Your Trusted Brand for Over 35 Years

Life Extension Magazine

<< Back to June 2016

The Insulin/Cancer Connection

June 2016

By Miles Mueller

The Insulin/Cancer Connection  

Most people recognize insulin as a beneficial hormone. It helps remove sugar (glucose) from the blood into cells where it is used to power energy or is stored as surplus fat.

For years, Life Extension® has discussed the role of excess insulin as a culprit involved in metabolic syndrome, which increases degenerative disease risk. In particular, high levels of insulin are now recognized as important contributors to the development and progression of many kinds of cancer.1-3

How has such a vital, natural hormone been converted from life-supporting friend to deadly foe?

The answer lies with the nation’s love affair with calories, particularly those derived from simple sugars and refined carbohydrates. Americans eat so many of these dangerous foods that 50% are overweight, 30% are obese, and 10% already have type II diabetes.2

Studies in the past decade have revealed a close connection between body size, type II diabetes, and many cancers.2,3 For example, consuming a diet rich in readily digested sugars and carbohydrates increases the risk of developing the most common form of breast cancer by 36% to 41%.4

A consistent finding across a broad spectrum of common malignancies reveals that higher blood insulin, often caused by chronically elevated blood glucose, results in increased cancer risk.

For example, prostate cancer incidence is 2.55-fold greater in men with the highest blood insulin levels.5

The Emerging Connection between Obesity, Insulin, and Cancer

The Emerging Connection between Obesity, Insulin, and Cancer  

As people gain weight, their fat cells begin to pour out cytokines that generate inflammation throughout the body.3,6 This leads to the phenomenon called “insulin resistance,” in which cells lose their ability to move glucose from the blood and into cells under the influence of normal blood levels of insulin.3 As a result, sugar levels rise, triggering further increases in insulin release from the pancreas. Insulin-resistant cells cannot respond, leading to still higher glucose and higher insulin levels in a vicious cycle.2

Eventually, a state of type II diabetes develops, but elevated insulin levels are found in a very large number of people not yet diagnosed with the disease.7,8 And that’s dangerous.

Because insulin is a growth factor, high insulin levels in cells trigger more rapid cell division, while elevated sugar and fat levels provide more metabolic fuel.3,4 Along the way, some cells lose control of their DNA regulatory genes, which is the hallmark of malignancy. This sequence of events is now thought to contribute to the promotion of cancer, at least in colon cells and probably in those throughout the body.3

Research Documents Insulin’s Role in Cancer Models

Diabetes and resulting elevated insulin levels are associated with increased risk of many kinds of cancer, as well as with development of more aggressive and metastatic cancers that carry a grim prognosis.9,10 Mechanisms for this deadly trend have emerged from laboratories around the world in just the past few years.

One of the most fundamental pathologies recently elucidated is damage to DNA, often the first step in cancer development. Even very tiny amounts of insulin, applied a single time to cell cultures, generated sufficient toxic oxidative stress to damage DNA strands.10,11 Prolonging exposure for six days reduced the concentration of insulin required to induce such damage by a factor of 10, demonstrating the extreme risks of chronically elevated insulin in the body.11

As a growth factor, insulin naturally stimulates cell growth. But too much insulin results in over-stimulation once a cancer cell has emerged, promoting proliferation, migration, and invasiveness of cancer cells by means of multiple fundamental biochemical signaling pathways.9,12

A vivid demonstration of the cancer-promoting effects of insulin comes from a study of mice that had been injected with colon cancer cells and then fed either a normal or a high-calorie diet. Tumors in the high-calorie group grew to twice the size of those in the normal group in just 17 days.13 The high-calorie-diet animals had high levels of insulin and other growth-promoting molecules, demonstrating a close connection between insulin and cancer growth rate.

Human Studies Show Dangers of Elevated Insulin

Coming atop the most recent laboratory studies are a number of human studies that emphasize the essential role of insulin in promoting cancers, making this an area of fertile interest among oncologists and prevention experts.

Insulin levels have been implicated in at least seven of the most common human malignancies.

Colorectal cancer remains the second cause of cancer death in the US among men and women combined.14 Elevated insulin levels are a risk factor for these lower bowel tumors.15,16 Ethnic groups with low insulin sensitivity, even absent obesity, are known to have higher rates of colorectal cancers.16

A study involving patients who underwent both routine colonoscopy exams and fasting insulin measurements found that insulin levels raise the risk of having precancerous growths called adenomas by 17% to 42%, with higher risk associated with higher levels.17

Gastric (stomach) cancer risk is 69% higher for people with blood insulin levels in the middle third, compared with those in the bottom third of results, and 101% higher in those with the top one-third of insulin levels.18

Cancers of the female reproductive system seem especially sensitive to elevated insulin levels. For example, women with higher insulin levels are at a 2- to 3-fold increased risk for breast cancer, compared to those with lower levels.19 Similarly, risk for endometrial (uterine lining) cancer rises dramatically with elevated insulin.20 Risk increases with higher insulin levels almost 10-fold for early premalignant changes in endometrial cells, 8.5-fold for later premalignant changes, 18-fold for true precancerous lesions, and a shocking 45-fold for type I endometrial cancer.21 Elevated serum insulin levels are also associated with increased risk for ovarian cancer.22

Prostate cancer risk is also closely associated with insulin levels. Men with the highest blood insulin levels in one study showed a 2.55-fold increased risk of malignancy compared with those having the lowest levels.5 And men with the highest level of insulin had a 5.62-fold increase in the risk of having locally advanced tumors than those with lower levels, while the most insulin-resistant subjects’ risk of advanced cancer was more than 3-fold increased.23

Liver cancer has multiple triggers, including infection with hepatitis viruses. Among people infected with hepatitis B virus, those with the highest insulin levels have an approximate 2.4-fold increase in the risk of developing liver cancer.24

 
Huge Reductions in Insulin Levels with Popular Dietary Supplements

Huge Reductions in Insulin Levels with Popular Dietary Supplements

Resveratrol

47% reduction29

Omega-3

34% reduction30

Green tea

22% reduction62

Ginseng

13% reduction63

 

Supplements May Reduce Blood Insulin Levels

Several nutrients have emerged showing promise in reducing insulin levels and/or increasing insulin sensitivity, which lowers glucose and insulin blood levels.

The most prominent of these are resveratrol,25-29 fish oil rich in the omega-3 fats eicosapentaenoic and docosahexaenoic acids (EPA and DHA),30-33 green tea extracts,34-36 and ginseng extract.37

Metformin, a prescription antidiabetic drug, is also strongly associated with reduced cancer risk, and lowers insulin levels as a direct part of its actions.2,13,38,39

Additional Ways to Help Control Insulin Levels
Additional Ways to Help Control Insulin Levels

Nutrient

Impact

L-arabinose40-42

Lowers insulin levels; reduces insulin resistance

Chromium43-47

Enhances insulin sensitivity; lowers insulin levels

Coffee48-51

Improves insulin resistance; IGF-1 levels are
lower in women coffee drinkers

Phaseolus vulgaris
(white kidney bean)
and other legume extracts52-55

Lowers insulin levels

Phloridzin56-58

Normalizes glucose tolerance and insulin sensitivity

Sorghum59-61

Improves insulin sensitivity; lowers insulin levels

Summary

Consuming a Western diet high in sugars and carbohydrates produces up to a 41% increase in the risk of developing the most common kind of breast cancer. Stomach, prostate, liver, and reproductive cancers are also at an increased risk. Natural supplements may help reduce blood insulin levels, especially fish oil, green tea extracts, and resveratrol. Metformin, of course, is also strongly associated with lowering insulin levels, thereby reducing these cancer risks.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

References

  1. Fierz Y, Novosyadlyy R, Vijayakumar A, et al. Insulin-sensitizing therapy attenuates type 2 diabetes-mediated mammary tumor progression. Diabetes. 2010;59(3):686-93.
  2. Bao B, Wang Z, Li Y, et al. The complexities of obesity and diabetes with the development and progression of pancreatic cancer. Biochim Biophys Acta. 2011;1815(2):135-46.
  3. Gunter MJ, Leitzmann MF. Obesity and colorectal cancer: epidemiology, mechanisms and candidate genes. J Nutr Biochem. 2006;17(3):145-56.
  4. Romieu I, Ferrari P, Rinaldi S, et al. Dietary glycemic index and glycemic load and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Am J Clin Nutr. 2012;96(2):345-55.
  5. Pandeya DR, Mittal A, Sathian B, et al. Role of hyperinsulinemia in increased risk of prostate cancer: a case control study from Kathmandu Valley. Asian Pac J Cancer Prev. 2014;15(2):1031-3.
  6. Khan S, Shukla S, Sinha S, et al. Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets. Cytokine Growth Factor Rev. 2013;24(6):503-13.
  7. Nichols GA, Hillier TA, Brown JB. Progression from newly acquired impaired fasting glusose to type 2 diabetes. Diabetes Care. 2007;30(2):228-33.
  8. Barr EL, Zimmet PZ, Welborn TA, et al. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation. 2007;116(2):151-7.
  9. De Marco P, Romeo E, Vivacqua A, et al. GPER1 is regulated by insulin in cancer cells and cancer-associated fibroblasts. Endocr Relat Cancer. 2014;21(5):739-53.
  10. Othman EM, Hintzsche H, Stopper H. Signaling steps in the induction of genomic damage by insulin in colon and kidney cells. Free Radic Biol Med. 2014;68:247-57.
  11. Othman EM, Leyh A, Stopper H. Insulin mediated DNA damage in mammalian colon cells and human lymphocytes in vitro. Mutat Res. 2013;745-746:34-9.
  12. Bishop EA, Lightfoot S, Thavathiru E, et al. Insulin exerts direct effects on carcinogenic transformation of human endometrial organotypic cultures. Cancer Invest. 2014;32(3):63-70.
  13. Algire C, Amrein L, Zakikhani M, et al. Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase. Endocr Relat Cancer. 2010;17(2):351-60.
  14. Available at: http://www.cancer.org/cancer/colonandrectumcancer/detailedguide/colorectal-cancer-key-statistics. Accessed February 29, 2016.
  15. Jiang B, Zhang X, Du LL, et al. Possible roles of insulin, IGF-1 and IGFBPs in initiation and progression of colorectal cancer. World J Gastroenterol. 2014;20(6):1608-13.
  16. Tsai CJ, Giovannucci EL. Hyperinsulinemia, insulin resistance, vitamin D, and colorectal cancer among whites and African Americans. Dig Dis Sci. 2012;57(10):2497-503.
  17. Kim EH, Kim HK, Bae SJ, et al. Fasting serum insulin levels and insulin resistance are associated with colorectal adenoma in Koreans. J Diabetes Investig. 2014;5(3): 297-304.
  18. Hidaka A, Sasazuki S, Goto A, et al. Plasma insulin, C-peptide and blood glucose and the risk of gastric cancer: the Japan Public Health Center-based prospective study. Int J Cancer. 2015;136(6):1402-10.
  19. Kabat GC, Kim M, Caan BJ, et al. Repeated measures of serum glucose and insulin in relation to postmenopausal breast cancer. Int J Cancer. 2009;125(11):2704-10.
  20. Shao Y, Cheng S, Hou J, et al. Insulin is an important risk factor of endometrial cancer among premenopausal women: a case-control study in China. Tumour Biol. 2015.
  21. Shan W, Ning C, Luo X, et al. Hyperinsulinemia is associated with endometrial hyperplasia and disordered proliferative endometrium: a prospective cross-sectional study. Gynecol Oncol. 2014; 132(3):606-10.
  22. Otokozawa S, Tanaka R, Akasaka H, et al. Associations of serum isoflavone, adiponectin and insulin levels with risk for epithelial ovarian cancer: results of a case-control study. Asian Pac J Cancer Prev. 2015;16(12):4987-91.
  23. Yun SJ, Min BD, Kang HW, et al. Elevated insulin and insulin resistance are associated with the advanced pathological stage of prostate cancer in Korean population. J Korean Med Sci. 2012;27(9):1079-84.
  24. Chao LT, Wu CF, Sung FY, et al. Insulin, glucose and hepatocellular carcinoma risk in male hepatitis B carriers: results from 17-year follow-up of a population-based cohort. Carcinogenesis. 2011;32(6):876-81.
  25. Cabello E, Garrido P, Moran J, et al. Effects of resveratrol on ovarian response to controlled ovarian hyperstimulationin ob/ob mice. Fertil Steril. 2015;103(2): 570-9.e1.
  26. Ikuta T, Saito S, Tani H, et al. Resveratrol derivative-rich melinjo (Gnetum gnemon L.) seed extract improves obesity and survival of C57BL/6 mice fed a high-fat diet. Biosci Biotechnol Biochem. 2015;79(12):2044-9.
  27. Szkudelska K, Szkudelski T. Resveratrol, obesity and diabetes. Eur J Pharmacol. 2010;635(1-3):1-8.
  28. Etxeberria U, Arias N, Boque N, et al. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. J Nutr Biochem. 2015;26(6):651-60.
  29. Movahed A, Nabipour I, Lieben Louis X, et al. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med. 2013;2013:851267
  30. Dunn SL, Siu W, Freund J, et al. The effect of a lifestyle intervention on metabolic health in young women. Diabetes Metab Syndr Obes. 2014;7:437-44.
  31. Freire TO, Boulhosa RS, Oliveira LP, et al. n-3 polyunsaturated fatty acid supplementation reduces insulin resistance in hepatitis C virus infected patients: a randomised controlled trial. J Hum Nutr Diet. 2015.
  32. Asemi Z, Soleimani A, Bahmani F, et al. Effect of the omega-3 fatty acid plus vitamin E supplementation on subjective global assessment score, glucose metabolism and lipid concentrations in chronic hemodialysis patients. Mol Nutr Food Res. 2015.
  33. Gupta SP, Mittal A, Sathian B, et al. Elevated serum insulin is an independent risk factor for hepatocellular carcinoma: a case control study from Nepal. Asian Pac J Cancer Prev. 2013;14(12):7331-3.
  34. Dostal AM, Samavat H, Espejo L, et al. Green tea extract and catechol-o-methyltransferase genotype modify fasting serum insulin and plasma adiponectin doncentrations in a randomized controlled trial of overweight and obese postmenopausal women. J Nutr. 2015.
  35. Mozaffari-Khosravi H, Ahadi Z, Fallah Tafti M. The effect of green tea versus sour tea on insulin resistance, lipids profiles and oxidative stress in patients with type 2 diabetes mellitus: a randomized clinical trial. Iran J Med Sci. 2014;39(5):424-32.
  36. Sae-Tan S, Rogers CJ, Lambert JD. Voluntary exercise and green tea enhance the expression of genes related to energy utilization and attenuate metabolic syndrome in high fat fed mice. Mol Nutr Food Res. 2014;58(5):1156-9.
  37. Seo E, Kim S, Lee SJ, et al. Ginseng berry extract supplementation improves age-related decline of insulin signaling in mice. Nutrients. 2015;7(4):3038-53.
  38. Pollak MN. Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov. 2012;2(9):778-90.
  39. Laskov I, Drudi L, Beauchamp MC, et al. Anti-diabetic doses of metformin decrease proliferation markers in tumors of patients with endometrial cancer. Gynecol Oncol. 2014;134(3):607-14.
  40. Kaats GR, Keith SC, Keith PL, et al. A combination of l-arabinose and chromium lowers circulating glucose and insulin levels after an acute oral sucrose challenge. Nutr J. 2011;10:42.
  41. Preuss HG, Echard B, Bagchi D, et al. Comparing effects of carbohydrate (CHO) blockers and trivalent chromium on CHO-induced insulin resistance and elevated blood pressure in rats. J Am Coll Nutr. 2013;32(1):58-65.
  42. Shibanuma K, Degawa Y, Houda K. Determination of the transient period of the EIS complex and investigation of the suppression of blood glucose levels by L-arabinose in healthy adults. Eur J Nutr. 2011;50(6):447-53.
  43. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.
  44. Evock-Clover CM, Polansky MM, Anderson RA, et al. Dietary chromium supplementation with or without somatotropin treatment alters serum hormones and metabolites in growing pigs without affecting growth performance. J Nutr. 1993;123(9):1504-12.
  45. Frauchiger MT, Wenk C, Colombani PC. Effects of acute chromium supplementation on postprandial metabolism in healthy young men. J Am Coll Nutr. 2004;23(4):351-7.
  46. Sharma S, Agrawal RP, Choudhary M, et al. Beneficial effect of chromium supplementation on glucose, HbA1C and lipid variables in individuals with newly onset type-2 diabetes. J Trace Elem Med Biol. 2011;25(3):149-53.
  47. Wang ZQ, Qin J, Martin J, et al. Phenotype of subjects with type 2 diabetes mellitus may determine clinical response to chromium supplementation. Metabolism. 2007;56(12):1652-5.
  48. Ho L, Varghese M, Wang J, et al. Dietary supplementation with decaffeinated green coffee improves diet-induced insulin resistance and brain energy metabolism in mice. Nutr Neurosci. 2012;15(1):37-45.
  49. Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, et al. Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin. Clin Endocrinol (Oxf). 1994;41(3):351-7.
  50. Lecoultre V, Carrel G, Egli L, et al. Coffee consumption attenuates short-term fructose-induced liver insulin resistance in healthy men. Am J Clin Nutr. 2014;99(2):268-75.
  51. Song SJ, Choi S, Park T. Decaffeinated green coffee bean extract attenuates diet-induced obesity and insulin resistance in mice. Evid Based Complement Alternat Med. 2014;2014:718379.
  52. Martinez JA, Marcos R, Macarulla MT, et al. Growth, hormonal status and protein turnover in rats fed on a diet containing peas (Pisum sativum L.) as the source of protein. Plant Foods Hum Nutr. 1995;47(3):211-20.
  53. Nilsson A, Johansson E, Ekstrom L, et al. Effects of a brown beans evening meal on metabolic risk markers and appetite regulating hormones at a subsequent standardized breakfast: a randomized cross-over study. PLoS One. 2013;8(4):e59985.
  54. Obiro WC, Zhang T, Jiang B. The nutraceutical role of the Phaseolus vulgaris alpha-amylase inhibitor. Br J Nutr. 2008;100(1):1-12.
  55. Spadafranca A, Rinelli S, Riva A, et al. Phaseolus vulgaris extract affects glycometabolic and appetite control in healthy human subjects. Br J Nutr. 2013;109(10):1789-95.
  56. Simonyi G. New possibility in the oralglucose lowering treatment of type 2 diabetes mellitus: sodium-glucose co-transporter-2 inhibitors. Orv Hetil. 2012;153(18):695-701.
  57. Zhang S, Zhu M, Shen D. Experimental study on the treatment of diabetes by phloridzin in rats. J Tongji Med Univ. 1998;18(2):105-7, 18.
  58. Zhao H, Yakar S, Gavrilova O, et al. Phloridzin improves hyperglycemia but not hepatic insulin resistance in a transgenic mouse model of type 2 diabetes. Diabetes. 2004;53(11):2901-9.
  59. Farrar JL, Hartle DK, Hargrove JL, et al. A novel nutraceutical property of select sorghum (Sorghum bicolor) brans: inhibition of protein glycation. Phytother Res. 2008;22(8):1052-6.
  60. Park JH, Lee SH, Chung IM, et al. Sorghum extract exerts an anti-diabetic effect by improving insulin sensitivity via PPAR-gamma in mice fed a high-fat diet. Nutr Res Pract. 2012;6(4):322-7.
  61. Poquette NM, Gu X, Lee SO. Grain sorghum muffin reduces glucose and insulin responses in men. Food Funct. 2014;5(5):894-9.
  62. Narotzki B, Reznick AZ, Navot-Mintzer D, et al. Green tea and vitamin E enhance exercise-induced benefits in body composition, glucose homeostasis, and antioxidant status in elderly men and women. J Am Coll Nutr. 2013;32(1):31-40.
  63. Bang H, Kwak JH, Ahn HY, et al. Korean red ginseng improves glucose control in subjects with impaired fasting glucose, impaired glucose tolerance, or newly diagnosed type 2 diabetes mellitus. J Med Food. 2014;17(1):128-34.