Hyperinsulinemia and cancer – Cancer 2

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There is a strong relationship between cancer and obesity as discussed in our last post. Since I’ve spent several years arguing why hyperinsulinemia is the root cause of obesity and type 2 diabetes, it would only make sense that perhaps i think it may play a role in cancer development, too.

This link has been known for quite some time, although it has been obscured in the hurry to proclaim cancer a genetic disease of accumulated mutations. Since obesity and hyperinsulinemia is clearly not mutagenic, this relationship is easily forgotten, but emerges once again as the paradigm of cancer as a metabolic disease begins to be considered seriously. For example, it is quite simple to grow breast cancer cells in a lab. The recipe has been used successfully for decades. Take breast cancer cells, add glucose, growth factor (EGF) and insulin. Lots and lots of insulin. The cells will grow like weeds after a spring shower.

But what happens when you try to ‘wean’ them off insulin? They drop off and die. Dr. Vuk Stambolic, a senior cancer researcher says it’s like “They’re addicted to (insulin)”.

But wait a second, here. Normal breast tissue is not particularly insulin dependent. You find insulin receptors most prominently in liver and skeletal muscle cells, but breast? Not so much. Normal breast tissue doesn’t really need insulin, but breast cancer cells cannot live without it.

In 1990, researchers found that breast cancer cells contain over 6 times the number of normal insulin receptors as normal breast tissue. That would certainly explain why they need insulin so bad. Indeed, it is not simply breast cancer that shows this, but hyperinsulinemia is also linked to colon cancer, pancreas, and endometrium.

Many tissues that are not particularly rich in insulin receptors develop cancers that were chock full of them. There must be a reason, and that reason is fairly obvious. The growing cancer requires glucose to grow – both for energy and as raw material to build with – and insulin could help bring in a flood of it.

But there was another concern about the high insulin levels – the development of insulin like growth factor 1 (IGF1). Insulin promotes the the synthesis and biologic activity of IGF1. This peptide hormone has a molecular structure very similar to insulin and it regulates cellular proliferation. This was discovered in the 1950s although the structural similarity to insulin was not noted until 2 decades later. Because of those similarities, insulin easily stimulates IGF1 as well.

This certainly makes sense to link a nutrient sensing pathway like insulin to growth of cells. That is, when you eat, insulin goes up since most meals, except maybe pure fat, causes insulin goes up. This signals the body that there is food available and that we should start cellular growth pathways. After all, it makes no sense to start growing cells when there is no food available – all those new baby cells would just die. *sniff…*

This is also born out in classic animal studies of the effect of starvation on tumours. First noted in the 1940s by Peyton Rous and Albert Tannenbaum, rats with a tumor induced by virus could be kept alive by only giving barely enough food to keep them alive. Once again, this kind of makes sense. If the rat’s nutrient sensors figured there wasn’t enough nutrients, all growth pathways, including those of cancer cells would be inhibited.

In vitro studies have clearly shown that both insulin and IGF1 act as growth factors to promote cell proliferation and inhibit apoptosis (programmed cell death). Animal studies that inactivate the IGF1 receptor show reduced tumor growth. But another hormone also stimulates IGF1 – growth hormone. So, growth hormone (GH) is bad, too?

Well, it doesn’t quite work like that. There’s a balance. If you have too much growth hormone (a disease called acromegaly) you find excess levels of IGF1. But in the normal situation, both insulin and GH stimulate IGF1. But insulin and growth hormone are opposite hormones. Remember that growth hormone is one of the counter-regulatory hormones, meaning it does the opposite of insulin.

As insulin goes up, GH goes down. Nothing turns off secretion of GH like eating. Insulin works to move glucose from the blood into the cells, and GH works in the opposite direction – moving glucose out of (liver) cells into the blood for energy. So, there is no real paradox here. Normally, GH and insulin move in opposite directions, so IGF1 levels are relatively stable despite fluctuations in insulin and GH.

Under conditions of excess insulin (hyperinsulinemia) you get excessive IGF1 levels and very low GH. If you have pathologic GH secretion (acromegaly) you will get the same situation. Since this occurs only in those rare pituitary tumours, we will ignore this, since its prevalence pales in comparison to the epidemic of hyperinsulinemia in current Western civilization.

The liver is the source of over 80% of circulating IGF1, of which the main stimulus is GH. However, in patients who are chronically fasting or type 1 diabetes, low insulin levels cause reductions in liver GH receptors and reduced synthesis and blood levels of IGF1.

In the 1980s, it was discovered that tumours contain 2-3 times more IGF1 receptors compared to normal tissues. But yet more links were discovered between insulin and cancer. PI3 kinase (PI3K) is another player in this network of metabolism, growth and insulin signalling, also discovered in the 1980s by Cantley and colleagues. In the 1990s it was discovered that PI3K plays a huge role in cancer, too with it’s links to the tumor suppressor gene called PTEN. In 2012, researchers reported in the New England Journal of Medicine that mutations in PTEN increased the risk of cancer, but also decreased the risk of type 2 diabetes. Because these mutations increased the effect of insulin, blood glucose went down. As blood glucose went down, diagnosis of type 2 diabetes went down as this is how it is defined. PTEN mutations are one of the most common ones found in cancer

However, the diseases of hyperinsulinemia, such as obesity went up. The important point was that cancer, too is a disease of hyperinsulinemia. This is not the only time this has been found. Another study from 2007 used genome wide association scanning to find genetic mutations linked to prostate cancer. One of these mutations found increased risk of cancer, while decreasing risk of type 2 diabetes.

Further, many of the genes that increase the risk of type 2 diabetes are located in very close proximity to those genes that are involved in cell-cycle regulation, or the decision whether this cell proliferates or not. At first glance, this may not make sense, but closer examination reveals the obvious connection. The body makes a decision whether to grow or not. During times of famine or starvation, it is not advantageous to grow, because this would mean there are ‘too many mouths to feed’. So, the logical thing to do is to increase apoptosis (programmed cell death) to cull some of these extraneous cells.

Autophagy is a related process to rid the body of unneeded sub cellular organisms. These extra mouths – like a free loading uncle who has overstayed his welcome – are shown the door because resources are scarce. Nutrient sensors, like insulin and mTOR (which we’ll talk about later) are therefore critical to making the decision of whether cells should grow or not.

It’s known that insulin and IGF1 play a crucial role in apoptosis. Indeed, there is a threshold for IGF1. Below that level, cells will enter apoptosis, so IGF1 is a survival factor for cells.

There are two major factors in cancer. First – what makes a cell become cancer. Second – what makes a cancerous cell grow. These are two entirely separate questions. In addressing the first question, insulin does not play a role (as far as I can tell). However, certain factors increase the growth of cancerous cells. Cancer is derived from normal tissues, and growth factors for those cells will increase the growth of cancer.

For example, breast tissue is sensitive to estrogen (it makes it grow). Since breast cancer is derived from normal breast tissue, estrogen will make breast cancer cells grow too. Hence, anti-estrogen treatments are effective in helping breast cancer not recur (eg. Tamoxifen, aromatase inhibitors). Prostate cells need testosterone and hence blocking testosterone (eg. via castration) will help treat prostate cancer, as well. Knowing what makes tissues grow is valuable information that leads to viable cancer therapy.

Now, what if there are general growth factors that are effective in virtually all cells? This would not make a difference in answering why cancer develops, but would still be valuable in adjunctive treatment of cancer. We already know there are these growth signal that exist in almost all cells. These pathways have been conserved for millennia all the way back to single celled organisms. Insulin (responsive to carbohydrates and protein, especially animal). Yes, but even more ancient and perhaps more powerful, mTOR (responsive to protein).

What if we already knew how to lower these generalized growth signals (nutrient sensors)? This would be an unimaginable powerful weapon to prevent and help in treatment of cancer. Lucky for us, these methods already exist, and they’re free. What is this? (If you don’t know already, you must be a new reader)

Fasting. Boom.

2017-10-12T17:23:46+00:00 34 Comments

About the Author:

Dr. Fung is a Toronto based kidney specialist, having graduated from the University of Toronto and finishing his medical specialty at the University of California, Los Angeles in 2001. He is the author of the bestsellers ‘The Obesity Code’ and ‘The Complete Guide to Fasting’. He has pioneered the use of therapeutic fasting for weight loss and type 2 diabetes reversal in his IDM clinic.

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34 Comments on "Hyperinsulinemia and cancer – Cancer 2"

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William E. Rocque
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Could cholesterol resistance be caused by statins? You start with 20gms Lipitor and your cholesterol goes down, but then your liver says hey that not enough cholesterol, so it produces more… the doc ups your Lipitor to 40mgs and cholesterol goes down, but liver says hey, that’s not enough and produces more… then 60mgs… then 80… then what… all the while the same thing is happening to your Diabetes… I was born with a hole in my heart and a torn valve… at age 14 the hole was larger than a silver dollar and the tear had increased in length… Read more »
Mike Bravo
Guest
Hb1Ac went from 9.2 to 6.4 over the last three months. Dr. asked what was doing, so I told him about my rounds of fasting and intermittennt fasting. He was really surprised when I said that my problem was likely that i had too much insulin (as opposed to merely too much glucose), and that my plan was to restore my insulin sensitivity because insulin can be toxic in excess amounts. You would have thought I was presenting JAMA research, but he agreed to me backing off the ladt of my meds as long as my blood sugar stayed under… Read more »
Pete
Guest

As an occasional freeloading uncle, thanks for another great post!

Sharon deRham
Guest

I always look forward to Dr. Fung’s posts. I learn so much from them. Thanks a lot.

sten bjorsell
Guest
Brilliant explanation. Many thanks, Jason! It really means that with a bit of thought and discipline anyone of us can reverse cancer at home! Intermittent fasting for one or two days in a row does not need medical supervision. Cutting out most carbs and reducing proteins during refeeding, is the only “treatment” that most of us would like some help with. And that lactic acid is really an antioxidant that is protecting cancer from our immune system by quenching its oxidizing weapons with acidic clouds and helping it to spread to new cells does not even need to come into… Read more »
Roger Bird
Guest

Another out-of-the-park home run by the Toronto Bluejays.

Steve
Guest

My Sis who has never been fat, never smoked, never had a diabetic or insulin problem. She is thin healthy and young was just diagnosed with lung cancer. Go figure

Alerson
Guest

This post and mostly the previous make it pretty clear: of course, CANCER is a MULTIFACTORIAL disease. This fact doesn´t invalidate Fung´s point.

Hope she´ll do fine and hope other weapons will be ready to be used against that lung tumor!

My best,

Elle
Guest

Was she exposed to second hand smoke? Just a thought.

Bob O'Connell
Guest

Oh please Elle. How about 2nd-Hand Industrialized Society.

Steve — best to your sister. (BTW, how would you know your sister did not have hyperinsulinemia unless she had a simultaneous 5-hour GTT and insulin assay?)

Peggy
Guest

Radon gas (in our homes – test basements) is the second leading cause of lung cancer in the U.S.

M Winter
Guest

That we should know all of this, now, in our lifetime is amazing. That the rest of the world will most likely ignore and avoid this knowledge is a travesty.

Wayna
Guest

Thank you Dr Fung for another great article. Though it takes a while for me to understand what you’re describing, I get the the gist. Fasting!

Sarah Gaunt
Guest

“Since breast cancer is derived from normal breast tissue, estrogen will make breast cancer cells grow too. Hence, anti-estrogen treatments are effective in helping breast cancer recur (eg. Tamoxifen, aromatase inhibitors).”

Do you really mean “helping breast cancer RECUR”? Surely that’s a typo and it should be “NOT recur”?

Carolyn
Guest

What about triple negative breast cancer? What makes it grow?

palo
Guest

I’m a four times cancer survivor and may have gotten it again on my lung. Which fasting protocol would be most effective to prevent it and get rid of it?

Kitty
Guest

Read the book AntiCancer by David Servan-Schreiber. Then up your variety of veggie intake to 8-10 per day, plus green tea. Meditate. Exercise. Get good sleep. Create the best environment possible for you immune system to be successful.

Raj Kumar
Guest

Fasting. Boom. Love it! Well done Dr Fung.

Ken Stephens
Guest
Excellent post! Excessive insulin levels does contribute to cancer risk, and all you have to do is understand how insulin works to get this. The scary thing here is when you look at how many people have hyperinsulinemia these days. It’s the majority of the population. Big medicine licks its chops and they certainly don’t want you to know anything about high insulin, especially the fact that it promotes cancer, because that’s such a big cash cow for them. I did an article on the brain’s sensing of lack of glucose driving excess endogenous glucose production and this is a… Read more »
Barbara
Guest
It gets worse and worse. I have a friend who just underwent quadruple bypass surgery. He complained that he had to take lots of pills. When I asked him what he was taking he said “I don’t know, I just take what the doctor told me.” He was so horribly constipated he had to go back into hospital and have an enema – he’s been given iron tablets, but has no idea that iron can cause constipation. When I pointed out that he might ask his doctor about other, gentler ways to 1) get some iron, and 2) avoid constipation… Read more »
Ken Stephens
Guest
I also want to add that the biggest effect of high insulin on cancer is the excessive delivery of glucose into cells. Under the condition of hyperinsulinemia, too much glucose gets put into our cells, this is one of the things insulin does and high insulin does it more. This is how we get fat. Cancer cells love glucose. and we have turned ourselves into an all you can eat buffet for them. Insulin in excessive amounts is also inflammatory, very much so, and this makes things worse. We get cancer cells every day and a healthy subject will just… Read more »
Sean Raymond
Guest
This isn’t correct – insulin merely speeds up the rate of glucose uptake into cells, it is not absolutely essential for it. In hyperglycaemic states, if you stop the insulin response you will still actually see enhanced glucose disposal due to a gradient effect. In many cases, Hyperinsulinaemia indicates impaired glucose metabolism and merely signifies that more insulin is needed for normal glucose clearance. Insulin does not cause people to be fat whilst the idea about glucose feeding cancer cells is interesting, as someone who works in oncology, I see many cancer patients who are literally starving, this does not… Read more »
Jitka Egressy
Guest

Oh, great explanation. Can fasting help with all types of cancer? I read in some papers, that not all types can be “starved” to death. Thanks for your work!!!

sten bjorsell
Guest
Jitka, I think the answer is yes. Definitely a help if not a cure for all cancers! Intermittent Fasting (IF) is definitely a multi sided sword against cancer. 3 or 4 sides: IF slows cancer growth by reducing insulin and IGF-1 with low protein and low carb intake between fasts as Jason Fung just described. (1) IF also clears out old dysfunctional cells via autophagy and replaces them with new cells as required. This resharpens all bodily systems, in particular, the white blood cells – our immune system – as described by Valter Longo.(2) IF reduces the antioxidants that active… Read more »
Hans Dahl
Guest

Mr Fung,

Thank you SO very much for your extremely important discoveries! And please look at what this humble and ernest person have said, relatively long ago:

https://www.amazon.com/Breuss-Cancer-Cure-Rudolf/dp/0920470564/ref=sr_1_1?ie=UTF8&qid=1503594758&sr=8-1&keywords=rudolf+breuss

Tt really corresponds with Yout theories!

Best wishes on Your Efforts!

/Hans Dahl (Sweden)

Bob
Guest

Does fasting decrease oestrogen and testosteron? Does it need to in the cases of prostate and breast cancer? What have I missed?
Stopping cancer developing seems like a big deal, an important question, to me…
Do men with breast cancer have high oestrogen levels?

Bob
Guest

And are all those risk figures relative?

Srinath
Guest

What do you mean by Chronic fasters ? I have fasted for several iterations of 2 to 20 days total with 1 meal separating the fasts. Would that make me a chronic faster ?

Jerome Kahn
Guest
I’ll make it brief, there is another theory of causes of cancer, one that pharma doesn’t like. The two main points are the Warburg hypothesis, in which Otto a Noble Laureate showed in 1924, and wrote on for the next 40 years, has defective mitochondria, and that it can only metabolize glucose anaerobic. That is why cancer has a 6 fold oar greater increase in insulin receptors, so they can hog the glucose. The long lecture by Prof. Thomas Seyfried on YouTube goes over the evidence, also his book Cancer a Metabolic Disease… He treats cancer with a ketogenic diet.… Read more »
Sean Raymond
Guest
An interesting area in need of much more research and evidence. I thank Dr Fung for such articles, my only criticism is the idea that hyperinsulinaemia is the root cause of obesity/diabetes. Insulin does not make a person fat – fatness is determined by the energy status of the cell, and only if that is a state of over abundance would insulin then have a role in the growth of adipose tissue. Our best evidence shows that low CHO diets that lowered insulin levels in eucaloric or hypocaloric diets does not lead to any more fat loss when compared to… Read more »
sten bjorsell
Guest
Sean Raymond, If you take the time to read other posts and/or Dr. Fung’s Book “The obesity code”, you will find the evidence that insulin is fattening. In particular, you will find that insulin dependent diabetics consistently gained more weight when they controlled their blood sugar to “ideal” values with insulin. Otherwise, fasting is the key to lower insulin so that fat from both liver and pancreas can be used for metabolism, followed by better-working organs, including little or no dawn syndrome, once the fatty liver is gone. The low CHO diet, or as it is called, LCHF, emphasizes low… Read more »
Sean Raymond
Guest
Thank you for your reply Sten. I reiterate what I said previously – insulin does not cause fatness. In uncontrolled diabetes that become somewhat controlled when insulin therapy is initiated we see a bringing down of glucose below the renal threshold meaning that that person is peeing out less sugar – i.e. calories. This is one factor in weight changes/adiposity that may be seen. Do you have a link to any studies that prove insulin therapy increases fat deposition The idea that lowering insulin reduces body fat in eucaloric conditions is such a testable idea – and it has been.… Read more »
sten bjorsell
Guest
Sorry, but there are severl trial showin that intensive insulin treatment drives up weight. What you mention about renal theshold is not coming into play at all when “normal diabetics” went to control their diabetes from typically 7 to 5.5 GB. Renat threshold is somewhere over 8. See the weight gain in the Accord study here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714487/ The study, as you may know, was terminated early due to too progressively increased all cause mortality in the intensive arm. If you have studies demonstrating the opposite, please post the link(s)! Jason Fung has covered most of these things in detail in… Read more »
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