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IGF-1’s Link to Cancer


The relationship between IGF-1 levels and health is somewhat complicated. Excessively low or high IGF-1 levels could lead to health problems. In adults, a high IGF-1 level is linked to accelerated aging and an increased risk of cancer and premature death.1-5 Maintaining a relatively low IGF-1 level throughout most of one’s adult life is thought to be an important factor by which centenarians are able to live that long without developing cancer.

However, low IGF-1 in the elderly is linked to frailty and disease risk as well. Adequate IGF-1 levels are required for maintenance of bone mass, muscle mass and brain function at later ages. 6-8

So to prolong our lifespan, the goal is to maintain a relatively low IGF-1 throughout most of our adult life, and then as we get into our eighties and beyond, to consume enough protein so that our IGF-1 level does not get excessively low.

It is important to pay attention to our diet, to ensure our IGF-1 levels are favorable throughout life.

How IGF-1 works in our body

IGF-1 stands for insulin-like growth factor 1. It is a hormone with a similar structure to insulin. IGF-1 is a cell growth-promoter, important during childhood, contributing to brain development and muscle and bone growth. Growth hormone (GH) from the pituitary gland stimulates IGF-1 production in the liver; IGF-1 levels peak during our teen years and twenties, and then levels decline with age.

Circulating IGF-1 is also regulated by dietary protein intake, especially animal protein. Animal protein is more biologically complete, meaning it has high levels of all essential amino acids, so it can trigger excessive body production of IGF-1, whereas plant protein does not.9-10 High-glycemic, refined carbohydrates can also raise IGF-1.11-13

Optimal IGF-1 levels

A meta-analysis analyzed ten studies on IGF-1 levels and all-cause mortality. The authors found a “U-shaped” association, meaning that IGF-1 levels on the low end and the high end of the spectrum were associated with increased risk of premature death.14

The lowest risk was at the 55th percentile of serum IGF-1, and increased in both directions for all-cause, cancer, and cardiovascular mortality.14 This data suggests that we should aim for an IGF-1 level near the lower to middle for healthy people in our age range. A few studies, primarily in European populations, have attempted to define average IGF-1 levels for healthy people in different age ranges:15-17

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

These numbers are somewhat lower than the average IGF-1 levels reported in several other studies in U.S. and European populations.

The European Prospective Investigation into Cancer and Nutrition (EPIC) study reported an average serum IGF-1 level of 200-210 ng/ml, suggesting that this is a typical level for adults on a Western diet.18 The amount of animal products consumed by most Americans drives their IGF-1 into this danger zone (above 200), increasing their risk of cancer.

Two studies comparing adults on a vegan (or raw vegan) diet (9-10 percent of calories from protein, no animal protein) to those on a Western diet (16-17 percent of calories from protein) found the Western diet average IGF-1 level of 200 ng/ml and vegan average lower than 150 ng/ml. One of these studies also evaluated IGF-1 in non-vegan endurance runners, and their average was about 175.19-20 The average age of subjects in these studies was in the mid-50s.

Low IGF-1 levels associated with an increased risk of disease or mortality are generally about 70-80 ng/ml or lower.15,21-26 Studies in elderly men (average age 75) have found increased risk of cardiovascular events and deaths from cancer in high IGF-1 groups, approximately 190 ng/ml.22-23

In the Nurses’ Health Study, premenopausal women with IGF-1 levels higher than 207 had a substantially higher risk of breast cancer.2,7 In the Physicians’ Health Study, there was an increase in prostate cancer risk once IGF-1 increased above 185 ng/ml.28

Taking all of this information into account, for most adults, keeping IGF-1 below 175 ng/ml is likely important, and below 150 ng/ml should be even more protective. Serum IGF-1 levels below 80 ng/ml may be detrimental, especially after the age of 75.

Restricting animal protein during most of one’s adult life to maintain a relatively low, but not excessively low IGF-1, is an important objective for those desiring superior health and life extension.  Protein assimilation can decline in the elderly. The use of greens, seeds and beans in the Nutritarian diet, to assure protein adequacy with aging, prevents the excessive lowering of IGF-1 in the elderly, often seen with other plant-based diets. The attention to micronutrient completeness and plant protein adequacy on a Nutritarian diet makes it the most scientifically supported diet-style to push the envelope of human longevity.

 
References
  1. Chitnis MM, Yuen JS, Protheroe AS, et al. The type 1 insulin-like growth factor receptor pathway. Clin Cancer Res 2008,14:6364-6370. 
  2. Werner H, Bruchim I. The insulin-like growth factor-I receptor as an oncogene. Arch Physiol Biochem 2009, 115:58-71.
  3. Davies M, Gupta S, Goldspink G, Winslet M. The insulin-like growth factor system and colorectal cancer: clinical and experimental evidence. Int J Colorectal Dis 2006, 21:201-208. 
  4. Sandhu MS, Dunger DB, Giovannucci EL. Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst 2002, 94:972-980. 
  5. Kaaks R. Nutrition, insulin, IGF-1 metabolism and cancer risk: a summary of epidemiological evidence. Novartis Found Symp 2004, 262:247-260; discussion 260-268.  
  6. Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging. Science 1997, 278:419-424. 
  7. Doi T, Shimada H, Makizako H, et al. Association of insulin-like growth factor-1 with mild cognitive impairment and slow gait speed. Neurobiol Aging 2015, 36:942-947. 
  8. Calvo D, Gunstad J, Miller LA, et al. Higher serum insulin-like growth factor-1 is associated with better cognitive performance in persons with mild cognitive impairment. Psychogeriatrics 2013, 13:170-174. 
  9. Thissen JP, Ketelslegers JM, Underwood LE. Nutritional regulation of the insulin-like growth factors. Endocr Rev 1994,15:80-101. 
  10. Clemmons DR, Seek MM, Underwood LE. Supplemental essential amino acids augment the somatomedin-C/insulin-like growth factor I response to refeeding after fasting. Metabolism 1985, 34:391-395. 
  11. Runchey SS, Pollak MN, Valsta LM, et al. Glycemic load effect on fasting and post-prandial serum glucose, insulin, IGF-1 and IGFBP-3 in a randomized, controlled feeding study. Eur J Clin Nutr 2012, 66:1146-1152. 
  12. Brand-Miller JC, Liu V, Petocz P, Baxter RC. The glycemic index of foods influences postprandial insulin-like growth factor-binding protein responses in lean young subjects. Am J Clin Nutr 2005, 82:350-354. 
  13. Biddinger SB, Ludwig DS. The insulin-like growth factor axis: a potential link between glycemic index and cancer. Am J Clin Nutr 2005, 82:277-278. 
  14. Burgers AM, Biermasz NR, Schoones JW, et al. Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality. J Clin Endocrinol Metab 2011, 96:2912-2920. 
  15. Ranke MB, Osterziel KJ, Schweizer R, et al. Reference levels of insulin-like growth factor I in the serum of healthy adults: comparison of four immunoassays. Clin Chem Lab Med 2003, 41:1329-1334. 
  16. Bidlingmaier M, Friedrich N, Emeny RT, et al. Reference intervals for insulin-like growth factor-1 (igf-i) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations. J Clin Endocrinol Metab 2014, 99:1712-1721. 
  17. Brabant G, von zur Muhlen A, Wuster C, et al. Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res 2003, 60:53-60. 
  18. Crowe FL, Key TJ, Allen NE, et al. The association between diet and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomarkers Prev 2009,18:1333-1340. 
  19. Fontana L, Klein S, Holloszy JO. Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk. Am J Clin Nutr 2006, 84:1456-1462. 
  20. Fontana L, Weiss EP, Villareal DT, et al. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 2008, 7:681-687. 
  21. Friedrich N, Haring R, Nauck M, et al. Mortality and serum insulin-like growth factor (IGF)-I and IGF binding protein 3 concentrations. J Clin Endocrinol Metab 2009, 94:1732-1739. 
  22. Carlzon D, Svensson J, Petzold M, et al. Both low and high serum IGF-1 levels associate with increased risk of cardiovascular events in elderly men. J Clin Endocrinol Metab 2014, 99:E2308-2316. 
  23. Svensson J, Carlzon D, Petzold M, et al. Both low and high serum IGF-I levels associate with cancer mortality in older men. J Clin Endocrinol Metab 2012, 97:4623-4630. . 
  24. van Bunderen CC, van Nieuwpoort IC, van Schoor NM, et al. The Association of Serum Insulin-Like Growth Factor-I with Mortality, Cardiovascular Disease, and Cancer in the Elderly: A Population-Based Study. J Clin Endocrinol Metab 2010. 
  25. Arai Y, Takayama M, Gondo Y, et al. Adipose endocrine function, insulin-like growth factor-1 axis, and exceptional survival beyond 100 years of age. J Gerontol A Biol Sci Med Sci 2008, 63:1209-1218. 
  26. Johnsen SP, Hundborg HH, Sorensen HT, et al. Insulin-like growth factor (IGF) I, -II, and IGF binding protein-3 and risk of ischemic stroke. J Clin Endocrinol Metab 2005, 90:5937-5941. 
  27. Hankinson SE, Willett WC, Colditz GA, et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 1998, 351:1393-1396. 
  28. Chan JM, Stampfer MJ, Giovannucci E, et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 1998, 279:563-566.
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