Overlooked Dangers of Excess Fasting InsulinMay 2019
By Sonia Whitman
The public is largely aware of the dangers of high blood sugar.
Chronically elevated blood glucose levels damage almost every tissue in the body and accelerate degenerative aging.
A related condition that often goes undiagnosed is elevated fasting insulin.
Long before blood sugar rises, levels of the hormone insulin can be dangerously high.
Elevated fasting insulin is linked to a number of health problems including cancer, Alzheimer’s, high blood pressure, and atherosclerosis.1-8
Not only is fasting insulin seldom checked for, but over-secreting of insulin by the pancreas can artificially lower blood glucose. This can allow a diabetic state to fester for decades before glycemic control is lost, and full-blown type II diabetes develops.
It doesn’t need to be that way.
Fasting insulin can be checked by low-cost blood tests. When elevated, insulin can be reduced through diet, exercise, certain nutrients, and the AMPK-activating drug metformin.
What Is Elevated Fasting Insulin?
Insulin is a hormone made and secreted by the pancreas. It regulates carbohydrate, fat and protein metabolism, and helps cells absorb and process glucose from the bloodstream to keep glucose levels from getting too high.
Eating stimulates the secretion of insulin. Normally, its levels then drop off during the fasting state, when food hasn’t been consumed for some time. This resting level of insulin is called fasting insulin.
But for many people, as they age, and gain weight and fat mass, the body stops responding to insulin as well as it should. This is referred to as insulin resistance. As cells become resistant to the effects of insulin, blood glucose levels rise, along with risk for type II diabetes.
Initially, there can be an extended period when the pancreas makes up for insulin resistance by pumping out high levels of insulin. In this state, called hyperinsulinemia, insulin levels remain high even between meals.
Glucose levels may remain normal, but insulin is still working overtime. This elevated blood insulin level has numerous negative effects on metabolism and leads to changes that can cause disease.1-8
The Dangers of High Fasting Insulin
Research has found that high fasting insulin, or hyperinsulinemia, is linked to a vast range of major health problems, including:
- High blood pressure,7,9,10
- Type II diabetes,13,14
- High triglycerides (which contribute to hardening of the arteries),7,17-19
- Low HDL cholesterol (the “good” cholesterol),7,18,20
- Polycystic ovary syndrome,21
- Benign prostatic hypertrophy (prostate enlargement in men),23
- Migraine headaches,24
- Erectile dysfunction,25
- Skin tags,26
- Inner ear problems, including tinnitus, vertigo, and hearing loss,27
- Alzheimer’s disease,6 and
- Increased risk of heart attack and stroke.28
The list is shockingly long. And the medical literature supporting the connection between high fasting insulin and these conditions continues to grow.
As a whole, the research shows that unchecked high fasting insulin increases the risk for rapid aging of all tissues and numerous degenerative diseases that result.
Testing for Fasting Insulin Levels
Clearly, elevated fasting insulin is a serious problem. But few people know they have it.
It is not routine medical practice to screen for fasting insulin levels. As a result, insulin resistance and hyperinsulinemia usually go unnoticed until blood sugar rises or overt symptoms begin to show.
By that point, high fasting insulin may have done damage that can lead to disease and loss of function over time.
The solution is simple: Get tested. Even people with normal glucose levels should talk to their doctors about having fasting insulin tested regularly.
A fasting insulin test is a helpful tool in the diagnosis of insulin resistance and type II diabetes and may save your life.
The hormone insulin is secreted primarily in response to the intake of carbohydrates. It helps the transport of glucose from the bloodstream into the cells.
Life Extension® believes an ideal fasting insulin level to be <5 µIU/mL.
Additional blood tests to screen for persistently high blood sugar include hemoglobin A1c, fasting glucose, and the glucose tolerance test.
The Link Between Fasting Insulin and AMPK
Treating—or, even better, preventing—high fasting insulin levels is vital.
Unfortunately, most medical treatments address the different symptoms and effects of hyperinsulinemia, not the root problem itself.
For example, doctors generally recommend anti-hypertensive medications to lower blood pressure, and statins to improve cholesterol. These medications help by treating the symptoms, but they don’t address the high fasting insulin levels that caused the underlying problems in the first place.
A better approach would be to correct insulin resistance to keep fasting insulin in the normal range. Only then can a person prevent or correct the harmful effects of excess insulin.
Fortunately, there’s an enzyme found in every cell in the body, called AMP-activated protein kinase (AMPK), that can help get insulin levels back to normal.
When activated, AMPK improves metabolism, boosting cells’ sensitivity to insulin and counteracting many of the detrimental effects discussed above, including weight gain and many age-related diseases.8,29,30
AMPK activation has several specific effects on metabolism, including:8
- Improved glucose transport into cells,
- Improved function of the mitochondria, the “power generators” of the cell,
- Enhanced breakdown of fats,
- Reduction of oxidative stress,
- Reduced inflammation, and
- Activation of sirtuins, proteins that regulate cellular health and are associated with life-span extension in many models.
The end result of these effects? Reduced insulin resistance and lower levels of fasting insulin.
The objective is to find ways to “amp up” AMPK’s activity. The four known ways to do this are with exercise, dietary changes, medication, and natural supplements.
Activating AMPK with Exercise and Diet
We all know that getting regular physical exercise has many health benefits, like burning calories and toning muscles.
But one benefit is often overlooked: Exercise directly stimulates cells to increase AMPK activity.31,32 This is why exercise is associated with weight loss and metabolic benefits beyond what can be accounted for simply by the number of calories burned.
The converse is also true. A sedentary lifestyle leads to lower AMPK activity,8 and is well recognized as a risk factor for obesity, type II diabetes and metabolic syndrome.
The modern Western diet is also partly to blame for many of the metabolic diseases from which people suffer, including hyperinsulinemia. Diets that are high in calories, carbohydrates, and fats put a strain on the system and force insulin levels up, leading to insulin resistance and high fasting insulin levels.
Eating healthier foods and fewer total calories can go a long way towards improving metabolism and boosting AMPK activity. In fact, calorie restriction, either by total reduction in the number of calories consumed or by intermittent fasting, has been shown in research studies to be an activator of AMPK.31,33
For most people, though, making dramatic and consistent changes to diet and exercise is difficult. There are other options that can also be powerful AMPK activators.
Medication and AMPK
Metformin is a drug that, for years, has been used to control elevated blood glucose in patients with type II diabetes.
It works, in part, because it is a potent activator of AMPK, helping to correct underlying metabolic problems and reduce insulin resistance.34-36
For this reason, the medical applications of metformin have been expanding. It is now being used to treat more than just diabetes and is being hailed as a means to slow the aging process and reduce weight gain.34,36,37
Though it is derived from a compound found in the French lilac plant, it is a synthetic medication and requires a physician’s prescription.
LifeExtension® has recommended metformin as an anti-aging drug since 1995 , and the scientific literature continues to support its many benefits. Some people, however, experience gastro-intestinal side effects and cannot take metformin. Others encounter problems persuading their doctor to prescribe metformin for its diabetes-prevention properties.
Using Plant Compounds to Boost AMPK
Fortunately, other plants contain natural compounds with similar AMPK-activating properties.
Gynostemma pentaphyllum is a plant native to parts of Asia. It is known as the “immortality herb” by some local cultures.
Several animal and cell culture studies have shown that G. pentaphyllum and its extracts are activators of AMPK and have related health benefits.38-42
For example, a study utilizing a mouse model of obesity found that by activating AMPK, G. pentaphyllum decreased body weight and cholesterol levels.39
More impressively, human studies have demonstrated metabolic and body fat improvements with G. pentaphyllum comparable to those seen with metformin.
A study published in the medical journal Obesity randomized 80 overweight or obese subjects to receive either 450 mg per day of a G. pentaphyllum extract or a placebo.41
Over a 12-week period, several markers of body fat were reduced in those subjects receiving G. pentaphyllum. Total abdominal fat area, body weight, body fat mass, percent body fat, and body mass index were all reduced in the G. pentaphyllum group, compared to the placebo.
Although all excess body fat can have negative effects, abdominal fat has the strongest impact, significantly contributing to metabolic disease and all its harmful effects.43 Total abdominal fat was reduced by 6.3% over the 12-week period of this study.41
A compound found in citrus fruits called hesperidin has also been found to increase AMPK activity.44-46
A study of mice fed a high fat diet demonstrated that hesperidin supplementation significantly reduced body weight, body fat deposition, blood glucose, lipid levels, and insulin levels. It also reduced a measure of the degree of insulin resistance (the HOMA-IR index).45
In human studies, as well, hesperidin has demonstrated the benefits that come with AMPK stimulation.44,46 In one study, published in the Journal of Clinical Endocrinology & Metabolism, patients with metabolic syndrome, randomized to receive 500 mg of hesperidin per day, benefited from both improved blood vessel function and a reduction in circulating markers of systemic inflammation.46
By activating AMPK, both G. pentaphyllum and hesperidin can help bring high fasting insulin levels back under control.
The dangers of high blood glucose levels associated with metabolic syndrome and diabetes are well known.
But there is another related, yet often undiagnosed threat.
Insulin resistance and high levels of fasting insulin—even in the absence of high glucose—can wreak havoc on our metabolism and lead to numerous long-term effects, ranging from high blood pressure to cancer.
This condition is often missed during routine blood testing that typically measures only markers of elevated glucose, not insulin. Low-cost fasting insulin blood testing can remedy this.
If it’s discovered, elevated fasting insulin can be corrected. Boosting the activity of the enzyme AMPK can help resolve metabolic abnormalities, improving insulin sensitivity and preventing the negative effects of high fasting insulin.
Exercise and dietary changes both help activate AMPK.
Medications such as metformin, and natural plant products, including G. pentaphyllum and hesperidin, have also been shown to have potent AMPK-activating effects.
Together, these interventions can help get high fasting insulin levels under control and prevent the downward spiral into chronic diseases, with which they are associated.
Fasting insulin has been added to the popular Male and Female Blood Test Panels that many readers of this magazine have done annually. Until June 3, 2019, the cost of these comprehensive test panels is reduced to only $199.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Crofts C, Schofield G, Zinn C, et al. Identifying hyperinsulinaemia in the absence of impaired glucose tolerance: An examination of the Kraft database. Diabetes Res Clin Pract. 2016 Aug;118:50-7.
- Erion KA, Corkey BE. Hyperinsulinemia: a Cause of Obesity? Curr Obes Rep. 2017 Jun;6(2):178-86.
- Reaven G. Syndrome X. Curr Treat Options Cardiovasc Med. 2001 Aug;3(4):323-32. (References continue on page 64.)
- Sarafidis PA, Nilsson PM. The metabolic syndrome: a glance at its history. J Hypertens. 2006 Apr;24(4):621-6.
- Tsujimoto T, Kajio H, Sugiyama T. Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: A population-based observational study. Int J Cancer. 2017 Jul 1;141(1):102-11.
- Neumann KF, Rojo L, Navarrete LP, et al. Insulin resistance and Alzheimer’s disease: molecular links & clinical implications. Curr Alzheimer Res. 2008 Oct;5(5):438-47.
- Salonen JT, Lakka TA, Lakka HM, et al. Hyperinsulinemia is associated with the incidence of hypertension and dyslipidemia in middle-aged men. Diabetes. 1998 Feb;47(2):270-5.
- Ruderman NB, Carling D, Prentki M, et al. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest. 2013 Jul;123(7):2764-72.
- Ferrannini E, Haffner SM, Stern MP. Essential hypertension: an insulin-resistant state. J Cardiovasc Pharmacol. 1990;15 Suppl 5:S18-25.
- Modan M, Halkin H, Almog S, et al. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. J Clin Invest. 1985 Mar;75(3):809-17.
- Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000 Aug;106(4):473-81.
- Bonner G. Hyperinsulinemia, insulin resistance, and hypertension. J Cardiovasc Pharmacol. 1994;24 Suppl 2:S39-49.
- Goldstein BJ. Insulin resistance as the core defect in type 2 diabetes mellitus. Am J Cardiol. 2002 Sep 5;90(5A):3G-10G.
- Haffner SM, Stern MP, Mitchell BD, et al. Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity, and body-fat distribution. Diabetes. 1990 Mar;39(3):283-8.
- Burnol AF, Morzyglod L, Popineau L. [Cross-talk between insulin signaling and cell proliferation pathways]. Ann Endocrinol (Paris). 2013 May;74(2):74-8.
- Nilsen TI, Vatten LJ. Prospective study of colorectal cancer risk and physical activity, diabetes, blood glucose and BMI: exploring the hyperinsulinaemia hypothesis. Br J Cancer. 2001 Feb 2;84(3):417-22.
- Godsland IF, Crook D, Walton C, et al. Influence of insulin resistance, secretion, and clearance on serum cholesterol, triglycerides, lipoprotein cholesterol, and blood pressure in healthy men. Arterioscler Thromb. 1992 Sep;12(9):1030-5.
- Ko GT, Cockram CS, Woo J, et al. Obesity, insulin resistance and isolated low high-density-lipoprotein cholesterol in Chinese subjects. Diabet Med. 2001 Aug;18(8):663-6.
- Mykkanen L, Kuusisto J, Haffner SM, et al. Hyperinsulinemia predicts multiple atherogenic changes in lipoproteins in elderly subjects. Arterioscler Thromb. 1994 Apr;14(4):518-26.
- Karhapaa P, Malkki M, Laakso M. Isolated low HDL cholesterol. An insulin-resistant state. Diabetes. 1994 Mar;43(3):411-7.
- Diamanti-Kandarakis E. Insulin resistance in PCOS. Endocrine. 2006 Aug;30(1):13-7.
- Choi HK, Ford ES, Li C, et al. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2007 Feb 15;57(1):109-15.
- Vikram A, Jena G, Ramarao P. Insulin-resistance and benign prostatic hyperplasia: the connection. Eur J Pharmacol. 2010 Sep 1;641(2-3):75-81.
- Fava A, Pirritano D, Consoli D, et al. Chronic migraine in women is associated with insulin resistance: a cross-sectional study. Eur J Neurol. 2014 Feb;21(2):267-72.
- Yao F, Liu L, Zhang Y, et al. Erectile dysfunction may be the first clinical sign of insulin resistance and endothelial dysfunction in young men. Clin Res Cardiol. 2013 Sep;102(9):645-51.
- Sari R, Akman A, Alpsoy E, et al. The metabolic profile in patients with skin tags. Clin Exp Med. 2010 Sep;10(3):193-7.
Kraft JR. Hyperinsulinemia: A Merging History with Idiopathic Tinnitus,
Vertigo, and Hearing Loss. Int Tinnitus J. 1998;4(2):
- Pyorala M, Miettinen H, Laakso M, et al. Hyperinsulinemia and the risk of stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study. Stroke. 1998 Sep;29(9):1860-6.
- Salminen A, Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev. 2012 Apr;11(2):230-41.
- Towler MC, Hardie DG. AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007 Feb 16;100(3):328-41.
- Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016 Jul 15;48(7):e245.
- Kjobsted R, Munk-Hansen N, Birk JB, et al. Enhanced Muscle Insulin Sensitivity After Contraction/Exercise Is Mediated by AMPK. Diabetes. 2017 Mar;66(3):598-612.
- Canto C, Auwerx J. Calorie restriction: is AMPK a key sensor and effector? Physiology (Bethesda). 2011 Aug;26(4):214-24.
- Diabetes Prevention Program Research G. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. 2012 Apr;35(4):731-7.
- Hawley SA, Gadalla AE, Olsen GS, et al. The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes. 2002 Aug;51(8):2420-5.
- Yanovski JA, Krakoff J, Salaita CG, et al. Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. Diabetes. 2011 Feb;60(2):477-85.
- Wang YW, He SJ, Feng X, et al. Metformin: a review of its potential indications. Drug Des Devel Ther. 2017;11:2421-9.
- Dong C, Xie Z, Yu Y, et al. Discovery, synthesis, and structure-activity relationships of 20S-dammar-24-en-2alpha,3beta,12beta,20-tetrol (GP) derivatives as a new class of AMPKalpha2beta1gamma1 activators. Bioorg Med Chem. 2016 Jun 15;24(12):2688-96.
- Gauhar R, Hwang SL, Jeong SS, et al. Heat-processed Gynostemma pentaphyllum extract improves obesity in ob/ob mice by activating AMP-activated protein kinase. Biotechnol Lett. 2012 Sep;34(9):1607-16.
- Nguyen PH, Gauhar R, Hwang SL, et al. New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum. Bioorg Med Chem. 2011 Nov 1;19(21):6254-60.
- Park SH, Huh TL, Kim SY, et al. Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): a randomized, double-blind, placebo-controlled trial. Obesity (Silver Spring). 2014 Jan;22(1):63-71.
Wang J, Ha TKQ, Shi YP, et al. Hypoglycemic triterpenes from Gynostemma
pentaphyllum. Phytochemistry. 2018 Nov;155:
- Matsuzawa Y, Shimomura I, Nakamura T, et al. Pathophysiology and pathogenesis of visceral fat obesity. Obes Res. 1995 Sep;3 Suppl 2:187s-94s.
- Ohara T, Muroyama K, Yamamoto Y, et al. Oral intake of a combination of glucosyl hesperidin and caffeine elicits an anti-obesity effect in healthy, moderately obese subjects: a randomized double-blind placebo-controlled trial. Nutr J. 2016 Jan 19;15:6.
- Pu P. [Protection mechanisms of hesperidin on mouse with insulin resistance]. Zhongguo Zhong Yao Za Zhi. 2016 Sep;41(17):3290-5.
- Rizza S, Muniyappa R, Iantorno M, et al. Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome. J Clin Endocrinol Metab. 2011 May;96(5):E782-92.