What is the ideal IGF-1 level for longevity?

[Gordo]

I have never had my IGF-1 tested, but would like to do so.  Anyway, I stumbled upon this commentary today from Dr. Joel Fuhrman where he says for LONGEVITY the ideal IGF-1 is between 100-150 ng/ml, not the >200 most American's have, and below 80 is bad:

 

He also talks about changing protein requirements as we age, <80 you probably only need 0.8g/kg (40-50g protein/day for most people), over 80 you may need up to 50% more protein (about 70g for a 150lb person).  He eats animal products a few times a year:

[mccoy]

Gordo, that's a good topic I wanted to open a thread with but you preceded me. I remember Dr. Peter Attia in his shownotes of Dr. Barzilai's interview posted an asymmetrical U-curve, but the shownotes are now open only to the subscribers, I don't know if anyone here has access to those notes. Also Valter Longo said something in his Stemtalk interview but I don't remember if it was a quantitative or qualitative value. His contention is that after about 65 people must eat more protein to increase IGF-1, or else they have to exercise every day to avoid sarcopenia.

[mccoy]

There is also the issue of systemic (plasma) concentration of IGF-1 versus the local concentration in muscle tissue and CNS tissue, the latter tissues benefitting from consistent IGF-1 concentrations.

[mccoy]

A good discussion on IGF-1 by colin Champ MD (I didn't know him previously). Probably one of the most exhaustive IGF-1 discussions available. Couldn't find references to an optimum value though

http://colinchamp.com/igf-1-cancer/

Quote

urthermore, during and after exercise, IGF-1 is pulled from the blood and into the brain to support its function,⁷⁸ one of the many ways in which exercise improves cognition. In fact, the benefits of exercise-derived IGF-1 are so strong that if we block IGF-1 uptake into the brain, it eliminates the cognitive and neuroprotective benefits of exercise.⁷⁹

Exercise signals to many IGFBPs to release their IGF-1, which is then used to promote muscle growth and repair. The remaining IGF-1 then becomes bound again as levels drop back to normal. It is as though we can exercise off excess IGF-1. Also, much like the way in which exercise pulls sugar from our blood and into our cells to be burned as fuel, improving our insulin sensitivity, the same may be true of exercise and IGF-1.

On the other hand, IGF-1 levels naturally decrease in the elderly, which can lead to multiple health issues, prompting attempts to increase them. Exercise⁸⁰ and increased protein consumption⁸¹ in the elderly can increase levels of IGF-1 and improve their health, including decreasing risk of cancer and improving cognition.

 

Conclusions: Exercise has many benefits, but its effect on IGF-1 remains relatively unclear. It transiently raises our IGF-1, and seems to “push” IGF-1 to our brain and muscles to improve the function of both. Exercise and protein consumption can benefit the elderly by raising IGF-1.

 

 

[Saul]

3 hours ago, mccoy said:

His contention is that after about 65 people must eat more protein to increase IGF-1, or else they have to exercise every day to avoid sarcopenia.

Yes; this is a common contention.

However, one's biological age may not be the same as one's chronological age.  I try to keep protein consumption low -- but IGF1 still usually comes out higher than I would like.

Insulin-Like GF-1	123 ng/mL	19 - 189 ng/mL
IGF 1 Z Score Calculation	0.6
INTERPRETIVE INFORMATION: IGF 1 Z-SCORE CALCULATION A Z score is the number of standard deviations a given result is above (positive score) or below (negative score) the age- and sex-adjusted population mean. Results that are within the IGF-1 reference interval will have a Z score between -2.0 and +2.0. Performed by ARUP Laboratories, 500 Chipeta Way, SLC,UT 84108 800-522-2787 www.aruplab.com, Julio Delgado, MD - Lab. Director

   --  Saul

[mccoy]

In your case, the higher than average  value in the same age braket might turn out to be beneficial, since the mean value may reflect the decrease of IGF-1 with age which is associated to lesser longevity, hence a little higher than mean would underline a lack of degradation.

It is all theoretical consideration, since apparently data from different sources are sometimes contrasting.

Laron dwarfs have high IGF-1 but non-functional receptors, so they are immune from cancer and degenerative disease. But too low IGF-1 is notoriously bad and may cause cancer (/same with too high). When low is bad? sure not in a young age. After 65 it's probably bad,  although  reverse causation may exist (in older people). Then there is the IGF-1/IGFBP ratio issue, the issue of systemic (plasma)  versus local (muscles, bones, nervous system) IGF-1.... confusion reigns supreme in my head.

😫😫

Edited March 8, 2019 by mccoy

[Todd Allen]

17 hours ago, mccoy said:

A good discussion on IGF-1 by colin Champ MD (I didn't know him previously).

Colin Champ is an oncologist well known in keto and paleo circles.  Here is a sample of his recommended approach to health.

The Seven Pillars of the Mediterranean Ketogenic Lifestyle

1. Keep carbohydrates low

Any low-carb, ketogenic, or diet that aims to avoid the blood sugar and insulin roller coaster while enacting our body’s cellular mechanisms to recycle their faulty parts and get rid of cellular garbage should include general restriction of carbohydrates. The golden number varies, but nutritional ketosis requires it to be less than 20-50 grams per day, while a very-low and low-carbohydrate diet can range from 0-150 grams per day. Somewhere in this range should work for most people in terms of weight loss/maintenance and activating the cellular benefits that accompany this lifestyle.

When considering carbohydrates, much like with bitter vegetables and other berries full of healthy chemicals like raspberries, blackberries, and blueberries are key. Others will turn to sweet potatoes, yucca, and similar starchy sources, but this will likely boot most people from ketosis. I personally enjoy these foods, but generally consume them after a workout when I am most insulin sensitive (i.e. my body needs less insulin to reduce my blood sugar). I also will eat them most often if I am losing too much weight on the ketogenic diet (yes, this happens).

2. Green, leafy, and colorful vegetables

Eating plenty of leafy greens, colorful vegetables, and cruciferous vegetables is a must, with the goal of having them at every meal. These fibrous vegetables contain a plethora of healthy immune system-stimulating and anticancer chemicals, along with soluble fiber to feed our bowel bacteria. Most of these contain such a low amount of non-fibrous carbohydrates that they can be considered a free pass when it comes to dipping into ketosis. Those that desire to stay deeply in ketosis may have to consider how many colorful vegetables they are consuming, but it depends on the individual.

3. Fat, fat, and more fat

A true ketogenic diet, or even a periodic ketogenic diet relies on plenty of fat. Take a couple hints from the Mediterranean area and eat plenty of high monounsaturated olive oil (make sure it is real and not laced with harmful oxidized vegetable oils), fatty fish with high omega-3 fatty acids, high quality meats, some nuts, and full-fat cheese (the kind that would hang from the ceiling in my great-grandfather’s meat and cheese shop). Heavy cream from grass-fed cows and macadamia, coconut, avocado, and palm oil are great for garnishing and cooking, but if we are turning for them as our main source of fat, we need to turn back towards wholesome, nutrient-dense foods.

4. Replace sweet foods with bitter ones

Bitter foods, like many green and cruciferous veggies, contain chemicals that increase our defense system. Furthermore, they train our taste preferences to shy away from unhealthy sweet foods. Bitter foods are like exercise for your palate, to train it to avoid unhealthy and addictive uber sweet foods. For instance, infants exposed to bitter foods early in life tend to favor them throughout adulthood.²⁰ While the effect is less studied in adults, I have experienced this sensitization myself and so have many of my patients, friends and family members.

Bitter vegetables, garlic, onions, herbs, and bitter red wine all contain a plethora of chemicals that act as an empty threat to increase our cellular defense systems and to activate our antioxidant defense system. Furthermore, they activate our detoxification system to rid our body of potentially harmful and cancerous chemicals, (the same chemicals researchers use to cause cancer in mice).

5. Get plenty of daily activity with periods of intermixed intense activity, resistance training, and lifting heavy things

Any discussion of the benefits of the Mediterranean diet without considering the frequent amount of activity that individuals in the traditional longevity-dense areas of Southern Italy, Greece, and Sardinia experience is missing a major component of their health. There are no elevators and escalators in these hilly communities, and simply walking around provides a muscle-pumping leg work out that becomes exponentially harder when carrying something. Lifting heavy things and contracting your muscles prompts them to release anti-inflammatory and anti-cancer chemicals and hormones and should be part of everyone’s repertoire.

6. Go plenty of periods without food – eat dense foods then no foods

The above-mentioned foods will provide us with plenty of nutrients to function optimally while remaining a healthy weight, but that does not mean we should be eating them all day long. Avoid snacking and aim for longer stretches between meals. This is very prevalent in the real Mediterranean diet, as the Greeks and other groups fast for up to 103 days per year, providing a handful of benefits like improved heart health,^21–23 improved brain health,²⁴ and potential anticancer effects²⁵ (initial Mediterranean diet studies left out all discussion of fasting²⁶). Increasing periods without any food will lower blood glucose and insulin, while activating autophagy, which signals our cells to get rid of any clutter or junk.

7. Triple R’s: Rest, Relaxation, and Recovery

In modern society’s go, go, go atmosphere, we forget that following a healthy lifestyle is more than just our food and activity. The times when we are not eating or exercising refuel our body to recover from exercise and replenish our muscles, while high quality and adequate sleep help promote a healthy metabolism to deal with the foods we eat, maintain a low/normal blood sugar level, and keep our mitochondria functioning optimally to help fight disease. Furthermore, socializing, reading, and other hobbies allow your body to relax while exercising your mind, providing even more benefits than simply refueling. Other activities, like tending a garden, allow us to turn our minds off. Just as the body needs recuperation times, so does the mind (and no this does not include watching television).

 

The above seven pillars of the Mediterranean Ketogenic Lifestyle have worked well for me to maintain a healthy weight and lifestyle, while keeping my body and mind replenished. I recently spent some time in San Lorenzo Bellizzi, after my wife and I crossed the entirety of Southern Italy in a week to gather some documents from my family villages etched high in the mountain in Italy. The physically exhausting trip provided an up close and personal view of how these principles were unintentionally followed in the past by my family and how, with a little modification, can be used to attain a healthy lifestyle, that is both easy and fun to follow. With the steep cliffs, sheep, vineyards, and olive groves in sight, it was easy to imagine Leonardo Pesce, my great-grandfather, scaling the cliffs as he walked with his flock of sheep, helping to feed his family and the town with his full fat cheese. While parts of his diet would certainly violate the pillars of a Mediterranean Ketogenic Lifestyle, the large proportion of similarities are uncanny. Furthermore, by continuing many of his traditions when it comes to meat and cheese preparation, I think he would be proud that his true Mediterranean culture is being endorsed to promote a healthy lifestyle a century later.

 

And an excerpt from the end of his book Misguided Medicine which questions conventional wisdom on nutrition and medicine:

Nothing makes me recall the story of Laocoön more than present-day science and medicine – particularly nutrition. Those that question the norm get lambasted, punished, and even disbarred; though they may often be right, we might as well entangle them with snakes and drown them. The nutrition world has suffered the worst in the form of their flagship Trojan Horse known as the Food Pyramid. Those nutritionists that have dared to questioned it and challenge conventional “wisdom” have long been thrown to the serpents, much like Laocoön. However, we now see that the Food Pyramid narrative – much like Sinon’s tall tale – has been based on little scientific backing.
Laocoön was punished – not for being right, but for questioning the wisdom of the mob. This is one of the oldest tales in recorded history warning us of the dangers of questioning the narrative and casting doubt on the stories society repeats. Society gets angry. Gods get angry. Snakes are sent from the sky to coil around your arms and torso, puncture your flesh, inject deadly venom, and pull you into the sea for a wretched death.

Most would consider that Laocoön lost in the long run. After all, he was forced to endure watching his children drown as massive snakes tore their bodies apart. Yet despite this misery, Laocoön and his sons made such an impact to his contemporaries that all three have been commemorated in a majestic marble statue that is now considered one of the most beautiful and well-kept in the world. Laocoön – muscular, vascular, and symmetric, to an elevated degree that is difficult to believe existed in artisan minds 2,000 years ago – has the look of agony that is forever eternalized in those that experience the statue. It remains fully intact and in remarkable condition at the Vatican in Rome, well-preserved throughout the ages. It has been referred to as the “prototypical icon of human agony.”

While death by serpentine drowning was certainly a steep penalty for questioning the established narrative, one can certainly argue that immortalization via one of the most beautiful works of art in human existence may have been worth that price. As difficult as it may be during those precise moments of intense scrutiny cast upon those who question the stories of the uninformed masses, they should not shy away from doing so, because their conviction may one day place themselves side by side with Laocoön –  nobly ensconced on the right side of the truth and praised by generations to come.

The enduring takeaway from Laocoön’s trials and tribulations is the importance of questioning dubious narratives: such brazenness may very well anger the gods, but may eventually save the city from that Trojan Horse.

Edited March 8, 2019 by Todd Allen

[mccoy]

Thanks Todd for the reference, the rationale that fat does not spike blood glucose nor IGF-1 has undoubtedly some value, although a lot of fat is known to carry potential big issues.

When everyone says the opposite of everyone else, I'll base my choices on the Bayesian method: subjective belief (prior) , corroborated or negated by evidence (data from blood analyses and more measurements). 

 

[Todd Allen]

2 hours ago, mccoy said:

corroborated or negated by evidence (data from blood analyses and more measurements). 

Although there is much controversy about what constitutes an optimal profile both across populations and with respect to individuals.

In my case 3 years ago before I began caloric restriction, fasting, keto, thermal stress and frequent brief high intensity strength training my testosterone and LDL were a little above their reference ranges, alarming for someone with a genetic untreatable wasting disease the rate of progression of which is strongly believed to be directly proportional to ones level of testosterone and with dyslipidemia, hypertension and CVD somewhat correlated to disease progression.  Medications kept my blood pressure within the stage 2 hypertension range.  During my early rapid weight loss phase my testosterone briefly dipped into the reference range but now has surged to nearly double the level before I started.  My LDL is now almost double the reference range.  My HDL has nearly tripled.  Triglycerides are down by 2/3rds.  My IGF-1 is nearly 10 times higher and should soon be above the reference range.  My blood pressure is now normal without medication.

My previous doctor was stunned and thrilled with the changes in my biomarkers and health.  Unfortunately due to a change in insurance I have a new doctor horrified my bloodwork continues moving in the "wrong direction", despite me being a 54 year old man with a genetic untreatable progressive wasting disease regaining muscle mass, strength and fitness at an increasing pace.  If professionals can have such widely differing opinions about what is desirable it's not surprising the rest of us are confused too.

Edited March 8, 2019 by Todd Allen

[mccoy]

Todd, yours is a specific case, as yourself have made clear so far. Since you must struggle against a little-known muscle-wasting disease, it makes sense that you benefit from an high percentile of IGF-1, which is known to contribute to muscle anabolism. I understand that sometimes doctors are worried about legal liabilities, so if markers go beyond some official threshold they might be worried.

 

[Sibiriak]

 

Michael Rae:

https://www.crsociety.org/topic/11708-blood-testing-lef-super-sale-—-ends-june-13th/?tab=comments#comment-19478

Posted November 9, 2016

-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

[...]   the whole point of getting both [ IGF-1 and IGFBP-3 tests] is to assess the biological activity of your IGF-1: a higher level of IGFBP-3 at a given IGF-1 level (hence, a lower IGF-1:IGFBP-3) means less free IGF-1 and lower biological activity. (Note that this is not the case for IGFBP-1, which has a more complex role in the pathway).

IAC, there is an additional and important underlying question, which is the way these tests are reported in American labs. The sensible way to report both IGF-1 and IGFBP3 is in (nano)moles per unit volume, which then tells you about biological relationships between the functions of the proteins.This is why every country in the world except the United States uses molar units. Unfortunately, the US reports them as mass per unit volume, which skews everything because of the different molar masses of the different analates.

You can convert your reported values to molar values and ratio as follows:

IGF-1 (molar concentration) = [iGF-1 [ng/mL] x 0.130

IGFBP-3 (molar concentration) = IGFBP-3 [ng/mL] x 0.036

IGF-1:IGFBP-3 = [iGF-1 [ng/mL] x 0.130]/[iGFBP-3 [ng/mL] x 0.036].

(Incidentally: altho' IGFBP-3 isn't on it, the AMA has a good calculator to convert American lab test units to SI units).

Importantly, the key Aging Cell paper (1) on protein intake and IGF-1 in human CR practitioners, which is probably our best guide on CR-specific reference ranges, uses molar units:

 

 

The "low protein" group in these graphs is a vegan group not intentionally CRed; the "low Calorie" group is the original data from the full CR cohort, including the majority who were getting protein intakes were well in excess of the RDA. We presumably want an IGF-1 level in line with the CR group after reducing their protein intake to RDAish levels (0.95 mg/kg), which was 152 ± 41 ng/mL; or possibly low-normal IGF-1 either for a young person or for our age group.

 

Whatever range of IGF-1 one targets. we presumably want an IGF-1:IGFBP-3 in line with the "low protein" group above.

 

Reference

1: 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. PubMed PMID: 18843793; PubMed Central PMCID: PMC2673798.

Edited April 17, 2019 by Sibiriak

[mccoy]

I'm going to paste here from another thread a series of table on IGF-1 concentrations that I came up with after hearing the Hyman-Longo interview, where Longo said that the optimum concentration  is 140 ng/dL :

140 seems to be ideal, whether you're young or old.  Now it could be very old that it may not be that easy to keep 140, but in general, in the adult population, 140 seems to be ideal.

The above sounds strange. If IGF-1 peaks at about 20 then it trends rapidly down, I had this curiosity to look up some statistical data. I couldn't find any western database though.

[mccoy]

If we knew what's the optimum IGF-1 serum concentration for the various ages we'd be able to check our individual levels with such optimum.

Longo in his interview with Hyman said 140 ng/mL, but provided no age reference.

In this article, the Brazilian population is tested with the following results (no male-female differences)

 

Chinese population:

[mccoy]

The above units are all mass/volume, so it makes sense that they are the same units used by Longo (american usage). 140 ng/dL is:

• The mean of the Brazilian population at age about 50
• The mean of the Chinese population at age about 47
• The mean of the Arab population at age about 40

That would also imply that on the average, Brazilians at 50, chinese at 47, Arabs at 40 have an optimum serum level of IGF-1 and, going on further with the cited ages, they should strive to increase such IGF-1 (NOT practicing CR, eating more proteins/methionine).

Also, all young men below said ages have too low a serum level of IGF-1 hence should strive to do the opposite of Brazilians at 50, chinese at 47, Arabs at 40.

[mccoy]

In this study they compare control population to TM patients, this is supposed to be a Western-population database.

 

According to the above reference range, 140 ng/dL is the average value at age of about 53

[Sibiriak]

 A few points:

1) According to Michael Rae and others,  IGF-1 measurements alone are not really informative;  you also  need  to look at the IGF-1/ IGFBP-3 ratio  to assess the biological activity  of the IGF-1 [" a higher level of IGFBP-3 at a given IGF-1 level (hence, a lower IGF-1:IGFBP-3) means less free IGF-1 and lower biological activity."   https://www.crsociety.org/topic/11708-blood-testing-lef-super-sale-—-ends-june-13th/?tab=comments#comment-19478

 

2) Michael Rae:

Quote

[MiamiNice:]  I have read that there is a trade off when it comes to growth hormone and IGF-1 & Longevity . Growth hormone and IGF-1 enhance muscle and cognitive performance but this comes at a cost: longevity. Reduced growth hormone and IGF-1 increase lifespan by increasing the expression of genes involved in stress resistance but at an expensive cost when it comes to muscles and brain.    What good is it to live longer if the price is muscular frailty & decreased cognition?  How do CR members arrive at a compromise. ]

[Michael Rae: ]The super-short version is that the way you've phrased the dilemma is somewhat oversimplified. IGF-1 boosts brain and muscle in the short term, but in the long term most-but-not-all animal studies and studies of people with genetic IGF-1 signaling deficits suggest that it actually accelerates their decline. There's also the issue that IGF-1 levels tend to decline late in life due to the aging process itself, whereas they stay steady but low on CR or in IGF-1 mutant mice, and these are quite different physiological states. There may be an advantage to boosting them up in people whose IGF-1 levels have declined as a result of aging (I mean people in their last decades, not middle-aged people), though clinical trials have not largely supported the idea, but that's quite different from sustaining high levels thru' the rest of one's life. See for instance here and here.   (blue emphasis added)

https://www.crsociety.org/topic/16865-trade-off-between-growth-hormone-igf-1-vs-longevity/?tab=comments#comment-29617

 

3) Based on the 2008 Fontana study (see my post above, Wed. 2:26PM), Michael Rae states:

Quote

We presumably want an IGF-1 level in line with the CR group after reducing their protein intake to RDAish levels (0.95 mg/kg), which was 152 ± 41 ng/mL; or possibly low-normal IGF-1 either for a young person or for our age group.  Whatever range of IGF-1 one targets. we presumably want an IGF-1:IGFBP-3 in line with the "low protein" group above.

https://www.crsociety.org/topic/16981-what-is-the-ideal-igf-1-level-for-longevity/?tab=comments#comment-31161

 

Edited April 20, 2019 by Sibiriak

[mccoy]

Sibiriak, then you agree that Longo seems to have oversimplified the issue. 

The above suggestions from MR should be evaluated with attention. 152 ± 41 ng/mL is not a low concentration, higher than the 140 average value cited by Longo.

Whereas, when MR goes 

Quote

or possibly low-normal IGF-1 either for a young person or for our age group.

That in statistical terms means a value probably located around the  30th percentile of the general population distribution per age group. Or the mean minus  SD.

SO, in the plot I posted above and again posted here, that means one value which is found between the yellow line and the pale blue line underneath it.

For example, if we take the 50 years age group, according to teh above suggestions, our IGF-1 should be located in the 100-150 ng/mL range. Which is what Fuhrman in the original OP cited, without an age specification though.

Then we should cross-check by the IGF-1:IGFBP-3 ratio...

Edited April 20, 2019 by mccoy

[mccoy]

Then, there is the issue of optimal IGF-1 levels for older people, 'in their last decades', which appears to be another different aspect...

[mccoy]

This is the specific post by Dr. fuhrman, with papers citations, with age groups and quantities

 

Optimal IGF-1 levels

A meta-analysis analyzed ten studies on IGF-1 levels and all-cause mortality. The authors found a “U-shaped” association, meaning that IGF-1 levels on the low end and the high end of the spectrum were associated with increased risk of premature death.¹⁴

The lowest risk was at the 55th percentile of serum IGF-1, and increased in both directions for all-cause, cancer, and cardiovascular mortality.¹⁴ This data suggests that we should aim for an IGF-1 level near the lower to middle for healthy people in our age range. A few studies, primarily in European populations, have attempted to define average IGF-1 levels for healthy people in different age ranges:^15-17

Age:	Average Serum IGF-1 (ng/ml)
21-30	158-230
31-40	135-220
41-50	121-193
51-60	98-150
61-70	85-140
71-80	85-95
80+	85-90

These numbers are somewhat lower than the average IGF-1 levels reported in several other studies in U.S. and European populations.

The European Prospective Investigation into Cancer and Nutrition (EPIC) study reported an average serum IGF-1 level of 200-210 ng/ml, suggesting that this is a typical level for adults on a Western diet.¹⁸ The amount of animal products consumed by most Americans drives their IGF-1 into this danger zone (above 200), increasing their risk of cancer.

Two studies comparing adults on a vegan (or raw vegan) diet (9-10 percent of calories from protein, no animal protein) to those on a Western diet (16-17 percent of calories from protein) found the Western diet average IGF-1 level of 200 ng/ml and vegan average lower than 150 ng/ml. One of these studies also evaluated IGF-1 in non-vegan endurance runners, and their average was about 175.^19-20 The average age of subjects in these studies was in the mid-50s.

Low IGF-1 levels associated with an increased risk of disease or mortality are generally about 70-80 ng/ml or lower.^15,21-26Studies in elderly men (average age 75) have found increased risk of cardiovascular events and deaths from cancer in high IGF-1 groups, approximately 190 ng/ml.^22-23

In the Nurses’ Health Study, premenopausal women with IGF-1 levels higher than 207 had a substantially higher risk of breast cancer.^2,7 In the Physicians’ Health Study, there was an increase in prostate cancer risk once IGF-1 increased above 185 ng/ml.²⁸

Taking all of this information into account, for most adults, keeping IGF-1 below 175 ng/ml is likely important, and below 150 ng/ml should be even more protective. Serum IGF-1 levels below 80 ng/ml may be detrimental, especially after the age of 75.

Restricting animal protein during most of one’s adult life to maintain a relatively low, but not excessively low IGF-1, is an important objective for those desiring superior health and life extension.  Protein assimilation can decline in the elderly. The use of greens, seeds and beans in the Nutritarian diet, to assure protein adequacy with aging, prevents the excessive lowering of IGF-1 in the elderly, often seen with other plant-based diets. The attention to micronutrient completeness and plant protein adequacy on a Nutritarian diet makes it the most scientifically supported diet-style to push the envelope of human longevity.

[Sibiriak]

Quote

...Longo seems to have oversimplified the issue.  

Perhaps, though I'd really like  know the reasoning behind that quick statement in the video.

Quote

152 ± 41 ng/mL is not a low concentration, higher than the 140 average value cited by Longo.

A bit higher,  but  not that much given the wide ± 41 range,  and  really not that different from Fuhrman's  claim  that  for most adults below 175 is okay, below 150 being better,  below 80 likely  detrimental  (and none of those three taking into  consideration IGF-1 biological activity measurement.)

 

Quote

 ...That would also imply that on the average, Brazilians at 50, chinese at 47, Arabs at 40 have an optimum serum level of IGF-1 and, going on further with the cited ages, they should strive to increase such IGF-1 (NOT practicing CR, eating more proteins/methionine).

 

But there's Michael Ray's claim  (linked above) that " IGF-1 levels ... stay steady but low on CR or in IGF-1 mutant mice, and these are quite different physiological states"

Besides,  optimizing IGF-1 levels is only one of many different  mechanisms by which CR and/or protein moderation/avoiding animal proteins might increase healthspan and/or  lifespan .

Personally,  unless my IGF-1 (biological activity)  was very low, I wouldn't abandon my current Longo-ish (very) moderate CR/low protein diet.

Btw,  in 2016 Dean Pomerleau reported--

Quote

IGF-1 - 83 (RR 61-200) - Remains nice and low as expected for CR person. But up a bit from last time (71) which is probably a good thing, for brain, bone and cardiovascular health.

https://www.crsociety.org/topic/11215-latest-bloodwork/?page=2&amp;tab=comments#comment-17245

and, if  I recall correctly,  Michael Rae (somewhere) suggested that Dean  might want to consider a modest increase in protein intake.

 

 

Edited April 20, 2019 by Sibiriak

[Sibiriak]

Effects of 2‐year calorie restriction on circulating levels of IGF‐1, IGF‐binding proteins and cortisol in nonobese men and women: a randomized clinical trial

Luigi Fontana et al.

Aging Cell. 2016 Feb; 15(1): 22–27.

Published online 2015 Oct 6. doi: 10.1111/acel.12400

PMCID: PMC4717266 PMID: 26443692

 

Quote

Summary

Young‐onset calorie restriction (CR) in rodents decreases serum IGF‐1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anticancer and anti‐aging effects. However, little is known on the effects of CR on the IGF‐1 system and cortisol in humans. To test the sustained effects of CR on these key hormonal adaptations, we performed a multicenter randomized trial of a 2‐year 25% CR intervention in 218 nonobese (body mass index between 22 and 27.8 kg m⁻²) young and middle‐aged (20–50 years age range) men and women. Average CR during the first 6 months was [only] 19.5 ± 0.8% and 9.1 ± 0.7% over the next 18 months of the study. Weight loss averaged 7.6 ± 0.3 kg over the 2‐years period of which 71% was fat mass loss (P < 0.0001).

Average CR during the CR caused a significant 21% increase in serum IGFBP‐1 and a 42% reduction in IGF‐1:IGFBP‐1 ratio at 2 years (P < 0.008), but did not change IGF‐1 and IGF‐1:IGFBP‐3 ratio levels. Serum cortisol concentrations were slightly but significantly increased by CR at 1 year only (P = 0.003). Calorie restriction had no effect on serum concentrations of PDGF‐AB and TGFβ‐1.

We conclude, on the basis of the present and previous findings, that, in contrast to rodents, humans do not respond to CR with a decrease in serum IGF‐1 concentration or with a sustained and biological relevant increase in serum cortisol. However, long‐term CR in humans significantly and persistently increases serum IGFBP‐1 concentration.

Full text:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717266/

Reinforcing Fontana's 2008 findings discussed above:

Quote

Reducing protein intake from an average of 1.67 g kg −1 of body weight per day to 0.95 g kg −1 of body weight per day for 3 weeks
in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL −1 to 152 ng mL −1 . These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide
evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.

Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673798/

 

Edited April 20, 2019 by Sibiriak

[mccoy]

Where the optimum level according To Valter Longo stands. 140 ng/ml. Plus or minus one standard deviation from the average in the 30 to 80+ age bracket.

From 50 to 60 140 ng/ml is pretty much the average value of the whole male population. starting from about 57 and above, we should have according to Longo, more IGF-1 than the average of the same age.

 

Edited May 8, 2019 by mccoy

[Sibiriak]

Mccoy,  nice graph.   When are you going to get tested, though?     And what about IGFBP-3?

 

 

 

[mccoy]

Sibiriak, thanks and yes, the graph seems to pretty much give logic plausibility to Longo's assertions.

I'm probably going to test IGF-1 next month, as soon as I'm going to renew my health insurance policy. Although IGF-1 is not covered, I'll have it tested on my tab.

IGF-1 alone at this point seems pretty straightforward, if we accept Longo's suggestions (I have no difficulties with that). Whereas including IGFBP-3 makes things more complex and costly., I'll have to think about it maybe planning more tests in the future.

Right now my priority is the old ticker, some cardiovascular preventive exams, cardiac ecography seems to be the best bang for the buck. Plus circolatory exams, they are long due since in my family runs a little propensity for heart problems.

There is also the issue of prostate and colorectal health, which I've been carefully avoiding for years, but I'll have to tackle next.

[Ron Put]

On 3/8/2019 at 7:04 AM, Todd Allen said:

Colin Champ is an oncologist well known in keto and paleo circles.  Here is a sample of his recommended approach to health.

...

1. Keep carbohydrates low....

This is not supported by evidence. Of course, it depends on what kind of carbs (you can't eat cake all day), but overall, good carbs are good. For instance, carbs make up the bulk of calories in diets correlating with longevity. The traditional Okinawan diet, for example, is 85% carbs with 9% protein and 6% fat.

"The lifespans enjoyed by Okinawans may be explained by several genetic, environmental, and lifestyle factors. That said, experts believe that one of the strongest influences is diet.The traditional Okinawa diet is low in calories and fat while high in carbs. It emphasizes vegetables and soy products alongside occasional — and small — amounts of noodles, rice, pork, and fish."
https://www.healthline.com/nutrition/okinawa-diet#the-diet