Welcome to Q&A Mondays! Each Monday, I'll endeavour to answer some of the health questions sent in by readers via email, or that have been posted on the Nutrition by Nature Facebook page.
This week, Stuart asks via email:
The proponents of calorie restriction, and intermittent fasting state that it reduces the levels of circulating IGF-1 [Insulin-like Growth Factor 1], which gets upregulated by a "high protein" diet. The higher levels of IGF-1 apparently lead to a shorter lifespan, and increase your risk of tumour (according to animal studies anyway).
A) Do you believe this is true, despite these methods going against having a high metabolism?
B) Is IGF-1 secreted independently of insulin, and mainly in response to protein intake?
The proponents of calorie restriction, and intermittent fasting state that it reduces the levels of circulating IGF-1 [Insulin-like Growth Factor 1], which gets upregulated by a "high protein" diet. The higher levels of IGF-1 apparently lead to a shorter lifespan, and increase your risk of tumour (according to animal studies anyway).
A) Do you believe this is true, despite these methods going against having a high metabolism?
B) Is IGF-1 secreted independently of insulin, and mainly in response to protein intake?
Thanks for the intelligent question, Stuart!
I’ll tackle part B) first:
Factors that are known to affect IGF-1 levels are GH secretion and sensitivity, genetic make-up, time of day, age, sex, exercise, estrogen status, stress hormones, nutrition status, protein intake, BMI, disease state and xenobiotic intake. This should highlight that there are many, many different variables at play in the determination of IGF-1 levels in the human body.
Like you hinted at, the effect of calorie restriction on IGF-1 serum levels has less to do with insulin and carbohydrate intake (IGF-1 may actually be reduced by increasing carbohydrate intake), and more to do with protein intake, if you’re talking macronutrients and IGF-1. Lower IGF-1 levels have been associated with low-protein diets, although levels appears to only manifest in humans when protein intake is not much higher than the Recommended Dietary Allowance (don’t go restricting your protein intake or turning vegan on me just yet – more on protein intake in a minute).
As for part A)
Yes, reduced IGF-1 levels have been linked to increased lifespan and reduced risk of tumour development (or existing tumour growth) in a number of animal studies. These are cited by proponent of calorie restriction, who claim that calorie restriction and reduced IGF-1 levels are the ticket for living a longer, cancer-free life. However, conflicting results were obtained in the longest calorie-restriction study performed on rhesus monkeys and suggested that in fact calorie restriction makes zero impact on either lifespan or cancer risk.
However, say you were to take the former studies and assume that reducing IGF-1 levels and caloric intake would help prolong life. Firstly, like mentioned above, IGF-1 levels are related to (among many other variables) protein intake, with higher dietary protein correlating with increased IGF-1 levels. This throws question as to whether caloric restriction (or restriction of all the macronutrients) is warranted for the desired effect of increased lifespan and reduced cancer risk. Any benefit of caloric restriction might be attributed to an isolated factor (or many) of the diet – say, restriction of unsaturated fatty acids, excess iron, or indeed, “protein”.
(Don’t assume that reducing IGF-1 levels is a good thing either. IGF-1 promotes protein retention and supports the growth and maintenance of the internal organs, bones and cartilage – humans with IGF-1 deficiencies are categorized as having Laron syndrome (dwarfism) and low IGF-1 levels are related to reproductive impairments and increased bone loss.)
And onto the matter of protein.
Similarly, just like total caloric intake is a fairly non-specific measure in any study (caloric intake might encompass a wide range of macronutrients or huge variations in diet quality), “protein” itself is a broad term that describes highly variable compositions of individual amino acids, and a macronutrient that undoubtedly will be ingested with a multitude of other macro-, micro- and phyto-nutrients attached to it in the context of a “whole food”, the sum of which, and more, will influence any particular protein’s effect in the human body.
Ray Peat suggests that you can achieve the same “life extending” results by restricting certain isolated amino acids like methionine, cysteine and tryptophan, rather than restricting total protein intake, or balancing them with other amino acids such as glycine to help negate any life-shortening or inflammatory effects (I recommend balancing muscle meats with glycine-containing proteins, eg consuming meat along with glycine-rich bone broth, or favouring gelatinous meats such as osso buco over large amounts of lean muscle meats as primary protein sources).
You mention metabolism.
We know that metabolism or metabolic rate falls in ageing, and that a feature of both ageing and degenerative disease is a preference towards using fatty acids for fuel rather than the mitochondrial oxidation of glucose. Anything that restricts metabolism or inhibits oxidative metabolism, such as fasting, low carb diets, or severe caloric restriction, would not be conducive to prolonging lifespan.
A few more strikes against caloric restriction:
A note on intermittent fasting (since I realize most of the above pertains to overall caloric restriction rather than intermittent, “temporary” restriction):
Just like long-term caloric restriction, fasting is ultimately stressful to the body. Fasting and hypoglycemia promote the use of fatty acids for fuel over glucose just like is seen in ageing, low metabolism and degenerative disease, and in particular elevates stress hormones (adrenaline and cortisol) which further contribute to reduced metabolism, increased inflammation, accelerated tissue ageing and reduced overall health. Fasting is particularly harmful if the diet is generally low in carbohydrates and liver glycogen stores are inadequately prepared for periods without food (this can be a problem even when you're talking about the nightly 'fast' between dinner and breakfast, let alone abstaining from food for any longer), and unfortunately intermittent fasting seems to be most popular amongst low-carb dieters.
Fasting differs from overall caloric restriction, as many IF-ers eat plenty of calories, just in a smaller time frame, which can be even more disruptive to blood sugars levels, glucose tolerance and stress hormone levels (which are released to combat hypoglycemia). There’s such a thing as the “catecholamine honeymoon” (thanks, Matt Stone), which means whilst you might feel brilliant riding the initial adrenaline wave that comes from a fast (or a low carb diet, for that matter), you’ll eventually crash and burn when the full metabolic effects of nutrient restriction and chronically elevated stress hormones kick in.
For females in particular, there’s research that shows that intermittent fasting is particularly dangerous. You might want to check out Stefani’s post on the dangers of intermittent fasting for women.
Whew! That was a long response, and probably longer than I had in mind when I was formulating the idea for “Q&A Mondays” in my head. In future, the number of questions I’ll tackle will vary according to the depth and magnitude of the specific questions asked (I’ll answer a few short questions together, or just select one if it requires a much longer response).
Fire through questions for next Monday’s post to [email protected]. Thanks!
I’ll tackle part B) first:
Factors that are known to affect IGF-1 levels are GH secretion and sensitivity, genetic make-up, time of day, age, sex, exercise, estrogen status, stress hormones, nutrition status, protein intake, BMI, disease state and xenobiotic intake. This should highlight that there are many, many different variables at play in the determination of IGF-1 levels in the human body.
Like you hinted at, the effect of calorie restriction on IGF-1 serum levels has less to do with insulin and carbohydrate intake (IGF-1 may actually be reduced by increasing carbohydrate intake), and more to do with protein intake, if you’re talking macronutrients and IGF-1. Lower IGF-1 levels have been associated with low-protein diets, although levels appears to only manifest in humans when protein intake is not much higher than the Recommended Dietary Allowance (don’t go restricting your protein intake or turning vegan on me just yet – more on protein intake in a minute).
As for part A)
Yes, reduced IGF-1 levels have been linked to increased lifespan and reduced risk of tumour development (or existing tumour growth) in a number of animal studies. These are cited by proponent of calorie restriction, who claim that calorie restriction and reduced IGF-1 levels are the ticket for living a longer, cancer-free life. However, conflicting results were obtained in the longest calorie-restriction study performed on rhesus monkeys and suggested that in fact calorie restriction makes zero impact on either lifespan or cancer risk.
However, say you were to take the former studies and assume that reducing IGF-1 levels and caloric intake would help prolong life. Firstly, like mentioned above, IGF-1 levels are related to (among many other variables) protein intake, with higher dietary protein correlating with increased IGF-1 levels. This throws question as to whether caloric restriction (or restriction of all the macronutrients) is warranted for the desired effect of increased lifespan and reduced cancer risk. Any benefit of caloric restriction might be attributed to an isolated factor (or many) of the diet – say, restriction of unsaturated fatty acids, excess iron, or indeed, “protein”.
(Don’t assume that reducing IGF-1 levels is a good thing either. IGF-1 promotes protein retention and supports the growth and maintenance of the internal organs, bones and cartilage – humans with IGF-1 deficiencies are categorized as having Laron syndrome (dwarfism) and low IGF-1 levels are related to reproductive impairments and increased bone loss.)
And onto the matter of protein.
Similarly, just like total caloric intake is a fairly non-specific measure in any study (caloric intake might encompass a wide range of macronutrients or huge variations in diet quality), “protein” itself is a broad term that describes highly variable compositions of individual amino acids, and a macronutrient that undoubtedly will be ingested with a multitude of other macro-, micro- and phyto-nutrients attached to it in the context of a “whole food”, the sum of which, and more, will influence any particular protein’s effect in the human body.
Ray Peat suggests that you can achieve the same “life extending” results by restricting certain isolated amino acids like methionine, cysteine and tryptophan, rather than restricting total protein intake, or balancing them with other amino acids such as glycine to help negate any life-shortening or inflammatory effects (I recommend balancing muscle meats with glycine-containing proteins, eg consuming meat along with glycine-rich bone broth, or favouring gelatinous meats such as osso buco over large amounts of lean muscle meats as primary protein sources).
You mention metabolism.
We know that metabolism or metabolic rate falls in ageing, and that a feature of both ageing and degenerative disease is a preference towards using fatty acids for fuel rather than the mitochondrial oxidation of glucose. Anything that restricts metabolism or inhibits oxidative metabolism, such as fasting, low carb diets, or severe caloric restriction, would not be conducive to prolonging lifespan.
A few more strikes against caloric restriction:
- The subjects of Ancel Key’s calorie restriction study, who were consuming a mere 1,700 calories a day, had such chronically elevated levels of adrenalin that by the end of the study they were almost completely unresponsive to adrenaline injections (read: complete adrenal burnout). Chronic excessive exercise also raises stress hormones and adds to the burden of caloric restriction.
- Another downside to caloric restriction is its propensity to foster eating disorders, particularly in young women (Matt Stone has pointed out that eating disorders are the deadliest known psychological diseases and globally have killed more people than the Holocaust).
- It depends on what you think to be important I suppose, but since I talk to people daily about food and I kind of love the stuff myself: even if caloric restriction did promote a slightly longer life (which at this point I think is probably unlikely), is calorie restriction for life, really a viable prospect? I mean, what’s a few extra years if most of your life is lived semi-starved, excessively lean and hungry – all of which have other physiological and psychological consequences. Chronic undernutrition will definitely make you look, feel and act prematurely old.
A note on intermittent fasting (since I realize most of the above pertains to overall caloric restriction rather than intermittent, “temporary” restriction):
Just like long-term caloric restriction, fasting is ultimately stressful to the body. Fasting and hypoglycemia promote the use of fatty acids for fuel over glucose just like is seen in ageing, low metabolism and degenerative disease, and in particular elevates stress hormones (adrenaline and cortisol) which further contribute to reduced metabolism, increased inflammation, accelerated tissue ageing and reduced overall health. Fasting is particularly harmful if the diet is generally low in carbohydrates and liver glycogen stores are inadequately prepared for periods without food (this can be a problem even when you're talking about the nightly 'fast' between dinner and breakfast, let alone abstaining from food for any longer), and unfortunately intermittent fasting seems to be most popular amongst low-carb dieters.
Fasting differs from overall caloric restriction, as many IF-ers eat plenty of calories, just in a smaller time frame, which can be even more disruptive to blood sugars levels, glucose tolerance and stress hormone levels (which are released to combat hypoglycemia). There’s such a thing as the “catecholamine honeymoon” (thanks, Matt Stone), which means whilst you might feel brilliant riding the initial adrenaline wave that comes from a fast (or a low carb diet, for that matter), you’ll eventually crash and burn when the full metabolic effects of nutrient restriction and chronically elevated stress hormones kick in.
For females in particular, there’s research that shows that intermittent fasting is particularly dangerous. You might want to check out Stefani’s post on the dangers of intermittent fasting for women.
Whew! That was a long response, and probably longer than I had in mind when I was formulating the idea for “Q&A Mondays” in my head. In future, the number of questions I’ll tackle will vary according to the depth and magnitude of the specific questions asked (I’ll answer a few short questions together, or just select one if it requires a much longer response).
Fire through questions for next Monday’s post to [email protected]. Thanks!
Kate is a certified Clinical Nutritionist and offers one-on-one coaching for clients in Sydney Australia, and internationally via Skype or email. Visit the nutrition services page to find out more about private coaching, and be sure to subscribe via email and follow the Nutrition by Nature Facebook page for blog updates, articles, nutrition tips, recipes and special offers.
