- Sab Jun 04, 2016 11:57 am
#533826
Este articulo me ha parecido muy interesante:
http://www.ei-resource.org/easyblog/ent ... n-barrier/
La mayoria de los tratamientos que tomamos para la AGA tienen un impacto en nuestro sisitema hormonal, pero pueden tener un impacto mucho mas negativo en nuestro cerebro.
Por todos es bien conocido el mecanismo por el cual el finasteride produce una disfunción del SNC (el temido brain fog y otros desordenes).
El finasteride encuentra facilidad para traspasar la bbb (blood brain barrier o barrera hematoencefálica).
Resumiedo el mecanísmo:
http://www.hairlosshelp.com/forums/mess ... adid=85335
http://www.ncbi.nlm.nih.gov/pubmed/19655698
http://www.ncbi.nlm.nih.gov/pubmed/21122055
http://www.ncbi.nlm.nih.gov/pubmed/23890183
http://www.ncbi.nlm.nih.gov/pubmed/22939118
Mi idea de tratamiento para aquellas personas que tienen tolerancia al finasteride es que lo pueden tomar a dosis pequeñas y tópicamente (i.e. 0.05%) y utilizar otro tipo de tratamientos para complementar (melatonina, protocolos de balance de prostaglandinas, PRP, DR... ). Siempre haciendo controles hormonales (T4, TSH, T, DHT, estrogenos.. ) y tomando suplementos neuroprotectivos para mantener en buen funcionamiento el cerebro.
Saludos.
http://www.ei-resource.org/easyblog/ent ... n-barrier/
La mayoria de los tratamientos que tomamos para la AGA tienen un impacto en nuestro sisitema hormonal, pero pueden tener un impacto mucho mas negativo en nuestro cerebro.
Por todos es bien conocido el mecanismo por el cual el finasteride produce una disfunción del SNC (el temido brain fog y otros desordenes).
El finasteride encuentra facilidad para traspasar la bbb (blood brain barrier o barrera hematoencefálica).
Resumiedo el mecanísmo:
Before starting the research, I already knew that 5-alpha-reductase (5AR) has important functions in the central nervous system (CNS). So inhibiting it (by finasteride) might induce some side effects there. I will not address the possible sexual side effects but only the neurological ones. I will explain to you all what I have come up with so far. And guys: this is not looking good at all.
First of all, 5AR exists in two different isozymes: 5AR type 1 (5AR1) and 5AR type 2 (5AR2). 5AR1 is present mainly in the brain, muscle, liver and in sebaceous glands. 5AR2 is referred to as the "peripheral 5AR" since it is present mainly in the prostate, seminal vesicles, liver and hair follicles. Finasteride is a specific type 2 inhibitor and doesn't inhibit 5AR1 in significant amounts. But here comes something that not many people know: 5AR type 2 is also expressed in very significant amounts in spinal chord motor neurons, actually in similar amounts found in the prostate (Poletti et al. 2003) and could have (damn it!: WILL have) an effect there. What kind of effect this is, will be explained soon.
Something else, that many people don't know: Both isozymes of 5AR have more functions than just Testosterone (T) -> Dihydrotestosterone (DHT) conversion. They do the following conversions:
1. Testosterone -> Dihydrotestosterone
2. Progesterone -> Dihydroprogesterone
3. Deoxycorticosterone -> Dihydrodeoxycorticosterone
The latter two conversions are also inhibited by finasteride and so the production of neuroactive steroids is inhibited, since their metabolic pathway continues like this:
Dihydroprogesterone -> Tetrahydroprogesterone or also called Allopregnanolone.
Dihydrodeoxycorticosterone -> tetrahydrodeoxycorticosterone
These converions are catalyzed by an enzyme called 3-alpha hydroxysteroid dehydrogenase (3-alpha HSD).
You can read about these neuroactive steroids on wikipedia in order to get a rough idea about them:
Tetrahydrodeoxycorticosterone
Allopregnanolone
Altough it states there, that Tetrahydrodeoxycorticosterone is synthesized by 5AR1 in the brain, this is only partially true since, as explained above 5AR2 is also present in the CNS namely in the motor neurons of the spinal chord.
Now we come to the REAL concern: The inhibition of Allpregnanolone production. Altough Allopregnanolone can be produced in the brain by 5AR1, the CNS is also dependent on peripheral 5AR2. I quote from "Implications of neuroimaging for the treatment of epilepsy":
"Allopregnanolone formed in peripheral tissues readily enters the brain where it acts to enhance activation of GABA. A receptors" (William H. Theodore, MD; Clinical Epilepsy Section NIH Bethesda, MD).
Now to repeat again: Finasteride definitely inhibits allopregnanolone production in spinal chord motor neurons where mainly 5AR2 is present and also reduces allopregnanolone levels in the brain and other parts of the CNS since these parts are dependent on peripheral 5AR2 conversion of progesterone to dihydroprogesterone which is then converted to allopregnanolone by 3-alpha HSD.
The question is what the result of long-term allopregnanolone depletion is. Before you have to understand what the myelin-sheath of neurons is. The axon of neurones (both, peripheral neurons and neurons in the CNS) are surrounded by an electrically insulating layer: the myelin sheath. This is vital for fast and efficient impulse propagation on the neurons. I don't want to go into details here. Fact is: Allopregnanolone has vital function in the myelination of neurons as seen in the following studies:
When you read these, you'll see that the metabolic pathway of progesterone (inhibited by finasteride...) is vital for myelination and other functions in the CNS. In fact there are dozens of studies about the effects of progesterone metabolism and allopregnanolone on myelination.
1. Progestins and antiprogestins: mechanisms of action, neuroprotection and myelination (Link)
2. Progesterone: Therapeutic opportunities for neuroprotection and myelin repair (Link)
Quote: "Progesterone and its metabolites promote the viability of neurons in the brain and spinal cord. ".
Oh damn it! Didn't we say just before, that the motor neurons of the spinal chord expresses mainly 5AR type 2 (inhibited by finasteride)? So there will be a negative effect of myelination there for sure!
2. Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of niemann-pick C mice (Link)
3. There is also a study of Goumari et al. (didn't find it on the net) that shows the function of allorpegnanolone in myelination. Quote: "... allopregnanolone accelerated myelination ..." (Ghoumari et al. 2003b)
Alright. Let's see what the effects of demyelination are: Read Myelin . The most worrying effect is again demyelination of the motor neurons of the spinal chord which will be the effect of long term finasteride use:
"Sub-acute combined degeneration of the spinal cord secondary to pernicious anaemia can lead to anything from slight peripheral nerve damage to severe damage to the central nervous system affecting speech, balance and cognitive awareness. When myelin degrades, conduction of signals along the nerve can be impaired or lost and the nerve eventually withers."
Do you see those symptoms? Speech is affected, balance and cognitive awareness. This is exactly what you call brain fog here. The question is wheter this effect is reversable if you take finasteride for years. I certainly hope so for my friend altough, you know, neurogegeneration can really be irreversible.
Fuente:First of all, 5AR exists in two different isozymes: 5AR type 1 (5AR1) and 5AR type 2 (5AR2). 5AR1 is present mainly in the brain, muscle, liver and in sebaceous glands. 5AR2 is referred to as the "peripheral 5AR" since it is present mainly in the prostate, seminal vesicles, liver and hair follicles. Finasteride is a specific type 2 inhibitor and doesn't inhibit 5AR1 in significant amounts. But here comes something that not many people know: 5AR type 2 is also expressed in very significant amounts in spinal chord motor neurons, actually in similar amounts found in the prostate (Poletti et al. 2003) and could have (damn it!: WILL have) an effect there. What kind of effect this is, will be explained soon.
Something else, that many people don't know: Both isozymes of 5AR have more functions than just Testosterone (T) -> Dihydrotestosterone (DHT) conversion. They do the following conversions:
1. Testosterone -> Dihydrotestosterone
2. Progesterone -> Dihydroprogesterone
3. Deoxycorticosterone -> Dihydrodeoxycorticosterone
The latter two conversions are also inhibited by finasteride and so the production of neuroactive steroids is inhibited, since their metabolic pathway continues like this:
Dihydroprogesterone -> Tetrahydroprogesterone or also called Allopregnanolone.
Dihydrodeoxycorticosterone -> tetrahydrodeoxycorticosterone
These converions are catalyzed by an enzyme called 3-alpha hydroxysteroid dehydrogenase (3-alpha HSD).
You can read about these neuroactive steroids on wikipedia in order to get a rough idea about them:
Tetrahydrodeoxycorticosterone
Allopregnanolone
Altough it states there, that Tetrahydrodeoxycorticosterone is synthesized by 5AR1 in the brain, this is only partially true since, as explained above 5AR2 is also present in the CNS namely in the motor neurons of the spinal chord.
Now we come to the REAL concern: The inhibition of Allpregnanolone production. Altough Allopregnanolone can be produced in the brain by 5AR1, the CNS is also dependent on peripheral 5AR2. I quote from "Implications of neuroimaging for the treatment of epilepsy":
"Allopregnanolone formed in peripheral tissues readily enters the brain where it acts to enhance activation of GABA. A receptors" (William H. Theodore, MD; Clinical Epilepsy Section NIH Bethesda, MD).
Now to repeat again: Finasteride definitely inhibits allopregnanolone production in spinal chord motor neurons where mainly 5AR2 is present and also reduces allopregnanolone levels in the brain and other parts of the CNS since these parts are dependent on peripheral 5AR2 conversion of progesterone to dihydroprogesterone which is then converted to allopregnanolone by 3-alpha HSD.
The question is what the result of long-term allopregnanolone depletion is. Before you have to understand what the myelin-sheath of neurons is. The axon of neurones (both, peripheral neurons and neurons in the CNS) are surrounded by an electrically insulating layer: the myelin sheath. This is vital for fast and efficient impulse propagation on the neurons. I don't want to go into details here. Fact is: Allopregnanolone has vital function in the myelination of neurons as seen in the following studies:
When you read these, you'll see that the metabolic pathway of progesterone (inhibited by finasteride...) is vital for myelination and other functions in the CNS. In fact there are dozens of studies about the effects of progesterone metabolism and allopregnanolone on myelination.
1. Progestins and antiprogestins: mechanisms of action, neuroprotection and myelination (Link)
2. Progesterone: Therapeutic opportunities for neuroprotection and myelin repair (Link)
Quote: "Progesterone and its metabolites promote the viability of neurons in the brain and spinal cord. ".
Oh damn it! Didn't we say just before, that the motor neurons of the spinal chord expresses mainly 5AR type 2 (inhibited by finasteride)? So there will be a negative effect of myelination there for sure!
2. Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of niemann-pick C mice (Link)
3. There is also a study of Goumari et al. (didn't find it on the net) that shows the function of allorpegnanolone in myelination. Quote: "... allopregnanolone accelerated myelination ..." (Ghoumari et al. 2003b)
Alright. Let's see what the effects of demyelination are: Read Myelin . The most worrying effect is again demyelination of the motor neurons of the spinal chord which will be the effect of long term finasteride use:
"Sub-acute combined degeneration of the spinal cord secondary to pernicious anaemia can lead to anything from slight peripheral nerve damage to severe damage to the central nervous system affecting speech, balance and cognitive awareness. When myelin degrades, conduction of signals along the nerve can be impaired or lost and the nerve eventually withers."
Do you see those symptoms? Speech is affected, balance and cognitive awareness. This is exactly what you call brain fog here. The question is wheter this effect is reversable if you take finasteride for years. I certainly hope so for my friend altough, you know, neurogegeneration can really be irreversible.
http://www.hairlosshelp.com/forums/mess ... adid=85335
http://www.ncbi.nlm.nih.gov/pubmed/19655698
http://www.ncbi.nlm.nih.gov/pubmed/21122055
http://www.ncbi.nlm.nih.gov/pubmed/23890183
http://www.ncbi.nlm.nih.gov/pubmed/22939118
Mi idea de tratamiento para aquellas personas que tienen tolerancia al finasteride es que lo pueden tomar a dosis pequeñas y tópicamente (i.e. 0.05%) y utilizar otro tipo de tratamientos para complementar (melatonina, protocolos de balance de prostaglandinas, PRP, DR... ). Siempre haciendo controles hormonales (T4, TSH, T, DHT, estrogenos.. ) y tomando suplementos neuroprotectivos para mantener en buen funcionamiento el cerebro.
Saludos.
