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Thread: KPRF, LRP-1 and Metalloproteinases

  1. #1
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    Default KPRF, LRP-1 and Metalloproteinases

    Hello everyone! This will be my first post, and possibly a very lengthy one. I guess a short introduction is in order: I'm a 23 year old male, suffering from what seems to be a typical case of KPRF. I've had this condition since childhood, but since puberty it has gotten progressively worse, and since I turned 19 it has been really bad. Now I don't need to explain to all of you how these conditions affect a person, so I won't, but let's just say my life has been very much affected, with social anxiety, avoidant behaviour and depression. It has also made me very keen on finding something as close to a cure as I possibly can. Please note though, that I'm not a biologist or anything of that sort, so I apologise in advance if any of this is wrong.

    I've noticed that there is not much talk about KPRF around here, and certainly not from a "sciency" perspective, which I guess is really only due to the fact that there is almost no research into KP and related disorders. However, a while ago there was a research paper published which piqued my interest: Whole exome sequencing identifies LRP-1 as a pathogenic gene in autosomal recessive keratosis pilaris atrophicans. The gist of it is that KPAF seems to be linked to a faulty version of the gene LRP-1 (low density lipoprotein related receptor 1), which encodes the LRP-1 receptor, which is abundant in many tissues. In the words of the paper authors, "The LRP1 mRNA and LRP1 protein levels in fibroblasts of affected individuals were markedly reduced when compared with controls. Similarly, the LRP1-mediated cellular uptake of α(2)M was reduced in patient fibroblasts."

    Before I continue, I must say that I have no hard evidence to suggest that LRP-1 is involved in KPRF. And until there are studies done (if ever), I wont. However, from an empirical view, the pathogenesis of the different KP variants are similiar. Another point to be made, although vauge, is that KP/KPRF/KPAF is reported to somewhat come and go with age (increasing in puberty, slowly improving as one get older). This to me seems affected by hormones, as they increase in puberty and lowers as time goes by. The expression of LRP-1 has been shown to be affected by androgens, which could explain this pattern (although many processes are affected by hormones, so this is not definitive). Expression of LRP-1 has also been shown to increase with age in rats (or perhaps mice, I cant remember at the moment). And as a personal anecdote, my grandfather, from whom me and my mother and sisters inherited the KP issues, passed away from a ruptured stomach aorta, which has been linked to LRP-1 mutations. So as I said, I have no hard evidence that this is the same for KPRF, and maybe I'm grasping for straws here. Perhaps (probably) LRP-1 is not the single root cause of keratinization disorders, but it could be a major factor.

    LRP-1 has many functions, and interact with many things, much of which I am to dumb to understand. There could be any number of reasons why LRP-1 would affect KPRF. One thing in particular stands out to me though. LRP-1, among other things, acts as a regulator of metalloproteinases, and of particular interest metalloproteinase-9 (MMP-9), and possibly MMP-2. These MMPs are involved in inflammation, angiogenesis, the structural integrity of extracellular matrix, cancer development etc. They have also been linked as a problem in general rosacea before. Though I cant back this up, it could be that lower levels of LRP-1 would increase levels of MMPs.

    I should stop rambling now, but hopefully this can spur some more people to look into this theory of LRP-1 and possibly MMPs. I will list some theoretical ways of treatment below. I have not been able to experiment much though, as I am a poor university student at the moment. I should also add sources for my claims, I will return to this when it's not in the middle of the night.

    Treatment by upregulating LRP-1 (this would be the ideal option imo):
    Havent found much on the web for this, but here goes.
    • Withania Somnifera extract (also known as Ashwangandha). Has been shown to upregulate LRP-1 in mice, with extreme doses, in an alzheimers study. Might be beneficial.
    • Oleocanthal. Found in olive oil, currently no extract available.
    • Resveratrol. (Maybe, not sure).


    Treatment by inhibiting MMP-9 and MMP-2 (not the ideal option but might be easier):
    If my theory is correct, inhibition of MMPs should both reduce redness in the short term by being antiinflammatory, but also improve the condition as time goes by.
    • EGCG-Green Tea Extract. Generally antiinflammatory, and inhibits MMP-9 and MMP-2.
    • ALA-Inhibits MMP-9.
    • Vitamin C. (Has also been shown to inhibit MMPs topically. The most effective form in this regard seems to be tetrahexyldecyl ascorbate).
    • Evening primrose oil - Generally antiinflammatory, and it's polyphenols have been shown to inhibit MMP-9.
    • Curcumin-Generally antiinflammatory, may inhibit MMP-9.
    • Quercetin.
    • Luteolin.
    • If gluten intolerant-stop eating gluten. A study has shown that people sensitive to gluten have higher levels of MMP-9.
    • I've forgot a few items, will add some more later.


    Of the above, I've tried so far EGCG, and EPO. EGCG had a great effect, at least more effective than any other supplement ive taken before. It decreased redness quite fast, and made my face mych calmer. When taken every day for a while, it also seemed to make my skin much smoother, and less red and reactive even on the odd day that I didn't take it. When taking EGCG, it's important to take it on an empty stomach, atleast 4 hours since the last meal. Otherwise, bioavailability is very low. Brand also seems to make a difference. At first I used the NOW brand, which worked good. When I ran out, I bought a higher dose brand called Peak, which does not seem to work nearly as well. Also don't overdose, as it can be hepatoxic at very high doses. I used 6-800 mg per day, split into 2 doses. I had the same experience with EPO, although not as powerful as EGCG. Curiously, brand also made a difference here. Don't remember which one worked though.

    Wow, that was a lot of text! Hope it's not to incoherent, and that this is useful to someone

  2. #2
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    Hi do you have any befor and after pictures from taking the green tea extract.
    Thanks

  3. #3
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    Very interesting, I commend you on all of your hard work and research, determined KPRF sufferers like ourselves are crucial in identifying effective treatments and possibly even cures.!

    As stated above, I also have KPRF, luckily it isn't an extreme case, but the flushing and redness is still quite bothersome. I have experimented with dozens of topical products with little to no success unfortunately. I actually tried topical Vitamin C for a couple months, it helped slightly with baseline redness but did nothing for flushing. I've decided to opt for laser treatment since it seems to be the only proven successful method for controlling flushing and reversing baseline redness.

    Interesting you mention Evening Primrose Oil though, because I remember a couple years back on the old Keratosis Pilaris forum that someone started a thread claiming that EPO almost completely cleared their KPRF. I was skeptical about the whole thing but I remember they were quite adamant that the EPO was succesful. Unfortunately that forum is no longer accessible, which sucks because there is probably some really useful information on there!

    I'll definitely check put the EGCG though, that could be quite beneficial to combine with my laser treatments.

    Good luck! And please keep us posted

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    Quote Originally Posted by ketokprf View Post
    Hello everyone! This will be my first post, and possibly a very lengthy one. I guess a short introduction is in order: I'm a 23 year old male, suffering from what seems to be a typical case of KPRF. I've had this condition since childhood, but since puberty it has gotten progressively worse, and since I turned 19 it has been really bad. Now I don't need to explain to all of you how these conditions affect a person, so I won't, but let's just say my life has been very much affected, with social anxiety, avoidant behaviour and depression. It has also made me very keen on finding something as close to a cure as I possibly can. Please note though, that I'm not a biologist or anything of that sort, so I apologise in advance if any of this is wrong.

    I've noticed that there is not much talk about KPRF around here, and certainly not from a "sciency" perspective, which I guess is really only due to the fact that there is almost no research into KP and related disorders. However, a while ago there was a research paper published which piqued my interest: Whole exome sequencing identifies LRP-1 as a pathogenic gene in autosomal recessive keratosis pilaris atrophicans. The gist of it is that KPAF seems to be linked to a faulty version of the gene LRP-1 (low density lipoprotein related receptor 1), which encodes the LRP-1 receptor, which is abundant in many tissues. In the words of the paper authors, "The LRP1 mRNA and LRP1 protein levels in fibroblasts of affected individuals were markedly reduced when compared with controls. Similarly, the LRP1-mediated cellular uptake of α(2)M was reduced in patient fibroblasts."

    Before I continue, I must say that I have no hard evidence to suggest that LRP-1 is involved in KPRF. And until there are studies done (if ever), I wont. However, from an empirical view, the pathogenesis of the different KP variants are similiar. Another point to be made, although vauge, is that KP/KPRF/KPAF is reported to somewhat come and go with age (increasing in puberty, slowly improving as one get older). This to me seems affected by hormones, as they increase in puberty and lowers as time goes by. The expression of LRP-1 has been shown to be affected by androgens, which could explain this pattern (although many processes are affected by hormones, so this is not definitive). Expression of LRP-1 has also been shown to increase with age in rats (or perhaps mice, I cant remember at the moment). And as a personal anecdote, my grandfather, from whom me and my mother and sisters inherited the KP issues, passed away from a ruptured stomach aorta, which has been linked to LRP-1 mutations. So as I said, I have no hard evidence that this is the same for KPRF, and maybe I'm grasping for straws here. Perhaps (probably) LRP-1 is not the single root cause of keratinization disorders, but it could be a major factor.

    LRP-1 has many functions, and interact with many things, much of which I am to dumb to understand. There could be any number of reasons why LRP-1 would affect KPRF. One thing in particular stands out to me though. LRP-1, among other things, acts as a regulator of metalloproteinases, and of particular interest metalloproteinase-9 (MMP-9), and possibly MMP-2. These MMPs are involved in inflammation, angiogenesis, the structural integrity of extracellular matrix, cancer development etc. They have also been linked as a problem in general rosacea before. Though I cant back this up, it could be that lower levels of LRP-1 would increase levels of MMPs.

    I should stop rambling now, but hopefully this can spur some more people to look into this theory of LRP-1 and possibly MMPs. I will list some theoretical ways of treatment below. I have not been able to experiment much though, as I am a poor university student at the moment. I should also add sources for my claims, I will return to this when it's not in the middle of the night.

    Treatment by upregulating LRP-1 (this would be the ideal option imo):
    Havent found much on the web for this, but here goes.
    • Withania Somnifera extract (also known as Ashwangandha). Has been shown to upregulate LRP-1 in mice, with extreme doses, in an alzheimers study. Might be beneficial.
    • Oleocanthal. Found in olive oil, currently no extract available.
    • Resveratrol. (Maybe, not sure).


    Treatment by inhibiting MMP-9 and MMP-2 (not the ideal option but might be easier):
    If my theory is correct, inhibition of MMPs should both reduce redness in the short term by being antiinflammatory, but also improve the condition as time goes by.
    • EGCG-Green Tea Extract. Generally antiinflammatory, and inhibits MMP-9 and MMP-2.
    • ALA-Inhibits MMP-9.
    • Vitamin C. (Has also been shown to inhibit MMPs topically. The most effective form in this regard seems to be tetrahexyldecyl ascorbate).
    • Evening primrose oil - Generally antiinflammatory, and it's polyphenols have been shown to inhibit MMP-9.
    • Curcumin-Generally antiinflammatory, may inhibit MMP-9.
    • Quercetin.
    • Luteolin.
    • If gluten intolerant-stop eating gluten. A study has shown that people sensitive to gluten have higher levels of MMP-9.
    • I've forgot a few items, will add some more later.


    Of the above, I've tried so far EGCG, and EPO. EGCG had a great effect, at least more effective than any other supplement ive taken before. It decreased redness quite fast, and made my face mych calmer. When taken every day for a while, it also seemed to make my skin much smoother, and less red and reactive even on the odd day that I didn't take it. When taking EGCG, it's important to take it on an empty stomach, atleast 4 hours since the last meal. Otherwise, bioavailability is very low. Brand also seems to make a difference. At first I used the NOW brand, which worked good. When I ran out, I bought a higher dose brand called Peak, which does not seem to work nearly as well. Also don't overdose, as it can be hepatoxic at very high doses. I used 6-800 mg per day, split into 2 doses. I had the same experience with EPO, although not as powerful as EGCG. Curiously, brand also made a difference here. Don't remember which one worked though.

    Wow, that was a lot of text! Hope it's not to incoherent, and that this is useful to someone

    Excellent post. Fellow KPRF sufferer.

    Funnily enough I thought I found improvement with EGCG a while ago, however ultimately I was unsure whether it really made an improvement. I started drinking green tea, randomly noticed an improvement in redness, then made a connection when I found some research articles linking to EGCG to improved keratin regulation. It was so long ago I can't remember the exact article, but something along these lines: http://www.sciencedaily.com/releases...0425071800.htm

    Please keep us updated with your research.

    realwork

  5. #5
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    Quote Originally Posted by ketokprf View Post
    Hello everyone! This will be my first post, and possibly a very lengthy one. I guess a short introduction is in order: I'm a 23 year old male, suffering from what seems to be a typical case of KPRF. I've had this condition since childhood, but since puberty it has gotten progressively worse, and since I turned 19 it has been really bad. Now I don't need to explain to all of you how these conditions affect a person, so I won't, but let's just say my life has been very much affected, with social anxiety, avoidant behaviour and depression. It has also made me very keen on finding something as close to a cure as I possibly can. Please note though, that I'm not a biologist or anything of that sort, so I apologise in advance if any of this is wrong.

    I've noticed that there is not much talk about KPRF around here, and certainly not from a "sciency" perspective, which I guess is really only due to the fact that there is almost no research into KP and related disorders. However, a while ago there was a research paper published which piqued my interest: Whole exome sequencing identifies LRP-1 as a pathogenic gene in autosomal recessive keratosis pilaris atrophicans. The gist of it is that KPAF seems to be linked to a faulty version of the gene LRP-1 (low density lipoprotein related receptor 1), which encodes the LRP-1 receptor, which is abundant in many tissues. In the words of the paper authors, "The LRP1 mRNA and LRP1 protein levels in fibroblasts of affected individuals were markedly reduced when compared with controls. Similarly, the LRP1-mediated cellular uptake of α(2)M was reduced in patient fibroblasts."

    Before I continue, I must say that I have no hard evidence to suggest that LRP-1 is involved in KPRF. And until there are studies done (if ever), I wont. However, from an empirical view, the pathogenesis of the different KP variants are similiar. Another point to be made, although vauge, is that KP/KPRF/KPAF is reported to somewhat come and go with age (increasing in puberty, slowly improving as one get older). This to me seems affected by hormones, as they increase in puberty and lowers as time goes by. The expression of LRP-1 has been shown to be affected by androgens, which could explain this pattern (although many processes are affected by hormones, so this is not definitive). Expression of LRP-1 has also been shown to increase with age in rats (or perhaps mice, I cant remember at the moment). And as a personal anecdote, my grandfather, from whom me and my mother and sisters inherited the KP issues, passed away from a ruptured stomach aorta, which has been linked to LRP-1 mutations. So as I said, I have no hard evidence that this is the same for KPRF, and maybe I'm grasping for straws here. Perhaps (probably) LRP-1 is not the single root cause of keratinization disorders, but it could be a major factor.

    LRP-1 has many functions, and interact with many things, much of which I am to dumb to understand. There could be any number of reasons why LRP-1 would affect KPRF. One thing in particular stands out to me though. LRP-1, among other things, acts as a regulator of metalloproteinases, and of particular interest metalloproteinase-9 (MMP-9), and possibly MMP-2. These MMPs are involved in inflammation, angiogenesis, the structural integrity of extracellular matrix, cancer development etc. They have also been linked as a problem in general rosacea before. Though I cant back this up, it could be that lower levels of LRP-1 would increase levels of MMPs.

    I should stop rambling now, but hopefully this can spur some more people to look into this theory of LRP-1 and possibly MMPs. I will list some theoretical ways of treatment below. I have not been able to experiment much though, as I am a poor university student at the moment. I should also add sources for my claims, I will return to this when it's not in the middle of the night.

    Treatment by upregulating LRP-1 (this would be the ideal option imo):
    Havent found much on the web for this, but here goes.
    • Withania Somnifera extract (also known as Ashwangandha). Has been shown to upregulate LRP-1 in mice, with extreme doses, in an alzheimers study. Might be beneficial.
    • Oleocanthal. Found in olive oil, currently no extract available.
    • Resveratrol. (Maybe, not sure).


    Treatment by inhibiting MMP-9 and MMP-2 (not the ideal option but might be easier):
    If my theory is correct, inhibition of MMPs should both reduce redness in the short term by being antiinflammatory, but also improve the condition as time goes by.
    • EGCG-Green Tea Extract. Generally antiinflammatory, and inhibits MMP-9 and MMP-2.
    • ALA-Inhibits MMP-9.
    • Vitamin C. (Has also been shown to inhibit MMPs topically. The most effective form in this regard seems to be tetrahexyldecyl ascorbate).
    • Evening primrose oil - Generally antiinflammatory, and it's polyphenols have been shown to inhibit MMP-9.
    • Curcumin-Generally antiinflammatory, may inhibit MMP-9.
    • Quercetin.
    • Luteolin.
    • If gluten intolerant-stop eating gluten. A study has shown that people sensitive to gluten have higher levels of MMP-9.
    • I've forgot a few items, will add some more later.


    Of the above, I've tried so far EGCG, and EPO. EGCG had a great effect, at least more effective than any other supplement ive taken before. It decreased redness quite fast, and made my face mych calmer. When taken every day for a while, it also seemed to make my skin much smoother, and less red and reactive even on the odd day that I didn't take it. When taking EGCG, it's important to take it on an empty stomach, atleast 4 hours since the last meal. Otherwise, bioavailability is very low. Brand also seems to make a difference. At first I used the NOW brand, which worked good. When I ran out, I bought a higher dose brand called Peak, which does not seem to work nearly as well. Also don't overdose, as it can be hepatoxic at very high doses. I used 6-800 mg per day, split into 2 doses. I had the same experience with EPO, although not as powerful as EGCG. Curiously, brand also made a difference here. Don't remember which one worked though.

    Wow, that was a lot of text! Hope it's not to incoherent, and that this is useful to someone
    Very interesting. I am taking quite a few of the supplements you recommend but I have rosacea, not KPRF. I did take the EGCG but I do not remember keeping it away from food-- was not aware of the bioavailability issue. Do you have a reference for that as I would like to show my doctor? And do you think it is the same with drinking the tea? I often drink green tea in the morning (though right now I am on a coffee kick) but the problem for me is that my stomach got sensitive to it and I have to be careful not to let it get too strong or it nauseates me. Have you experimented with the green tea extract topically? My sunscreen has it in it (also zinc) and I find it very calming to the skin; sometimes I use it even when I don't plan to go out in the sun just to soothe my skin if it feels aggravated.

  6. #6
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    any updates on your research buddy?

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    very interesting.. I wonder why there's no research in this topic :/

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    Ashwangandha extract doesn't seem very expensive, we have to research more ;)

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    Quote Originally Posted by darkside View Post
    Ashwangandha extract doesn't seem very expensive, we have to research more ;)
    Agreed. Even though I have got my KPRF mostly under control, I am going to order this and see what happens and report back:

    http://healthtonics.co.uk/home/35-as...469492694.html

  10. #10
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    Scratch that link, apparently it needs to be root only.

    http://www.amazon.co.uk/Swanson-Ashw...dp/B002MT8R70/

    The first review, very interesting:

    Captu44re.JPG
    Last edited by realwork; 16th February 2016 at 02:54 PM.

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