Target IGF-1and/or Growth Hormone

As you will see below, IGF-1 (Insulin-Like Growth Factor), a product of Growth Hormone:

1) Appears to be a gene product you want to keep at a high level with aging.

2) However, too much IGF-1 may result in stimulating cancer cell formation, so you need to understand and balance your optimal level of IGF-1.

IGF-1 is a hormone that is similar in structure to insulin and works with Growth Hormone to reproduce and regenerate cells.

Growth Hormone, made by the pituitary gland, stimulates the liver to produce IGF-1 and IGF-1 subsequently stimulates growth in cells throughout the body, leading to growth and development (as in the womb and through adolescence), strengthening of tissues (improving bone density, building muscle), and healing (skin, bones, gut lining, etc.), depending on what the body needs.

IGF-1, Overall Health, and Longevity

Having either low or high IGF-1 increases risk of dying from all causes (1).

In a meta-analysis of twelve studies done in 2011 with 14,906 participants, the risk of dying from cardiovascular disease and cancer was increased in subjects with low as well as high IGF-1 levels (2).

The activity of IGF-I is influenced by at least six binding proteins (IGFBP). The most abundant is IGFBP-3, which binds more than 90% of IGF-1 in the circulation. Although IGF-I and IGFBP-3 are typically well correlated, there is speculative evidence that IGF-1 has an independent impact on disease risk, for example, on cancer.

When it comes to cancer, it’s probably better to err on having IGF-1 lower than higher (but not low).

When it comes to autoimmunity or chronic inflammation, it’s probably better to err on having IGF-1 higher than lower (but not high).

Benefits of IGF-1

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1) IGF-1 May Be Anti-Aging

The length of telomeres in the DNA have shown to be important predictors of longevity. IGF-1 has been shown to correlate with greater telomere length in healthy subjects of all ages (3) and in elderly men, in another study (4).

In the famous Framingham Heart Study of 525 people between the ages of 72 and 92, greater levels of IGF-1 were associated with decreased risk of dying in the next 2 years (5).

IGF-1 helps prevent age-related cognitive decline by promoting new cell growth in the brain (in rats) (6).

 

2) IGF-1 Increases Cellular Antioxidants

IGF-1 increases glutathione peroxidase, an important antioxidant enzyme (7).

It protects cells exposed to radiation, by preventing cell death and increasing the antioxidant status (8).

 

3) IGF-1 Decreases Inflammation and Autoimmunity

When IGF-1 levels are low, inflammation tends to be high (9).

In mouse models of autoimmunity and brain inflammation, administration of IGF-1 delayed disease onset; however, giving IGF-1 after the disease had developed led to enhanced worsening of the disease (10).

Allergic contact dermatitis, Multiple Sclerosis and type 1 diabetes is reduced in mice when they’re given IGF-1 (11).

Low IGF-1 levels have been documented in patients with HIV [R] and inflammatory bowel diseases (12).

Patients with chronic inflammatory diseases, such as Rheumatoid Arthritis and Lupus tend to have lower levels of circulating IGF-1 (13).

IGF-1 helps combat autoimmunity by increasing T Regulatory Cells (14).

IGF-1 also decreases MHCI gene expression (15).

In animals studies, high histamine levels in the body are associated with low IGF-1 in the blood (reduced via a histamine H1 receptor-mediated pathway). Endotoxemia reduced IGF-1 levels. (16).

4) IGF-1 Helps Brain Function

IGF-1 improves learning and memory in animal models (R, R2).

 

It speeds up mental processing in a study of 25 older men (R).

IGF-1 prevents the accumulation of amyloid plaque in the brain, in a rat model of Alzheimer’s disease (R).

In people, Alzheimer’s Disease and Dementia are associated with lower IGF-1 levels (RR2), and IGF-1 resistance accompanies insulin resistance in the brain in Alzheimer’s Disease (R),

It increases BDNF in the brain, mimicking the effects of exercise (R).

It helps motor neuron diseases like ALS  (R, R2).

It works as an anti-anxiety and anti-depressant in mouse studies(R).

Lower levels of IGF-1 are associated with depression in aged mice(R).

ALS (Amyotrophic Lateral Sclerosis) is associated with lower IGF-1 (R).

4) IGF-1 Builds Muscle and Reduces the Muscle Wasting Seen in Aging

IGF-1 is important for building muscle (R), and for reducing muscle loss in aging and disease (R).

6) IGF-1 Improves Blood Sugar Balance

Lower IGF-1 is associated with Metabolic syndrome (R).

IGF-1 infusions helped lower blood sugar, improve insulin sensitivity, and lower triglycerides in a study of Diabetes Type 2 patients (R).

People who are obese are more likely to have lower free IGF-1 (R).

7) IGF-1 Protects against Heart Disease

IGF-1 has shown to have anti-inflammatory and anti-oxidant effects on blood vesselsstabilizing existing plaque and reducing additional plaque accumulation (R).

Cardiovascular disease (coronary artery disease, fatal ischemic heart disease, ischemic stroke, congestive heart failure, as well as slower recovery after a heart attack) is associated with reduced IGF-1 (R).

Lower IGF-1 levels were associated with higher risk of stroke in a study of a Chinese population (R).

8) IGF-1 Helps Bone Density

Higher IGF-1 levels are associated with greater bone mineral density in older women (R).

We know that IGF-1 is a direct promoter of bone growth (R).

However, IGF-1’s muscle-building (anabolic) effect may also promote bone density, since increasing muscle mass, in turn, requires greater bone strength (R).

9) IGF-1 Helps Your Gut

In animal models of colitis, burns and jaundice, treatment with IGF-1 improved gut health. It stimulated mucosal DNA and protein content and drastically reduced the incidence of bacterial translocation (R, R2, R3).

In animal models of small bowel transplantation, IGF-I improved the mucosal structure and absorptive function and reduced bacterial translocation (R).

Infants with gut permeability showed faster healing times when given IGF-1 (R).

10) IGF-1 Boosts The Immune System

IGF-1 can help increase natural killer cell activity (R).

IGF-I drives B-cells to multiply (R).

11) IGF-1 Helps With Electrolyte Balance

IGF-1 has been shown to help restore fluid balance in the elderly rats (R, R2) and in humans (R).

12) IGF-1 is Good For Skin

Reviving stagnant collagen synthesis can help protect skin against aging (R).

Insulin-like growth factor-I (IGF-I) is the most potent stimulator of collagen biosynthesis and may help prevent skin aging (R).

Drawbacks of IGF-1

Because IGF-1 stimulates growth, it can have negative effects in someone who is prone to cancer.

IGF-1 exerts powerful effects on each of the key stages of cancer development.

It increases cellular proliferation, angiogenesis, and metastasis and reduces cell death (apoptosis). It also can lead to resistance to chemotherapeutic agents (R).

When it comes to cancer, not only is IGF-1 important but so is IGF-1 binding protein (IGFBP), which blocks the effects of IGF-1.

So it’s the ‘free’ levels of IGF-1 that are most important.

IGF-1 creates an environment conducive to breast cancer and resists anti-cancer drugs (RR2).

IGF-1 was shown to increase invasiveness of breast cancer (R).

A review of 17 studies found that IGF-1 is positively associated with breast cancer risk, taking levels of IGF binding protein (IGFBP3) into account, due to its effects on estrogen-sensitive tumors (R).

High IGF-1 is associated with an increased risk for prostate cancer(R).

Blood IGF-1 levels are higher in those with lung cancer than controls (R). (or maybe not (R).)

Higher IGF-1 levels in the blood are associated with colorectal cancer (R).

However, another study found that both low and high IGF-1 increased the chance of dying from cancer (R).

NOTE: Studies are unclear. Some take into account IGF-binding protein 3, and some do not. IGF-binding protein 3 (IGFBP3) is supposed to keep IGF-1 levels in the body in balance. When IGF binding protein (IGFBP) levels are low, free IGF-1 is unchecked, and can cause growth that is out of control. That’s where cancer may come in. In most cases, elevated IGF-1 is associated with a reduced cancer risk more than an elevated risk (R).

 

Increasing IGF-1

If you have low IGF-1 levels, you might want to focus a bit more on things that increase IGF-1, especially if you’re genetically predisposed to autoimmunity.

Inhibiting IGF-1

If you have high IGF-1 levels, you might want to focus a bit more on things that inhibit IGF-1, especially if you’re genetically predisposed to cancer.

  • Fasting (R), especially prolonged fasting (R)
  • Carbs – Higher dietary proportion of carbohydrates is associated with lower IGF-1 (R)
  • Protein restriction (R)
  • Calorie restriction (R)
  • Thyroid hormones – Thyroid hormones decrease IGF-1 (R).
  • Intense walking (R)
  • Legumes (R)
  • Royal jelly (R)
  • Glucosamine (R)
  • Bilberry (R),
  • Luteolin (R)
  • Curcumin (R)
  • Resveratrol (Grapes -especially the skin, mulberries, peanuts) (R). Inhibits IGF-1 in intestinal cells, reducing collagen formation that might otherwise lead to scarring and narrowing of the intestinal passageway. (Resveratrol increases IGF-1 in the brain –see below).
  • Apigenin (R, R2) –in a study of human prostate cancer.
  • Lycopene (Tomatoes, guava, rosehip, watermelon, papaya, apricot, pink grapefruit) (R)
  • EGCG (Green tea) (R)
  • Boron (fruits & vegetables, raisins, prunes, nuts, legumes) – reduces free IGF  (R)
  • Genistein (Soybeans and soy products, red clover, and Sicilian pistachio) (R)
  • Inflammation: Histamine (R)TNF-a (R), IL-6 (R), IL-1-alpha (R)….the negative effect of IL-6 on muscle function may be caused by lower IGF-1 [R].
  • Tamoxifen (R)…

Genetic Influences/IGF-1 SNPs 

SelfDecode is the best genetic analyzer and SNP decoder and will help you translate your raw 23andme data into meaningful information.

There are SNPs in the IGF1 gene:

  1. RS1019731 (IGF1) 
  2. RS2946834 (IGF1
  3. RS5742694 (IGF1)
  4. RS6214 (IGF1)
  5. RS6220 (IGF1)
  6. RS7136446 (IGF1)

There are SNPs in the IGF1R gene:

A hormone is only as good as the receptor that it binds to.

  1. RS2229765 (IGF1R)
  2. RS4966035 (IGF1R)

There are SNPs in the IGFBP3 gene (and IGFBP1):

IGFBP3 is the main binding protein to IGF-1.

  1. RS13223993 (IGFBP3)
  2. RS2132570 (IGFBP3)
  3. RS2453839 (IGFBP3)
  4. RS2471551 (IGFBP3)
  5. RS2854744 (IGFBP3)
  6. RS2854746 (IGFBP3)
  7. RS3110697 (IGFBP3)

Testing Blood IGF-1 Levels

Before you start leaning toward increasing or decreasing IGF-1, you should test it.

Check IGF-1 levels.  You should also check IGFBP3, which binds to IGF-1.  Remember, it’s the free IGF-1 that is most relevant.

With these two results, you can understand where you are with IGF-1 and what to do about it, which will depend on your personal genetics, history, and preferences.

If you have low levels, you might also want to check Growth Hormone to see if that’s what’s causing lower IGF-1.

Here is a chart you can look at to see where your blood levels of IGF-1 should fall: (R)

Age: Average Serum IGF-1 (ng/ml)
21-30 158-230
31-40 135-220
41-50 121-193
51-60 98-150
61-70 85-140
71-80 85-95
80+ 85-90

Other studies of IGF-1 ranges (United States, Brazil, European countries) came up with averages slightly higher (R, R2).

Protein makes an impact: In a study of middle-aged Americans following diets of varying protein content, low protein diets (less than 10% of calories from protein) resulted in IGF-1 levels of 190-210 ng/ml. Moderate protein (10-19%) and high protein (20% +) diets resulted in IGF-1 levels between 200 and 250 ng/ml. The IGF-1 levels of older people mirrored those of the low protein group (R).

IGF-1 Ranges and Diseases:

Breast cancer:

  • Studies showed an IGF-1 range of 170-190 in women aged 45-60 with breast cancer (R).
  • In another study, premenopausal women with IGF-1 levels over 207 were at an increased risk of breast cancer (R).

Prostate cancer:

  • Studies showed an IGF-1 range of 160-170 for men with prostate cancer around age 60 (R).
  • In another study of men with prostate cancer averaging at age 65, IGF-1 levels were around 150-170 (R).
  • In the Physicians’ Health Study, an IGF-1 over 185 raised the risk for prostate cancer (R).

Cardiovascular Disease and Cancer:

  • Higher IGF-1 (approximately 190) is associated with increased risk of cardiovascular events and deaths from cancer in elderly men (average age 75) (R).

Higher Overall Risk of Disease or Mortality:

  • IGF-1 levels are about 70-80 or lower are associated with an overall increased risk of disease or death (R).

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