Wednesday, July 7, 2010

Control Insulin, Control Cancer and Chronic Diseases

Benefits/Risks of Insulin

Controlling insulin reaps many rewards. As the previous article suggests, insulin is an ancient hormone ubiquitous in all animals -- from worms to humans -- with classic/nonclassic responsibilities including (see Table 1). Some of these actions are beneficial like thermogenesis, however many of the others are detrimental in the great majority of situations:
--low potassium
--raised heart rate
--increased uric acid (ie, gout
--increased clotting
--CNS stimulation (ie, anxiety, epression, ADHD)
--prevention of fat from being liberalized for energetic uses

We require only tiny, neglible amounts of insulin for thermogenesis and shuttling of energy (glucose) into muscles and liver for storage.

Damage from Insulin Resistance

In fact, increased energy expenditure is exponentially increased when insulin resistance is kept at bay. What is insulin resistance (IR)? It is like being at a rock concert (or Hannah Montana venue with screaming little girls everywhere) where temporary hearing loss is induced by inclement noise pollution. As soon as the volume returns to a low level, hearing resumes. Shut insulin down by going grain-free, carb-restricted, intermittent fasting and exercising, then inflammatory responses and processes are cut off. The same research demonstrated that men and women have blunted energy expenditure when the 'volume of insulin' is dialed exceptionally high. And for us women, we may even have a 'negative' energy output (in other words 'storage') with energy expenditure during the presence of insulin resistance... Insulin-resistant gals may gain weight with exercise lower rates of energy expenditure... This actually is a common phenomenon and very discouraging for women trying to lose weight and fight an uphill battle as they eat per conventional medical advice 'low fat'/high-carbohydrate/insulin-inducing diets (USDA 'whole grain' pyramidal nonsense).

How To Reduce Insulin Resistance

Degrees of IR can also be effectively cranked down by (Isharwal S, et al. Dietary nutrients and insulin resistance in urban Asian Indian adolescents and young adults.Ann Nutr Metab. 2008;52(2):145-51.):
--normal BMI achievement
--reduction of pro-inflammatory omega-6 oils (nuts, beans, oils from corn soy peanut sunflower)
--increase of anti-inflammatory omega-3 EPA+DHA oils (ie, cod liver, fish oil, pasture-fed milk, meat, eggs, etc)

And of course...wheat avoidance, grain elimination, carb restriction, intermittent fasting and exercise.

Excessive insulin (ie, hyperinsulinemia) leads to the below changes (see below diagram):
--generation of TGs and small dense atherogenic LDL
--conversion from fatty streaks to plaque
--plaque growth
--increased adipose tissue mass (Obesity, Metablic Syndrome, PCOS)
--accumulation of Triglycerides in non-adipocytes
--nonalcoholic steatohepatitis (fatty liver/NAFLD)
--pancreatic beta-cell failure (fatty pancreas, insulin resistance)
--dilated cardiomyopathy (myocyte (heart cell) stiffening and diastolic dysfunction)
--arterial stiffening
--blood glucose spikes
--expansion of visceral fat (belly fat colonies)
--fatty liver, fatty pancreas, fatty gallbladder, fatty heart (lipotoxicity)
--Diabetes Type 2
--strokes, heart attacks
--cancer (see end)

Lipotoxicity from Excessive Grains and Carbohydrates

Whole human systemic organ functions may become dominated by hyperinsulinemia, leading to all sorts of dysfunction and energy dysregulation. Why rely on primitive petrol... when nuclear power exists? Mitochondria are the powerhouses of ATP, nuclear energy. Excessive carbohydrates shut mitochondria off... and lead to lipotoxicity.

Fig 1. Lipotoxicity in humans originates from excessive release of free fatty acids from hypertrophied adipocytes in obese persons. Organ exposure to high levels of free fatty acids causes lipid droplets to accumulate within the cytosol of nonadipose tissues in proximity to mitochondria (white arrows, bottom).By-products of cytosolic triglyceride accumulation and of lipid metabolism may lead to organ dysfunction and failure. McGavock JM, Victor RG, Unger RH, Szczepaniak LS. Adiposity of the heart, revisited. (Full PDF here.) Ann Intern Med. 2006 Apr 4;144(7):517-24. Review. PMID: 16585666

The inflammation associated with insulin is akin to the oxidative damage that occurs when soft materials like rubber or plastic is left outside exposed to the elements. Over time, the rubber hardens and becomes inelastic and rigid, easily breaking with any shear force. Sort of like running a high-powered hose made out of glass, right? With the elimination of inflammatory influences, human tissues can return to their original soft, elastic, pliable states. This includes endothelium, heart blood vessels, contractile tissues like our heart and skeletal muscles... even our oral gum tissues.

Reversal occurs when insulin is shut down.

The previous review of the research eloquently illustrates the special properties that dictate this ancient 'reactive' hormone. Insulin is one of the few hormones that is controlled by consumed 'substrates'.... What is in charge of turning insulin on and off? What are substrates of insulin?


Food composition directly lowers or raises insulin concentrations. Various other factors of course determine how quick and how sustained hyperinsulinemia occurs (exercise, weight loss, skeletal muscle dominance, size and location of visceral fat colonies (ie, 'belly' is 'bad') but in essence our food controls blood insulin levels.

If what we put in our mouth dictates are insulin levels, then equally powerful is what we don't... In other words, processes like starvation, skipping meals, random eating, intermittent fasting and going low-carb or restricted-carb are ways to reduce and control insulin. Consumption of adequate protein and fats and fiber control insulin release as well.

Consider the complete avoidance of all wheat and grains:
--wheat products (incl cereal, pasta, noodles, bread, crackers, pita, tortilla)
--bulgur (cracked wheat)
--oat (except oat bran)
--corn (incl popcorn, grits, cornmeal, tortilla, chips)
--et cetera

Consume most of the carbohydrates from non-starchy vegetables and raw nuts/seeds and low-GI fruit like berries.

Cancer and the Carbohydrate and Insulin Connection

Controlling insulin not only controls CAD but also controls cancer... Is 'whole grains' just promoting 'whole C-A-N-C-E-R'? As well as 'whole CORONARY ARTERY DISEASE'?
--breast cancer
--prostate cancer
--colon cancer
--pancreatic cancer
--brain cancer
--gallbladder cancer
--kidney cancer
--thyroid cancer

Cancer and Carbs/Insulin References
  • Berstein LM. Endocrinology of the wild and mutant BRCA1 gene and types of hormonal carcinogenesis. Future Oncol. 2008 Feb;4(1):23-39. Review. PMID: 18240998
  • Hede K.Doctors seek to prevent breast cancer recurrence by lowering insulin levels.
    J Natl Cancer Inst. 2008 Apr 16;100(8):530-2. PMID: 18398091
  • Barnard RJ.Prostate cancer prevention by nutritional means to alleviate metabolic syndrome. Am J Clin Nutr. 2007 Sep;86(3):s889-93. Review.PMID: 18265484
  • Park JH.Inhibition of colon cancer cell growth by dietary components: role of the insulin-like growth factor (IGF) system. Asia Pac J Clin Nutr. 2008;17 Suppl 1:257-60. PMID: 18296350>
  • Tenenbaum A, et
    al. Does the lipid-lowering peroxisome proliferator-activated receptors ligand bezafibrate prevent colon cancer in patients with coronary artery disease? Cardiovasc Diabetol. 2008 Jun 19;7(1):18. PMID: 18565233

  • Pisani P. Arch Physiol Biochem. 2008 Feb;114(1):63-70. Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies.

    Background: A substantial body of evidence links sex hormones, diet, excess body weight and physical activity to the risk of developing cancer at several sites common in affluent countries. The hypothesis that high circulating levels of insulin could be the underlying factor increasing cancer risk has been proposed. Epidemiological studies on markers of hyper-insulinaemia and cancer are reviewed and summarized.
    Methods: Studies of cancers of the colon and rectum, pancreas, breast, and endometrium examining the association with blood levels of C-peptide, insulin, glucose, glycated haemoblobin (HbA1c) were searched in PubMed. Multivariate, adjusted relative risks (RR) and their 95% confidence intervals were abstracted and summarized by meta-analyses.
    Results: Most of the studies identified were cohorts that relied on measurements obtained at baseline or assessed in blood stored at low temperature several years before the onset of cancer. The meta-analyses showed excess risks of colorectal and pancreatic cancers associated with higher levels of circulating C-peptide/insulin and with markers of glycaemia. Significant heterogeneity was found among four epidemiological studies of endometrial cancer and C-peptide giving a summary RR compatible with no association. Overall breast cancer risk was significantly higher in the upper categories of C-peptide/insulin, however, the excess derived entirely from retrospective studies.

    Conclusion: Current evidence suggests that subjects who develop colorectal and pancreatic cancers have increased pre-diagnostic blood levels of insulin and glucose. PMID: 18465360

This is post is a reprise from two years ago... sadly holds true more than ever.

Evolutionary Medicine post:
Metformin, Insulin Resistance and Cancer


Dr. T said...

Wow. That is an EM post at its best!! Love it.

Danny Roddy said...

Great post G!

Morhangeois said...

A timely reminder for me. Sometimes we need a direct reminder of why we are making these changes to our diet. Thank you very much.

Dr. B G said...

Hey Rockstar,

Like ur latest ebook and tunes!!


Dr. B G said...


Always welcome :)


Dr. B G said...


This post initially was inspired 2yrs ago from a friend L, his son was roommates at one time with Robb W. L packs heat (former detective), runs a HIIT gym, gets paid to design and engineer racing paddleboards :) In his spare time he studies biochem *haa* Plus he has reversed his CAC ebct progressions...!



When I grow up I wanna be like him... oh yeah he is professor too.

Fitnatic said...

Ah, giving up even quinoa is so hard. Ironically the study you cited about Indians ( please only India has Indians)- a grain free diet will NEVER work there or generally in south Asia. It might take generations for that to happen.
Also, prior generations were doing quite well on a grain based diet. So I think that taking out just the modern franken elements like industrial oil and sugar will make a huge difference.

Anonymous said...

This is where I come from!

Our family (well one side of it) has a weird syndrome where we have some but not often all indicators of Metabolic Syndrome (insulin resistance) and Type 2 diabetes but unrelated to overweight. Also there is zero cancer. Everyone dies of CVD though often at an advanced age. They should study our genes to see what it is we're doing right

By doing this

I reduced my IR. Assuming trigs/HDL is related to IR I went from over 15 to less than unity by eating pretty much the exact opposite of what the dietician told me.

I can generate short term IR by eating excessive carbs. How do I know? My BG meter tells me I have excess glucose but my muscles refuse to find it. The concept of finding when my BG peaks after eating and reducing the spike was #1 factor in controlling this and has led me to eating far less carbs, eliminating wheat and sugar and also reducing Omega 6s and replacing them with sat fats, monounsaturates and Omega 3s. Grass-fed meat, fish, coloured veggies yum yum!

I'm still fine tuning the results but I'm certain my insulin level has dropped precipitously which is what has got my lipids and BP in line.

I wish I could get this through to some of my relatives who are still fixated on low fat high carb vegetarianism.

Personally I don't do well with fasts. Many diabetics get "Dawn Phenomenon" where BG increases relentlessly until something is eaten. I don't do that but my liver will panic and dump an excess of glucose if I exercise in a fasted state. Alpha lipoic acid helps with that, but my strategy is to eat a high protein moderate fat low carb breakfast and add more fat later in the day, which keeps my BG within normal limits and presumably does the same for my insulin levels.

I don't need to snack nearly as often as I did and don't run out of energy whatever I'm doing. Bypassing glucose and insulin and utilising fats and ketones as fuel seems to be the key.

Whether I die of CVD or cancer I'll let you know posthumously

ProudDaddy said...

How does one separate the effects of hyperinsulinemia from hyperglycemia? That is, is it the insulin or the glucose? If insulin is the toxin, then whey protein has to be extremely toxic, and bodybuilders should soon be dropping like flies!

Dr. B G said...


Thanks for your question -- people have been debating this in the paleoblogosphere and I think it is a bit loaded, but not really.

Insulin is a spectrum and unfortunately I've been on both ends now (obese <---> ketotic/intermittent fasting).

So like Type2 diabetes on one side, and Type1 on the other, they are contrasting dichotomies and absolutely different physiologies and phenotypes. Type 2 is excessive glucose and insulin and very high insulin resistance. Type 1 is excessive glucose but nada insulin (auto-immune destruction of the pancreatic beta islet cells which produce insulin).

We need some insulin -- a spike after meals to shuttle protein and carbs into cells for use and storage. Too much from refined carb and high carb diets leades to hyperinsulinemia chronically which leads to disease.

Bodybuilders, athletes, people who move around, and sumo wrestlers are unique in thatthey maintain high insulin sensitivity in their muscles. Type 2 diabetics generally do not. Often this is enough to prevent both hyperglycemia and hyperinsulinemia... Body builders do know this and 'abuse' pharmaceutical insulin to grow muscles.

Muscle IR (insulin resistance) is probably the key to chronic disease, aging and systemic inflammation. Exercise (chronic, routine) is the about the only way I am aware of that ameliorates muscle IR (and PPAR-delta + ampk agonists, hint). Fish oil does help, but only combined with routine exercise... Cortisol and adrenaline (and hormone deficiencies -- thyroid, progesterone, testosterone) are the best ways to jack up muscle IR.