Hip
Senior Member
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@nandixon
Well spotted. So we can perhaps assume a factor of 2 increase in GLT-1expression from telmisartan. I think telmisartan is the only ARB proven to cross the blood-brain barrier. And if I remember rightly, the jury is still out on how well losartan crosses the BBB. Olmesartan (Benicar) crosses the BBB poorly.
I guess this 2-fold increase in GLT-1 is less that the 3 to 4-fold increase that some antibiotics achieve, but ARBs are probably better drug to take on along term basis.
I have tried a number of ARBs in the past. Most notably my 2 month trial of Benicar, to try out the Marshall Protocol (MP). This involved taking 40 mg of Benicar 3 times a day.
I did not take antibiotics on my version of the MP, as I think my ME/CFS is most likely underpinned by an intracellular non-cytolytic enterovirus infection, rather than an intracellular bacterial infection that Trevor Marshall assumes is responsible for a whole raft of chronic diseases.
Interestingly, cathelicidin, one of the two intracellular antimicrobial peptides the MP is supposed to up-regulate inside the cell, enables TLR-3 to respond to dsRNA. This may be useful, because the non-cytolytic enteroviruses linked to ME/CFS are in part thought to comprise dsRNA, and TLR-3 senses the presence of viral dsRNA in a cell, and then triggers the interferon response to destroy this dsRNA.
So conceivably, by inducing cathelicidin (which Benicar does via VDR activation), Benicar may usefully ramp up the interferon response against non-cytolytic enteroviruses. And in fact there are studies showing that ARB drugs due seem to ameliorate enterovirus infections:
This study found that Benicar reduced the number of viral genomes found in acute coxsackievirus B myocarditis (which enterovirus experts think may be a good model to study the coxsackievirus B infections found in ME/CFS).
Losartan was found to ameliorate chronic coxsackievirus B myocarditis (in chronic CVB myocarditis, there are no viral particles, only the intracellular non-cytolytic enteroviruses).
I wonder whether taking Benicar intranasally might increase BBB penetration, and so help target any coxsackievirus B infections in the brain. Or possibly switch to losartan, which probably more easily crosses the BBB.
Here are the estimated VDR activation abilities of various ARBs:
You see that telmisartan binds to the VDR strongly (as it has the lowest Ki value for the VDR). Olmesartan (Benicar) binds to the VDR less strongly.
I found that I did become pretty light sensitive after two months on the MP, the most common side effect of the MP. I had to wear sunglasses on sunny days. I am not sure if that response indicates the MP was working. I wonder if healthy people would also become light sensitive if they took this dose level of Benicar.
Other than that I found no other side effects from the MP. I don't think my ME/CFS was improved after two months on the MP, but I did get the impression that my anhedonia and blunted affect (emotional flatness) symptoms were slowly improved by the MP. These anhedonia symptom I have as a comorbid condition to ME/CFS; they seemed to be triggered by the virus that precipitated my ME/CFS.
I also tried telmisartan, as it crosses the BBB easily, but interestingly this had the opposite effect, and worsened my anhedonia after just 2 days of 40 mg daily. I felt an unpleasant sort of mental anhedonic numbness with telmisartan, so I stopped it. I repeated this a few times, but got the same results.
Benicar is probably something I should try again, because the last time I tried it was 5 or 6 years ago. And you are supposed to do the MP for longer than just 2 months.
Well spotted. So we can perhaps assume a factor of 2 increase in GLT-1expression from telmisartan. I think telmisartan is the only ARB proven to cross the blood-brain barrier. And if I remember rightly, the jury is still out on how well losartan crosses the BBB. Olmesartan (Benicar) crosses the BBB poorly.
I guess this 2-fold increase in GLT-1 is less that the 3 to 4-fold increase that some antibiotics achieve, but ARBs are probably better drug to take on along term basis.
I have tried a number of ARBs in the past. Most notably my 2 month trial of Benicar, to try out the Marshall Protocol (MP). This involved taking 40 mg of Benicar 3 times a day.
I did not take antibiotics on my version of the MP, as I think my ME/CFS is most likely underpinned by an intracellular non-cytolytic enterovirus infection, rather than an intracellular bacterial infection that Trevor Marshall assumes is responsible for a whole raft of chronic diseases.
Interestingly, cathelicidin, one of the two intracellular antimicrobial peptides the MP is supposed to up-regulate inside the cell, enables TLR-3 to respond to dsRNA. This may be useful, because the non-cytolytic enteroviruses linked to ME/CFS are in part thought to comprise dsRNA, and TLR-3 senses the presence of viral dsRNA in a cell, and then triggers the interferon response to destroy this dsRNA.
So conceivably, by inducing cathelicidin (which Benicar does via VDR activation), Benicar may usefully ramp up the interferon response against non-cytolytic enteroviruses. And in fact there are studies showing that ARB drugs due seem to ameliorate enterovirus infections:
This study found that Benicar reduced the number of viral genomes found in acute coxsackievirus B myocarditis (which enterovirus experts think may be a good model to study the coxsackievirus B infections found in ME/CFS).
Losartan was found to ameliorate chronic coxsackievirus B myocarditis (in chronic CVB myocarditis, there are no viral particles, only the intracellular non-cytolytic enteroviruses).
I wonder whether taking Benicar intranasally might increase BBB penetration, and so help target any coxsackievirus B infections in the brain. Or possibly switch to losartan, which probably more easily crosses the BBB.
Here are the estimated VDR activation abilities of various ARBs:
You see that telmisartan binds to the VDR strongly (as it has the lowest Ki value for the VDR). Olmesartan (Benicar) binds to the VDR less strongly.
I found that I did become pretty light sensitive after two months on the MP, the most common side effect of the MP. I had to wear sunglasses on sunny days. I am not sure if that response indicates the MP was working. I wonder if healthy people would also become light sensitive if they took this dose level of Benicar.
Other than that I found no other side effects from the MP. I don't think my ME/CFS was improved after two months on the MP, but I did get the impression that my anhedonia and blunted affect (emotional flatness) symptoms were slowly improved by the MP. These anhedonia symptom I have as a comorbid condition to ME/CFS; they seemed to be triggered by the virus that precipitated my ME/CFS.
I also tried telmisartan, as it crosses the BBB easily, but interestingly this had the opposite effect, and worsened my anhedonia after just 2 days of 40 mg daily. I felt an unpleasant sort of mental anhedonic numbness with telmisartan, so I stopped it. I repeated this a few times, but got the same results.
Benicar is probably something I should try again, because the last time I tried it was 5 or 6 years ago. And you are supposed to do the MP for longer than just 2 months.
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