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A Discussion About the Paleo Diet's Impact on IGF-1 and Cancer

By Loren Cordain, Ph.D., Professor Emeritus, Founder of The Paleo Diet
March 2, 2012
A Discussion About the Paleo Diet's Impact on  IGF-1 and Cancer image

Dr. Cordain,

Do you have data looking at the changes of IGF-1 and IGFBP-1/ IGFBP-3 prior to and post initiation of the Paleo Diet? Would be interesting to know...


Dr. Cordain:

Dear Shalin,

We havent directly tested this, but my colleague Jennie Brand Miller at the Univ of Sydney has come close with a study (attached) of low glycemic carbs on IGF-1 and IGFBP-3. In this regard, we have compiled data in hunter gatherer and non-westernized populations showing that epithelial cell cancers (breast, colon, prostate were rare or non-existent) and have reason to believe that their diets favorably affected lifelong concentrations of IGF-1 and IGFBP-3 as well as other environmental factors (vitamin D) known to influence oncogenesis.

Best wishes,
Loren Cordain, Ph.D., Professor Emeritus


Professor Cordain,

I hope this email finds you well. Sorry for the delay in getting back to you in greater detail, but I wanted to get your thoughts. Curiously, in the paper you provided, there was no change in systemic IGF-1 between the groups, though the IGF-1/IGFBP-3 ratio were favorably affected by the low GI diet.

A few thoughts

1) I am interested in investing the role of diet and cancer recurrence in the patients I treat to remission. Not everyone has an equal risk of recurrence. IGF-1 has received a LOT of attention recently, with IGF-1 Receptor blockers billed as the next major blockbuster drugs.

2) I am concerned that IGF-1 Receptor blockers will not work as long as IGF-1 is elevated systemically. This is due to a number of different bypass mechanisms that IGF-1 can take to get around the blockade.

3) IGF-1 seems to be most correlated with dietary protein intake, based on a few small animal and human studies in groups with a near fanatical devotion to their respective diets(see below). Not conclusive, but hypothesis generating.....

4) I recently analyzed approximately 115 patients in my dad's weight loss clinic in NY (// IGF-1 levels were measured at baseline and again 2-3 months post intervention. Patients were placed on a calorie restricted diet (800-1000 cals/day), and given prepared meals of 10% fat, 40% Low GI carbs, and 40% protein. All patients pre-study consumed a standard western diet (50% carb, 20-30% protein, 20-30% fat). Doing a paired nonparametric test of means (ie, using patients as their own control), there was a statistically significant reduction in weight, but elevation in systemic IGF-1.

5) This is why I asked if you had measured IGF-1 directly in Paleo Diet patients. My concern is that recommendations of 30% protein or greater may in fact be leading to inadvertent elevations in systemic IGF-1, which could be extremely detrimental for cancer patients.

6) As IGF-1 can be secreted both in the liver as well as tumor, we are going to initiate further study in cancer patients during a typical course of radiation...

Any further thoughts or data regarding IGF-1 and protein intake?

Some references appear below...any thoughts appreciated,


Sanchez-Gomez M, Malmlof K, Mejia W, et al. Insulin-like growth factor-I, but not growth hormone, is dependent on a high protein intake to increase nitrogen balance in the rat. Br J Nutr. 1999 Feb;81(2):145-52.

Gerrits WJ, Decuypere E, Verstegen MW, Karabinas V. Effect of protein and protein-free energy intake on plasma concentrations of insulin-like growth factor I and thyroid hormones in preruminant calves. J Anim Sci. 1998 May;76(5):1356-63.

Murray BM, Campos SP, Schoenl M, MacGillivray MH. Effect of dietary protein intake on renal growth: possible role of insulin-like growth factor-I. J Lab Clin Med. 1993 Dec;122(6):677-85.

Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell. 2008 Oct;7(5):681-7.

Dr. Cordain:

Dear Shalin,

Many thanks for sharing this information with me. I do not claim to be an expert in this area, but I will pass your information on to colleagues who may provide you with their thoughts. Our working hypothesis is that high protein diets similar to those of our ancestors consumed provide protection from the common cancers that are prevalent in western populations. The available evidence shows that prior to westernization the Inuit and a variety of endemic African cultures had very low cancer rates. I have summarized these papers in my most recent popular book, The Paleo Answer (Chapter 13) and have provided the references.

My feeling is that a distinction needs to be made between free and bound IGF-1. In the literature, this distinction is not always apparent. Hence the IGF-1/IGFBP-3 ratio may be more useful, but may not completely tell the storyr as you know there are 6 IGF-1 binding proteins. So, the most important question would be do high protein diets elevate free or bound IGF-1 in relation to all of the 6 binding proteins. Hopefully, one of my colleagues may be able to provide this answer or give additional input.

Loren Cordain, Ph.D., Professor Emeritus

Ben Balzer (Colleague):

Dear Loren,

Thank you kindly for including me in this discussion. I will give you a totally pro-Paleo point of view, which while digressing from mainstream medicine is totally justified according to the several thousand hours of reading I have done over the past 12 years. My every day practice of medicine is orthodox, but unfortunately I know that it is all obsolete, I feel I am merely painting over rust. The Paleo diet holds the answers to prevent the rust in the first place.

To Shalin, I simply have to say that EVERY paper in nutrition is a paper on Paleo diet, you just have to put on your "Paleo goggles" when you read it.

This is because the Paleo diet includes most of the standard features universally accepted as being beneficial in diet= low GI, high omega 3, low omega 6, high in vitamins, high on fibre etc etc.

So every paper on omega 3 is a paper on Paleo, every paper on fibre/fiber is a paper on Paleo, every paper on dietary intake of vitamins is a paper on Paleo, you just need to adjust your "Paleo goggles".
Now I am very serious when I say this, particularly about cancer. Because modern medicine is about as close to explaining cancer, arthritis, and most other common epidemics, as we were to explain pneumonia in 1700. Really our understanding is empirical. Just as our understanding of pneumonia was empirical but when wediscovered bacteria it became rational.

There is not enough research funding in nutrition, so one must pummel the data to glean what one can. In over a decade, I have never found Paleo wanting. The one major exception to beware of is iron overload. It is a high iron diet (as many diets are). I support the notion of universal iron studies as recommended by the late Victor Herbert and by// particularly in cancer sufferers as iron overload is the classical oxidative stress disease with chronic massive free radical burden (and proven increase in liver and bowel cancer and melanoma). Genetic haemochromatosis is a mutation which makes sense from a Paleo perspective as the modern diet has 1Ž4 of the iron of a Paleo diet. So the heterozygotes and homozygotes have enough iron for growth as an infant, and for a safe pregnancy and breast feeding (the majorinflexion points of survival).

Forget all your old assumptions. You must firstly remember that primitive hunter-gatherers have an ultra low incidence of cancer, and experts like Loren and Staffan have done plenty of work to demonstrate that their diet is a major part of this (along with exercise, vitamin D etc).

In fact one of the major reasons I eat Paleo is because I want to reduce my risk of cancer.

As to established cancer? Unfortunately what can be done cannot always be undone, but it does stand to reason that the diet that is best at preventing cancer should be the best at slowing it down and at preventing recurrence. And everyone has to eat, so they may as well eat the best diet possible.

Name a factor affecting cancerogenesis and look from a Paleo view:
- immune system- function improved by increased omega 3 decreased omega 6, reduction in leaky gut.
- oxidative stress- reduced significantly by the huge levels of antioxidants of all types in the diet.
- Omega 3's- long proven to maintain weight in some cancer patients
- Etc

I've attached a couple of emails from the Paleoscience list (you are welcome to subscribe) which cover some of these issues. I don't hold back, as Paleo is the paradigm which is taking over and I have no time to apologise to oldguard theories. Forget about genetics and proteomics, they are more red herrings. If everyone smoked then epidemiologists would tell us that lung cancer is a genetic disease (reference<//>), but we know it is not true. Similarly everyone eats a Neolithic disease which is more cancer promoting than smoking (studies show that the Kitavan huntergatherers have a high level of smoking but a low level of cancer and ischaemic heart disease)(Staffan did those studies, I hope he doesn't think I've gone too far in reinterpreting them). Proteomics is interesting but is merely an intermediate pathology between diet and cancer. Free IGF-1 is a criticalintermediate pathology, and I feel rather confident that a Paleo diet would be one of the most efficient and effective ways to drop it.

Once you have your Paleo goggles on, then you are using the most powerful model in nutrition today, one that will completely surpass the others, and make everything come together with consummate ease. It is rather like going back to Ancient Rome. A 15 year old could out calculate the greatest minds of Ancient Rome using Hindu Arabic arithmetic, as they had to use Roman numerals. Similarly you are nowfamiliar with a new and more powerful paradigm of health. Do you have the courage to use it when everyone else is using outmoded theories? It's not easy to go against the crowd, but thankfully we now have a big Paleo crowd.

Best wishes,
Ben Balzer

Dr. Cordain:

Thank you Ben,

Your insight is even refreshing for someone who has been immersed in Paleo for much of my career. Here is a list of references which show cancer to be rare in hunter gatherers and less westernized populations, which typically consume higher protein, low glycemic load, low salt, high n-3, and high fruits and vegetables.

Bulkley JL. Cancer among primitive tribes. Cancer 1927;4:289-295.
Capaso LL. Antiquity of cancer. Int J Cancer 2005;113:2-13.
David AR, Zimmerman MR. Cancer: an old disease, a new disease or something in between? Nat Rev Cancer. 2010 Oct;10(10):728-33
Eaton SB et al. Women's reproductive cancers in evolutionary context. Quart Rev Biol 1994;69:353-67
Friborg JT, Melbye M. Cancer patterns in Inuit populations. Lancet Oncol. 2008 Sep;9(9):892-900.
Halperin EC. Pale-oncology the role of ancient remains in the study of cancer. Perspect Biol Med 2004;47:1-14.
Hearsey H. The rarity of cancer among the aborigines of British Central Africa. Brit Med J, Dec 1, 1906, 1562-63.
Henson, WW. Cancer in Kafirs: suggested cause. Guy's Hospital Gazette, March 26, 1904, 131-133.
Hildes JA, Schaefer O. The changing picture of neoplastic disease in the western and central Canadian Arctic (1950-1980). Can Med Assoc J 1984;130:25-32.
Kelly J, Lanier A, Santos M, Healey S, Louchini R, Friborg J, Young K, Ng C. Cancer among the circumpolar Inuit, 1989-2003. I. Background and methods. Int J Circumpolar Health. 2008 Dec;67(5):396-407.
Lanier AP, Bender TR, Blot WJ, Fraumeni JF Jr. Cancer in Alaskan Natives: 1974-78. Natl Cancer Inst Monogr. 1982;62:79-81
Rabinowitch IM. Clinical and other observations on Canadian Eskimos in the Eastern Arctic. Can Med Assoc J 1936;34:487-501.
Renner W. The spread of cancer among the descendants of the liberated Africans or Creoles of Sierre Leone. Brit Med J, Sept 3, 1910, 587-589.
Riveros M. First observation of cancer among the Pampidos (Chulupi) Indians of the Paraguayan Chaco. Int Surg 1970;53:51-55.
Stefansson V. Cancer: Disease of Civilization? Hill and Wang, NY, 1960.
Urquhart JA. The most northerly practice in Canada. Can Med Assoc J. 1935;33:193-196.

Thanks for everybody's input, and hopefully this information will prove to be clinically relevant for Dr. Shalin.

Loren Cordain, Ph.D., Professor Emeritus

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