hormone axis. But IGF-1 is a double-edged signal: too little is linked to frailty, and too much is linked to disease, so balance matters more than maximizing it.

That balance is the central theme of how I think about IGF-1 in longevity medicine.

What IGF-1 Does

IGF-1 is a small protein hormone with a structure similar to insulin. Its main jobs include:

• Muscle maintenance and growth, by stimulating protein synthesis through the PI3K–Akt–mTOR pathway
• Bone formation, including during childhood growth and adult bone remodeling
• Tissue repair, supporting cell survival and regeneration after injury
• Glucose handling, with mild insulin-like effects

Growth hormone is released by the pituitary in pulses, mostly during deep sleep, and is cleared from the blood quickly. IGF-1, by contrast, is stable in the bloodstream because most of it is bound to carrier proteins, especially IGFBP-3. That is why we measure IGF-1 rather than random growth hormone levels to assess the axis.

How IGF-1 Changes With Age

IGF-1 rises through childhood, peaks in adolescence, and then gradually declines through adulthood. This decline, sometimes called "somatopause," parallels some age-related changes in muscle mass, body composition and recovery. It is tempting to conclude that restoring youthful IGF-1 would reverse those changes. The evidence does not support that simple conclusion.

Why More IGF-1 Is Not Always Better

Several lines of evidence argue for moderation:

• Mortality looks U-shaped. A 2011 meta-analysis of observational studies found that both low and high circulating IGF-1 levels were associated with higher all-cause mortality. A 2022 meta-analysis reached a similar conclusion.
• Cancer associations. Higher IGF-1 has been linked in observational research to higher risk of some cancers. IGF-1 promotes cell growth and survival, which is helpful for repair and potentially unhelpful for abnormal cells.
• Natural experiments. People with a genetic form of growth hormone insensitivity, who have very low IGF-1, have been reported to have unusually low rates of cancer and diabetes, although they have other health problems.
• Animal longevity studies. In several species, reduced growth hormone and IGF-1 signaling is associated with longer lifespan.

None of this proves that higher IGF-1 causes disease in a given person. It does mean that pushing IGF-1 to the top of the range, or above it, is not a sensible longevity goal.

How to Interpret an IGF-1 Lab

An IGF-1 result only makes sense in context. Before drawing conclusions, I consider:

• Age- and sex-specific ranges, which differ significantly and vary by laboratory and assay
• Nutrition, because fasting, calorie restriction and low protein intake lower IGF-1
• Liver health, since the liver produces most circulating IGF-1
• Thyroid status and diabetes control, both of which affect the axis
• Oral estrogen, which can lower IGF-1
• Sleep, because most growth hormone is released during deep sleep

A truly low IGF-1 may point to growth hormone deficiency, which needs a proper endocrine evaluation. A high IGF-1 without an obvious reason may need evaluation for excess growth hormone. Both are reasons to investigate, not to supplement. See lab testing before longevity or peptide discussions.

What Raises IGF-1

Foundations first. Adequate protein intake, resistance training, healthy body composition and good sleep all support a healthy growth hormone axis. The connection with sleep is direct; see sleep architecture and hormonal restoration.

Prescription options. Growth hormone itself is FDA-approved for specific deficiency states. Tesamorelin is FDA-approved for visceral fat in HIV lipodystrophy and raises IGF-1 while preserving the body's feedback loops. Mecasermin is an FDA-approved IGF-1 drug for severe primary IGF-1 deficiency, a rare condition.

Investigational secretagogues. Compounds such as CJC-1295, ipamorelin and MK-677 raise growth hormone and IGF-1, but they are not FDA-approved, and FDA's advisory committee voted against adding them to the compounding bulks list in 2024.

A Specific Caution About IGF-1 LR3

IGF-1 LR3 is an engineered IGF-1 analog designed to escape its binding proteins, which makes it far more potent and longer-lasting than natural IGF-1. It was developed as a cell-culture reagent. There are no published human clinical trials. Its insulin-like action can cause low blood sugar, and because it directly stimulates cell growth, it raises theoretical concerns about tumor promotion. It is not FDA-approved for human use and is prohibited in sport.

How I Approach IGF-1 at Laeeq M.D.

When IGF-1 comes up, I look at the full picture: IGF-1 alongside fasting glucose, HbA1c, fasting insulin, lipids, thyroid function, body composition, sleep quality and age-appropriate cancer screening. If there is a reason to adjust the axis, we discuss the options with the strongest evidence and clear regulatory standing, and any dosing is individualized after evaluation and labs.

Sources

• Burgers AMG, et al. Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality. Journal of Clinical Endocrinology & Metabolism, 2011. https://boris.unibe.ch/7309
• Association between IGF-1 levels ranges and all-cause mortality: A meta-analysis. Aging Cell, 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC8844108/

Book a Consultation

If you want to understand your IGF-1 and growth hormone axis in the context of your overall health, Dr. Laeeq offers 60-minute consultations, virtually or in Reston, VA, for patients across Virginia, Maryland, Florida, Texas, California, Pennsylvania and Tennessee. You can book a consultation here.

This article is for educational purposes and is not medical advice. Discuss any treatment with a licensed physician who knows your history.