The Insulin/Cancer ConnectionJune 2016
By Miles Mueller
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
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
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
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.
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- 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.
- 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.
- 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.
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- 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.
- 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.
- Available at: http://www.cancer.org/cancer/colonandrectumcancer/detailedguide/colorectal-cancer-key-statistics. Accessed February 29, 2016.
- 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.
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- 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.
- 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.
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