Free Radicals

[optimus prime]

I have been doing some reading and there seems to be a lot of talk about free radicals, and their role in causing damage to cells.

So here is a theory in simple terms (very simple terms). Let me know what you think.

My theory

Free radicals can damage follicle cells allowing them to become sensitive to DHT. As you get older you produce less DHT but have more free radicals - thus making the follicles more sensitive to DHT. It could be that the free radicals prevent the hair follicle cells from repairing themselves against the DHT.

* This might explain why we still lose hair as we get older but have less DHT.

This would also explain why finasteride and dutasteride gradually stop working over time, because the damage the free radicals are doing is making the follicles more and more sensitive.

Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons and can be formed when oxygen interacts with certain molecules. Once formed, these highly reactive radicals can start a chain reaction, like dominoes. It is believed that their chief danger comes from the damage they can do when they react with important cellular components such as DNA, or the cell membrane. Cells may function poorly or die if this occurs.
http://www.baldingblog.com/2006/02/10/b ... hair-loss/

So what about sports stars that are really healthy. Well according to the quote below, the body creates superoxide dismutase (SOD) to 'reign' in the free radicals, but what if some humans (even young) are genetically not able to create enough superoxide dismutase to deal with the number of free radicals?

You will get male pattern baldness no matter how healthy you think you are. Also the western diet can increase the number of free radicals.

When we're young, our cells have a defense system known as superoxide dismutase (SOD) that reins in those free radicals, but as we get older, SOD doesn't work as well. That leaves the free radicals to have their way with our cells, and when the damage gets to be too much, the cells die and so do we.
http://health.howstuffworks.com/wellnes ... -aging.htm

It would also explain why treatments like Copper Peptides work well alongside finasteride & dutasteride.

COPPER PEPTIDES are the main active ingredient in Tricomin and Folligen. Copper peptides improve the skin's antioxidant defences by activating superoxide dismutase (SOD), a protein which detoxifies free radicals and is the body's primary antioxidant defence.

 

[optimus prime]

Some people will say, why hair follicles in the male pattern baldness area, why not the sides and body hair.

Well this has not been answered yet, the only answer people have is genetics, and my theory makes no difference to that.

My theory is to address why some people have male pattern baldness and some don't. It could be that either or all of the below:

1. I have more free radical because I eat a diet that causes them.
2. I eat a diet that does not fight free radicals (low in antioxidants)
3. Genetics and my body does not create as many SOD to 'reign in' the free radicals.

This may also explain why men who are bald are more likely to get prostate cancer. The free radicals allow the DHT to damage the prostate.

 

[Bryan]

My theory

Free radicals can damage follicle cells allowing them to become sensitive to DHT. As you get older you produce less DHT but have more free radicals - thus making the follicles more sensitive to DHT. It could be that the free radicals prevent the hair follicle cells from repairing themselves against the DHT.

But why do hair follicles have opposite responses to androgens (the growth of beard and other body hair is STIMULATED by them, while the growth of scalp hair is SUPPRESSED by them)? :dunno:

 

[powersam]

My theory

Free radicals can damage follicle cells allowing them to become sensitive to DHT. As you get older you produce less DHT but have more free radicals - thus making the follicles more sensitive to DHT. It could be that the free radicals prevent the hair follicle cells from repairing themselves against the DHT.

But why do hair follicles have opposite responses to androgens (the growth of beard and other body hair is STIMULATED by them, while the growth of scalp hair is SUPPRESSED by them)? :dunno:

Didn't you say that an experiment had been run where follicles were implanted from the balding part of the head to an arm, and continued to miniaturise?


Optimus - Do you have a link to something showing that your gets DHT lower as you get older? I've read in other places that it gets higher as more is converted from normal T to make up for dropping T levels. DHT being a more potent version of T.

 

[Bryan]

Didn't you say that an experiment had been run where follicles were implanted from the balding part of the head to an arm, and continued to miniaturise?

Yes. That's the Nordstrom experiment.

Optimus - Do you have a link to something showing that your gets DHT lower as you get older? I've read in other places that it gets higher as more is converted from normal T to make up for dropping T levels. DHT being a more potent version of T.

I've never heard of any way that the conversion of testosterone into DHT is controlled or regulated by any kind of feedback loop. I think that's just a function of available testosterone, 5a-reductase, and NADPH.

It's the production of testosterone which is closely controlled and regulated by the brain; I believe that's why testosterone is upregulated a bit when you take finasteride/dutasteride.

 

[powersam]

This study suggests (if I read it correctly) that some sort of feedback mechanism is in play:

http://www.ncbi.nlm.nih.gov/pubmed/18811920

The study revealed that in a cohort of elderly men with subnormal plasma T levels plasma DHT levels declined upon T administration when they were in the higher range of normal (>0.6 nmol l(-1)), with a profound shift of DHT/T ratios presumed to be an indicator of a reduced 5alpha-reductase activity. Below plasma DHT levels of 0.6 nmol l(-1), responses of plasma DHT to T administration varied.

 

[Bryan]

Yeah, that study has been mentioned here more than once in the past. I really can't think of any way to explain it, other than hypothesizing some heretofore unmentioned and undescribed "feedback loop". I'm a bit suspicious of their trial, though. I'd like to see it duplicated by some other group! I'd also like to know just how big the "cohort" was, in which they supposedly found that effect.

 

[optimus prime]

But why do hair follicles have opposite responses to androgens (the growth of beard and other body hair is STIMULATED by them, while the growth of scalp hair is SUPPRESSED by them)? :dunno:

Well my theory does not address this. My theory is mainly aimed at addressing why one person gets male pattern baldness and one does not.

So the reason why some follicles have opposite responses to androgens is same as your theory, which I believe is genetics. Same reason arm hairs don't grow really long, or beard hair is different texture to head hair.

 

[optimus prime]

Optimus - Do you have a link to something showing that your gets DHT lower as you get older? I've read in other places that it gets higher as more is converted from normal T to make up for dropping T levels. DHT being a more potent version of T.

Hi Powersam,

I believe it was Bryan in another thread long ago that said DHT is lower in older men. I have also heard it before from other people. Here is a link and quote:

Unless I am mistaken, DHT levels will correspond with testosterone levels. Generally, less testosterone (an aging problem) should produce less DHT.
http://www.baldingblog.com/2007/07/06/d ... -they-age/

 

[Bryan]

But why do hair follicles have opposite responses to androgens (the growth of beard and other body hair is STIMULATED by them, while the growth of scalp hair is SUPPRESSED by them)? :dunno:

Well my theory does not address this. My theory is mainly aimed at addressing why one person gets male pattern baldness and one does not.

So the reason why some follicles have opposite responses to androgens is same as your theory, which I believe is genetics. Same reason arm hairs don't grow really long, or beard hair is different texture to head hair.

For a long time my theory has been that an important reason why one person gets male pattern baldness and another does not is that difference in response that we're talking about. In my opinion, it's not just the usual answer that everybody usually repeats over and over ("A balding person has higher levels of DHT and androgen receptors"), I think another major factor is that a balding person has a more intense response to androgens by his scalp hair follicles: a given amount of androgens causes his follicles to release a greater quantity of growth-suppressive chemicals than the follicles of a non-balding person, even if all other things are equal.

 

[optimus prime]

For a long time my theory has been that an important reason why one person gets male pattern baldness and another does not is that difference in response that we're talking about. In my opinion, it's not just the usual answer that everybody usually repeats over and over ("A balding person has higher levels of DHT and androgen receptors"), I think another major factor is that a balding person has a more intense response to androgens by his scalp hair follicles: a given amount of androgens causes his follicles to release a greater quantity of growth-suppressive chemicals than the follicles of a non-balding person, even if all other things are equal.

I agree 100% with this. I think I have the same amount of DHT as my brothers, same number of receptors as them. We have the same diet. But I have male pattern baldness, they don't.

So I wonder, why does my hair follicle release this growth suppressive chemical, and why does it produce more as time goes on?

Could it be the free radicals are damaging the cell DNA to make it produce this chemical when DHT binds with receptors?

Could it be that I produce less SOD than my brothers to remove free radicals?

 

[Bryan]

Do you remember a study where the researchers took a hair from the donor section of the scalp and exposed it to a high level of androgen (DHT I believe, and a really, really high level) and it began to miniturize. Seems like I remember you posting a reply to that and Armando was responding to it as well?

Yes. There's a study which has been cited here a few times that showed that even non-balding hair follicles from the "donor" areas are sensitive to androgens, but much less so than other scalp hair follicles. Even "donor" follicles apparently will miniaturize, if you pump them full of enough androgens!

 

[powersam]

Yeah, that study has been mentioned here more than once in the past. I really can't think of any way to explain it, other than hypothesizing some heretofore unmentioned and undescribed "feedback loop". I'm a bit suspicious of their trial, though. I'd like to see it duplicated by some other group! I'd also like to know just how big the "cohort" was, in which they supposedly found that effect.

I don't think you can just sweep it away like that, the methodology was good. Asking to see others repeat the results invalidates a hell of a lot of research, like Kligmans sebum research for example.

 

[powersam]

Optimus - Do you have a link to something showing that your gets DHT lower as you get older? I've read in other places that it gets higher as more is converted from normal T to make up for dropping T levels. DHT being a more potent version of T.

Hi Powersam,

I believe it was Bryan in another thread long ago that said DHT is lower in older men. I have also heard it before from other people. Here is a link and quote:

Unless I am mistaken, DHT levels will correspond with testosterone levels. Generally, less testosterone (an aging problem) should produce less DHT.
http://www.baldingblog.com/2007/07/06/d ... -they-age/

Lower compared to what though? Lower as a percentage of testosterone or lower compared to younger men?

http://www.ncbi.nlm.nih.gov/pubmed/20534765 This one says they're all pretty much the same, which does not at all discount the idea that DHT rises to make up for low test.

The feedback idea seems backed up by this study http://jcem.endojournals.org/cgi/conten ... /9/4078#F1 which shows external administrations of DHT lowering testosterone.

 

[Bryan]

Thanks for remembering...I can't find the study for noth'n (much appreciated if you have it handy to post it)..

Sorry, I don't have it handy, either. I simply read the abstract after somebody posted it in the past, but didn't save it.

..so, in your theory, the "response" is genetic?

Yes. I think that's likely.

Seems to me....that all scalp hair will miniturize in response to too much androgen?

Seems like it, although their tendency to do that can vary ENORMOUSLY from one follicle to another.

Sounds more like a reaction than a response? :dunno:

I'm not sure what you mean. Please explain.

 

[Bryan]

I don't think you can just sweep it away like that, the methodology was good. Asking to see others repeat the results invalidates a hell of a lot of research...

LOL! I doubt it! What was the size of the "cohort" which showed that effect? Was it only two or three men? If it was a fairly small group, I'd like to see it duplicated by other researchers before I can fully accept those experimental results. As I said before, I have never EVER seen or heard of any other evidence suggesting a "feedback loop" for the production of DHT. It's going to take more than just a small "cohort" of men within a larger test to make me believe in one.

...like Kligmans sebum research for example.

Kligman did a lot of research on sebum. Do you have something specific in mind?

 

[Bryan]

http://www.ncbi.nlm.nih.gov/pubmed/20534765 This one says they're all pretty much the same, which does not at all discount the idea that DHT rises to make up for low test.

I've cited French studies in the past showing that DHT levels are reduced in older men. The study above doesn't "discount" the idea that DHT rises to make up for low testosterone, but it certainly doesn't support it, either!

The feedback idea seems backed up by this study http://jcem.endojournals.org/cgi/conten ... /9/4078#F1 which shows external administrations of DHT lowering testosterone.

Huh?? Nobody denies that giving DHT externally will suppress the synthesis of testosterone. That's just the HPT axis at work! The question is whether or not giving testosterone will reduce the formation of DHT, which is the opposite of that. That's something I won't believe until I see some more scientific support for it, besides that other odd study you cited recently.

 

[armandein]

But why do hair follicles have opposite responses to androgens (the growth of beard and other body hair is STIMULATED by them, while the growth of scalp hair is SUPPRESSED by them)? :dunno:

Well my theory does not address this. My theory is mainly aimed at addressing why one person gets male pattern baldness and one does not.

So the reason why some follicles have opposite responses to androgens is same as your theory, which I believe is genetics. Same reason arm hairs don't grow really long, or beard hair is different texture to head hair.

For a long time my theory has been that an important reason why one person gets male pattern baldness and another does not is that difference in response that we're talking about. In my opinion, it's not just the usual answer that everybody usually repeats over and over ("A balding person has higher levels of DHT and androgen receptors"), I think another major factor is that a balding person has a more intense response to androgens by his scalp hair follicles: a given amount of androgens causes his follicles to release a greater quantity of growth-suppressive chemicals than the follicles of a non-balding person, even if all other things are equal.

A picture is worth a thousand words

 

[powersam]

Must admit I missed the cohort bit, a old research buddy is going to grab me the full pdf next week.

 

[optimus prime]

Lower compared to what though? Lower as a percentage of testosterone or lower compared to younger men?

http://www.ncbi.nlm.nih.gov/pubmed/20534765 This one says they're all pretty much the same, which does not at all discount the idea that DHT rises to make up for low test.

The feedback idea seems backed up by this study http://jcem.endojournals.org/cgi/conten ... /9/4078#F1 which shows external administrations of DHT lowering testosterone.

I'll be honest I don't know. It is worth discussing this though. Although I don't think it makes a huge difference to the free radical theory.