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IGF1 Measurement
03 Apr 2013, 21:47
So I had a Medichecks 'IF panel' test. Glucose was reasonable (5.1),TRIs good (1.0) and cholesterol stellar (40% HDL). However the fly in the ointment was IGF1 (24.4), within range but in the upper half. That is after over 6 months 52,- unfortunately I don't have a 'before' reading. This makes me wonder if the body 'rebalances' IGF1 to IF after a period (as I've read of CR).

Reading wider it seems the only proven way to influence IGF1 long term is to reduce protein intake, especially milk. I've always followed the advice every meal should have complete proteins, but I'll thing I drop that as an essential, and rely more on coconut milk (which I love).

Be interested to hear of any other measurments.
Re: IGF1 Measurement
03 Apr 2013, 21:55
Yes I've seen research papers that say that calorie restriction alone does not reduce IGF1 in humans and that protein reduction is what is needed. However, IGF1 is not the full story...have a look at my posts on mTOR and FOXO. So I wouldn't get too hung up on IGF1. I agree that cutting down on animal protein is probably a good thing for most of us meat eaters though!
Re: IGF1 Measurement
04 Apr 2013, 07:49
Hi Paul, thanks for posting those figures, they are about the first ones we have had here about IGF-1 levels following 5:2. Disappointing, it does seem that 5:2 is not a 'magic bullet' for reducing IGF1. Did you listen to the recent Radio 4 programme - see the topic here and my 3rd post on the topic.

No advice there though on how to reduce IGF1. It does seem like lower carbohydrate (to keep insulin down) and lower baby food (dairy!) should help. Dr Michael Greger says that vegan diet helps (is he a respected guy?) [and more specifically that a vegetarian diet does not], as does Dr Valter Longo, who also uses these periodic 3-day fasts (as we all saw in the Horizon programme).
Re: IGF1 Measurement
04 Apr 2013, 10:29
The R4 health thing yesterday said something along the lines "it's not the IGF levels it's the reduction in IGF binding proteins" or words to that effect.

Does the analysis give us active / free IGF-1 levels or ??
Re: IGF1 Measurement
04 Apr 2013, 11:03
Well of course its the action at the receptor that will be important. But more important is activity downstream at mTOR really!
Re: IGF1 Measurement
04 Apr 2013, 16:03
here is what they say about IGF-1 in the R4 programme (sorry for the length of it), my transcript and slightly edited:

Dr Val Macaulay, medical oncologist at the Weatherall Institute of Molecular Medicine at the University of Oxford, studies cancer cells in the lab. They require special culture mediums to grow but one set of lung cancer cells seemed to thrive without much help from Dr Macaulay. Analysis showed that this particular culture was absolutely packed full of insulin-like growth factor.

Growth hormone makes us grow, and the reason it does that is that it makes the liver produce IGF-1. So when you have growth hormone production by the brain, that causes the liver to make IGF-1, and that in turn causes your bones and muscles to grow.

So IGF-1 is actually the delivery boy, what makes growth hormone work. And as we are getting better nourished we are kind of setting our ‘IGF-ostat’, as it were, at a higher level.... People with acrimegaly have high levels of growth hormone and high levels of IGF-1 – and they are more prone to cancer... That increased risk is fourfold and more.

What IGFs may be doing is that if someone has a tiny cancer or a few cells that are thinking about becoming abnormal and making a cancer, maybe in someone whose IGF levels are relatively high that may allow the persistence and growth of that cancer - to the point where it is clinically evident and starting to cause problems for the person.

The way that IGFs work is that they stick onto special molecules on the surface of cells called receptors. It’s a bit like if you think of a key going into a lock, the key will only go into the lock it’s been designed to fit, and when you turn that key you open that lock – you activate that receptor, and that gives a signal into the cell. In the case of the IGF that signal is to grow, to develop, maybe to divide to produce more cells, and in particular not just to produce more cells but to be resistant to killing. And this is something that really characterises cancers. What they are very good at it is surviving - they are very good at not being killed. And IGFs is one of the factors that helps them to survive.

The normal process of cell death is called apoptosis, and this is very important because if you reduce the rate of apoptosis you will increase the likelihood of cancer. Because we are all of the time producing cancers in our bodies which never get anywhere because they just die, they have this pre-programmed death, the switch is thrown. But if you were to interrupt that system the cells would multiply very quickly – because that is the nature of a cancer. Now what is happening with high insulin levels and with high IGF-1 levels is that these two hormones reduce the rate at which this switch is thrown. So they permit or facilitate the growth of a cancer.

And there is a correlation between IGF1 levels and where you store your fat. The IGF1 levels are higher in people who are inappropriately storing fat in their liver, or in their muscle or in their gut cavity (apples rather than pears)
Re: IGF1 Measurement
04 Apr 2013, 18:11
A little bit later the female speaker went on about elevated insulin / insulin resistance and an analogy of loud music, then said at 15m25s

The person then becomes a type 2 diabetic, that has several consequences for cancer risk and the behaviour of cancers in cells , one is that it can increase the active amount of IGF in the blood. It doesn't actually change the amount of IGF in the blood but it reduces the levels of special binding proteins that stop the IGF being active all the time, so you've effectively got more active IGF in your blood if you have high insulin levels and you're Type 2 diabetic.

she then goes on to describe the effect of elevated blood sugar on cancer growth. After that is a description of insulin regulating fat storage.

Referring to Harvie's milky 5:2 calorie reduction study there was no significant reduction in Free or Total IGF-1 (bottom of table) however the two binding proteins IGF-BP1 & 2 did show significantly significant increases.

So perhaps we need to consider the whole IGF picture and not a single variable
Re: IGF1 Measurement
04 Apr 2013, 18:17
As I said, we need to look downstream of IGF-BP etc as there are other compounds that act at mTOR etc.
Re: IGF1 Measurement
04 Apr 2013, 21:15
Things may well be less straightforward than the original program suggested, in which case the value of having a measurement is presumably limited. Though the book did showcase MM's own IGF1 drop (28.6-15.9).
Re: IGF1 Measurement
05 Apr 2013, 07:55
PhilT wrote: Referring to Harvie's milky 5:2 calorie reduction study there was no significant reduction in Free or Total IGF-1 (bottom of table) however the two binding proteins IGF-BP1 & 2 did show significantly significant increases. So perhaps we need to consider the whole IGF picture and not a single variable

Thanks Phil for adding in that bit of the R4 programme, I hadn't meant to miss it out.

So does Free IGF-1 (aka Harvie) = Active IGF-1 (aka Macaulay)? And is this the important thing, not total IGF-1? And which one did Paul have measured? The figures in the Harvie study don't seem to compare to Paul's. And in the study the Free IGF-1 is a minute proportion of Total IGF-1. Confusing!

From the R4 programme I would have assumed that if Total IGF-1 stays the same and IGFBPs go up, then Free (or Active, assuming they are the same) IGF-1 would go down, because more IGF-1 would bind to the IGFBPs and not be free, but this isn't what happened in the Harvie study.

A study here (Copenhagen, 2006) on obese subjects found that a special 3 day VLCD reduced free IGF-1, raised ALS (acid labile subunit), left IGFBPs-1-3 proteolytic activity unchanged, and (unlike normal subjects) did not raise GH release. Not sure if that helps here or not, but the discussion section in the main paper has some interesting stuff about IGF-1 and IGFBPs and how they work together, which I couldn't quite get my head around but someone clever might fully understand. (Phil? Caroline? :wink: )
Re: IGF1 Measurement
05 Apr 2013, 08:44
Harvie's units are "IGF-1 Total (μg/L)" which is the same as ng/ml

A synopsis of the Horizon program reported that "Michael Morleys IGF level was 210ng/ml before the fast (could increase prostate cancer risk) (33m) (normal range for humans 80-230ng/ml). After 3.5 days fast MM IGF-1 level was 110 ng/ml" (Fontana) says
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

So what are the Medicheck units ? Their site is offline currently.
Re: IGF1 Measurement
05 Apr 2013, 08:48
They measure nmol/l (see their blog here) - they don't say whether their test is for total or active or free IGF-1, but maybe you can work it out for us?
Re: IGF1 Measurement
05 Apr 2013, 09:25
dominic wrote: They measure nmol/l (see their blog here) - they don't say whether their test is for total or active or free IGF-1, but maybe you can work it out for us?

Conversion factor 0.131 so Paul's 24.1 translates to 184 ng/ml

Has to be Total IGF-1 going by the magnitude.

Adults Male range, Mean, Female range, Mean
21 – 30 Years: 155 – 432 289 87 – 368 237
31 – 40 Years: 132 – 333 226 106 – 368 225
41 – 50 Years: 121 – 237 160 118 – 298 205
51 – 60 Years: 68 – 245 153 53 – 287 172
61 – 70 Years: 60 – 220 132 75 – 263 180
71 – 80 Years: 36 – 215 131 54 – 205 156

Restricting protein and intermittently reducing calories seems to be the way to get the lower values. The measurement is expensive and the "total" number may not be enough of the story, so my interest in IGF-1 is waning.......
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