Help Me Understand Free T

G_Chem

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I’m curious to know more about Free T compared to T which has binded with Albumin..

I read conflicting things, some say that T is binded and not easily available to the body whereas others say it dissociates easily from the Albumin.

I’ve been fighting cancer and went through chemo, I thought my T was bottomed out but after getting checked my Total T was in the high range of normal and my Free T pretty average.

That said I eat a very high protein diet and lots of nuts both of which is said to increase T binded with Albumin.

I’m kinda wondering if I should be dropping the nut intake since I eat a ton per day to increase my Free T count?

-GC
 
I know others will chime in and I'll try to add to mine here in a bit with more concrete information...

Albumin bound T may account for up to half, but it is a very weak chemical bond and thus can fluctuate. Majority of our T is bound up in SHBG (Sex Hormone Binding Globulin) that is produced by our livers. I'm not entirely sure of how one could change their diet to influence a lower level besides just upping protein and fat intake. SHBG tanks in the presence of AAS due to offsetting endogenous testosterone production.

From my own personal experience you really have to nag your PCP to get full hormone panels that include albumin/SHBG as well as estradiol assay or just pay out of pocket at private labs. I'm in the US though.

That said I eat a very high protein diet and lots of nuts both of which is said to increase T binded with Albumin.

I’m kinda wondering if I should be dropping the nut intake since I eat a ton per day to increase my Free T count?

First time I heard of it upon you mentioning that and I do see a few abstracts online relating to something along the lines of high polyunsaturated fat intake being linked to low bioavailable T. I'd have to read way more into it though and I can guarantee you someone other folks would know a lot more.

https://pubmed.ncbi.nlm.nih.gov/11525593/ One study utilized Japanese men in the age bracket of 43-88 so you have to take into account epigenetics and the general age bracket is hitting the nail on the head of men starting to veer into the lane of low T.
 
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One question: once T is attached to SHGB it get permanently lost or can it dettach and become free again?. If the latter is true, any way to trigger the detach?
 
One question: once T is attached to SHGB it get permanently lost or can it dettach and become free again?. If the latter is true, any way to trigger the detach?

I realize after @GrymReefer post this is another question I have. It seems nuts supposedly raise SHGB which I didn’t realize was different from Albumin bound T.

After having a read most common nuts are not good for T but Brazil, Macadamia and Tiger nuts are I guess.

I’ve begun a change to switch over to these nuts and will report back on my next bloodwork to see if my Free T number has risen or not.

-GC
 
One question: once T is attached to SHGB it get permanently lost or can it dettach and become free again?. If the latter is true, any way to trigger the detach?

Cortisol, estradiol, progesterone can all influence SHBG levels. Have to take into account the whole HPTA if you're trying to manipulate SHBG as it modulates androgens and estrogens. There is something called "Free Hormone Theory" in endocrinology that may help shed light on it. I'm not sure how one would heavily influence it without exogenous steroids/pharmacology or some strict diet protocols.
 
I'd be curious if any of the changes are statistically significant.
I know for total T going from like 400 to 500 isn't really anything to write home about.
 
I’m curious to know more about Free T compared to T which has binded with Albumin..

I read conflicting things, some say that T is binded and not easily available to the body whereas others say it dissociates easily from the Albumin.

I’ve been fighting cancer and went through chemo, I thought my T was bottomed out but after getting checked my Total T was in the high range of normal and my Free T pretty average.

That said I eat a very high protein diet and lots of nuts both of which is said to increase T binded with Albumin.

I’m kinda wondering if I should be dropping the nut intake since I eat a ton per day to increase my Free T count?

-GC

Here is an answer (to a similar question) Bill Roberts provided in a forum. I thought it was a good, concise explanation. You might find it interesting: "An exactly correct explanation is really not practical. The first part of being really correct, really has to be glossed over and presented by analogy.

A physical chemistry text or many analytical chemistry texts will present it rigorously, if interested. There is a concept and thing in physical chemistry called activity (which has very little to do with the ordinary meaning of the word) or chemical potential. It is in reference to energy of the system. When molecules are in solution and free to move, or free to move from the solid state into a liquid solution, they on average move in such a way as to yield equal chemical potential on both sides.

Kind of like how if you have two pools of water and run a hose between them, you may be sure that water will flow from the higher pool to the lower. And you may be sure that with time, assuming there's no issue of pools overflowing, they will, if water is free to flow from one to the other, that they will reach the same level.

Similarly, with solvents containing solutes (dissolved material), where the solutes are free to move from one solvent to the other, the chemical potential of the solutes in the solvents will equalize, and rapidly so if the solutes are reasonably free to exchange between the solvents.

A cruder but still fairly close way to look at this is "percent saturation" instead of chemical potential (the two are closely related.) If for example you have a container holding both chloroform and water (they don't mix) and some solute and you shake or stir them to give the solute the opportunity to move from one solvent to the other, if you find after this that the chloroform is say 50% saturated with the solute (that is, it could hold exactly twice as much before being unable to dissolve any more) then you would find that the water phase will also be almost exactly or maybe exactly 50% saturated.

Similarly if you have a solute -- say testosterone -- dissolved in the aqueous phase of the blood, that is, free in the water part of the blood, at some percentage of saturation, you would also find that 3 the fat in the body has testosterone dissolved in it at almost exactly or exactly the same percent saturation. Now, testosterone is probably at least 1000 times more soluble in fat than in water, so the concentration in the fat would be 1000 or more times higher, but not the percent saturation, which would be the same.

The same is true with regard to that which is bound by substances such as SHBG or serum albumin. They will be at the same percent of their saturation as the water is (or extremely close to it) but because their ability to solvate testosterone is vastly greater per milligram, the absolute quantity bound to such substances can be far beyond what is solvated free in the water.

So the reason free testosterone is a relatively small value while the amount bound to serum albumin is considerably higher, and the amount bound to SHBG is far higher, is because with testosterone being at the same chemical potential in each phase or substance (and it will be or extremely close to it at any time, as if it is not, it will rapidly move in such a manner as to equalize the chemical potential) the properties of serum albumin, SHBG, or for that matter fat, are such that the concentrations of testosterone in these or bound to these are far higher than what is the case in the aqueous phase of the blood.

In terms of evaluating the pharmacology of testosterone, or any other substance in the blood, every single equation for every single phenomenon related to receptor binding or rate of enzymatic conversion depends only on the free concentration.

The amounts sitting around in fat cells, or bound to SHBG, or serum albumin, aren't even in the equations. The chemical potential is what is relevant, and is fully known by the free testosterone figure.

Knowing how much T is bound to SHBG is no more important than knowing how much T is stored in fat cells or total in the body, for example.

That is to say, not important at all. (A fat person, for same free T, has far more testosterone stored in the body, by the way, but that fact does not result in more biological effect, though it likely has relevance to clearance of injected steroids.)

On knowing the free value, further information on total or "free and weakly bound" adds absolutely zero further useful knowledge. The exception is if one is interested in cellular signalling effects of SHBG itself, and one does know more about the amount of SHBG if knowing the amount of total testosterone after knowing the amount of free testosterone, as an indirect way of figuring amount of SHBG.

But the anabolic relevance is zero. Doctors, in general, do not understand this (or at least those that are not well versed in physical and/or analytical chemistry generally do not, and there are extremely few that are because they really don't need to know it) and there are countless examples in the medical literature, as well as other articles, that rely instead on what seems to be common sense. But what seems common sense just is completely off in this case."
 
“one does know more about the amount of SHBG if knowing the amount of total testosterone after knowing the amount of free testosterone, as an indirect way of figuring amount of SHBG”

I think this may answer my question. So if one has high total T but lower Free T it can be assumed much of that T is bound to SHBG?

It seems Almonds and Walnuts can raise SHBG 16-20% or so, which seems significant enough for me to reduce my intake.

-GC
 
“one does know more about the amount of SHBG if knowing the amount of total testosterone after knowing the amount of free testosterone, as an indirect way of figuring amount of SHBG”

I think this may answer my question. So if one has high total T but lower Free T it can be assumed much of that T is bound to SHBG?

It seems Almonds and Walnuts can raise SHBG 16-20% or so, which seems significant enough for me to reduce my intake.

-GC

There is evidence testosterone bound to SHBG triggers androgenic response via G-Protein coupled receptor action, so don't concern yourself too much..

Remember if not bound to SHBG testosterone is exposed to process of metabolic breakdown via CYP3A4, and other enzymes of metabolism..
 
There is evidence testosterone bound to SHBG triggers androgenic response via G-Protein coupled receptor action, so don't concern yourself too much..

Remember if not bound to SHBG testosterone is exposed to process of metabolic breakdown via CYP3A4, and other enzymes of metabolism..

Thank you for all the info man!

That first paragraph is pretty much my main concern so knowing it’s not much to worry about I’ll probably keep my diet the way it is. The cardiovascular health benefits from nuts is hard to walk away from... Last time I got my LDL/HDL checked the numbers were shockingly good.

I’m not really exhibiting signs of low T either besides being kinda hairless and not losing much of my head hair, but besides that all other signs point to healthy functioning. (I never had much body hair, one reason I thought my T was going to be low.)

I guess all things considered after everything I’ve been through lately I shouldn’t look a gift horse in the mouth, but if there was any way to further optimize my Free T number via diet or exercise I’d be open to it.

Thanks again guys :)

-GC
 
Some of us are just fortunate in keeping our hair lol. I've blasted the shit out of androgenic compounds and get 0 shedding. We picked our parents right for that I guess you could say lol.
 
Thank you for all the info man!

That first paragraph is pretty much my main concern so knowing it’s not much to worry about I’ll probably keep my diet the way it is. The cardiovascular health benefits from nuts is hard to walk away from... Last time I got my LDL/HDL checked the numbers were shockingly good.

I’m not really exhibiting signs of low T either besides being kinda hairless and not losing much of my head hair, but besides that all other signs point to healthy functioning. (I never had much body hair, one reason I thought my T was going to be low.)

I guess all things considered after everything I’ve been through lately I shouldn’t look a gift horse in the mouth, but if there was any way to further optimize my Free T number via diet or exercise I’d be open to it.

Thanks again guys :)

-GC

If you can, stay away from peanuts and cashews as they are seen as inflammatory, otherwise nuts are a great choice of healthy fats and protein..

If you wish to have optimally functioning LDL/HDL keep away from vegetable seed oils, processed grains and sugars/refined fructose, (anything that chronically elevates insulin, and blood triglycerides)..

Employ healthy diet and exercise, and your body should do the rest, don't stress about the small stuff..

If you unbind more testosterone from SHBG, if not binding androgen receptor, it will be metabolised... Which you don't want.. You could try 200ml of white grapefruit juice, as it is a known inhibitor of CYP3A4 (stops testosterone metabolism, leaving more in blood to trigger effect)...
 
Grapefruit juice works wonders. Of course be sure no medications you're taking are contraindicated with it such as antidepressants, etc
 
I would like the effect without all the sugars. It is know what component of the grapefruit inhibits the enzyme? Does grapefruit extract exist/work or similar?
 
I would like the effect without all the sugars. It is know what component of the grapefruit inhibits the enzyme? Does grapefruit extract exist/work or similar?
It is the flavanoids in the grapefruit itself. Idk if there's an extract or anything like that as there isn't really much of a market for it as most people are trying to avoid the build up of chemicals in their body, not promote it.
 
I would like the effect without all the sugars. It is know what component of the grapefruit inhibits the enzyme? Does grapefruit extract exist/work or similar?

Content of CYP3A4 inhibitors, naringin, naringenin and bergapten in grapefruit and grapefruit juice products


You could try grapefruit itself, not juiced, whilst bound to fiber the fructose content isn't as much of a problem..
 

Content of CYP3A4 inhibitors, naringin, naringenin and bergapten in grapefruit and grapefruit juice products


You could try grapefruit itself, not juiced, whilst bound to fiber the fructose content isn't as much of a problem..
Super interesting. Thanks!
 
If you can, stay away from peanuts and cashews as they are seen as inflammatory, otherwise nuts are a great choice of healthy fats and protein..

If you wish to have optimally functioning LDL/HDL keep away from vegetable seed oils, processed grains and sugars/refined fructose, (anything that chronically elevates insulin, and blood triglycerides)..

Employ healthy diet and exercise, and your body should do the rest, don't stress about the small stuff..

If you unbind more testosterone from SHBG, if not binding androgen receptor, it will be metabolised... Which you don't want.. You could try 200ml of white grapefruit juice, as it is a known inhibitor of CYP3A4 (stops testosterone metabolism, leaving more in blood to trigger effect)...

Yup I try to avoid peanuts for a variety reasons (alfatoxins can mess up gut biome too), although didn’t know that about cashews. I eat mainly hazelnuts and pistachios, with some peanut and almond too. (Peanuts taste damn good.)

Stopped most sugars long ago, I try to keep to one piece of fruit later at night. Only water, no juices even. Really got my final step off processed carbs after my recent Whole30 run.

I’ll definitely keep in mind on the grapefruit juice though, I eat grapefruits every now and again. But I hear the white grapefruit juice is different.


One final question, I think, but say I start drinking grapefruit juice daily to try and hold back Free T metabolism, is there some sort of feedback loop that will make my body slow T production down in any way? Just curious.

-GC
 
Yup I try to avoid peanuts for a variety reasons (alfatoxins can mess up gut biome too), although didn’t know that about cashews. I eat mainly hazelnuts and pistachios, with some peanut and almond too. (Peanuts taste damn good.)

Stopped most sugars long ago, I try to keep to one piece of fruit later at night. Only water, no juices even. Really got my final step off processed carbs after my recent Whole30 run.

I’ll definitely keep in mind on the grapefruit juice though, I eat grapefruits every now and again. But I hear the white grapefruit juice is different.


One final question, I think, but say I start drinking grapefruit juice daily to try and hold back Free T metabolism, is there some sort of feedback loop that will make my body slow T production down in any way? Just curious.

-GC

I'm not too sure, although you might think too much enzymatic inhibition might trigger increased production..

Due to the fructose spike from juice, maybe consider the grapefruit itself, whilst bound to fiber the transition of fructose is slowed so doesn't impact insulin as much..
 
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