Yes, I believe the effect of angiotensin receptor blockers (ARBs) like Benicar on the VDR has not been demonstrated empirically, but only in silico studies involving computer modeling of the molecular interactions of ARB drugs and the vitamin D receptor, done by Marshall and colleagues. I don't know anything about such molecular modeling, and how reliable it is.
It's interesting that ARB drugs (which are just regular blood pressure drugs) have very weird Herx-like effects when given to patients with certain chronic diseases, including sarcoidosis and ME/CFS.
Medicine already knew about the weird effects of ARBs in patients with certain chronic diseases (I can't find a reference to this ARB phenomenon at the moment).
It's the strange reaction to ARBs in patients with chronic diseases that Marshall became fascinated with, and I believe this led to his investigation of the VDR in sarcoidosis. I think eventually he then came up with this idea of the intracellular bacteria linked to sarcoidosis turning off the VDR for immune evasion purposes, and Benicar switching it back on again, thus leading to a sudden immune response against these bacteria.
Marshall called these weird effects the "immunopathology" symptoms of the Marshall Protocol (like exacerbation of existing symptoms, fever, pain, body aches, light sensitivity requiring dark glasses); but these effects are not specific to the Marshall Protocol; as I understand it, they are what ARBs cause in patients with chronic diseases.
Yes, I believe the effect of angiotensin receptor blockers (ARBs) like Benicar on the VDR has not been demonstrated empirically, but only in silico studies involving computer modeling of the molecular interactions of ARB drugs and the vitamin D receptor, done by Marshall and colleagues. I don't know anything about such molecular modeling, and how reliable it is.
It's interesting that ARB drugs (which are just regular blood pressure drugs) have very weird Herx-like effects when given to patients with certain chronic diseases, including sarcoidosis and ME/CFS.
Medicine already knew about the weird effects of ARBs in patients with certain chronic diseases (I can't find a reference to this ARB phenomenon at the moment).
It's the strange reaction to ARBs in patients with chronic diseases that Marshall became fascinated with, and I believe this led to his investigation of the VDR in sarcoidosis. I think eventually he then came up with this idea of the intracellular bacteria linked to sarcoidosis turning off the VDR for immune evasion purposes, and Benicar switching it back on again, thus leading to a sudden immune response against these bacteria.
Marshall called these weird effects the "immunopathology" symptoms of the Marshall Protocol (like exacerbation of existing symptoms, fever, pain, body aches, light sensitivity requiring dark glasses); but these effects are not specific to the Marshall Protocol; as I understand it, they are what ARBs cause in patients with chronic diseases.
Thanks Hip!In the Marshall Protocol, you are taking the drug Benicar which activates the vitamin D receptor (VDR), so as I understand it, even if your vitamin D levels are low, you will still have VDR activation from Benicar.
The overall idea of the Marshall Protocol is not to reduce VDR activation, but to increase it. Taking Benicar and avoiding vitamin D is supposed to serve that purpose of increasing VDR activation. Activating the VDR releases the anti-microbial peptides beta-defensins and cathelicidin.
I am not sure if I understand the mechanics, but Dr Marshall said something about the inactive form of vitamin D (called 25-D) being an antagonist to VDR, whereas the active form (called 1,25-D) is a VDR agonist, and that when too much 25-D binds to the VDR, it inactivates this receptor, and stops 1,25-D from binding to and switching on the VDR.
So when people say that the Marshall Protocol is wrong because vitamin D is essential, I don't think they've understood that in theory at least the MP aims to increase VDR activation.
Whether that theory is right is another question, but I don't think we should throw the baby out with the bathwater when it comes to chronic diseases, the vitamin D receptor, and intracellular infections.
Dr Trevor Marshall developed his protocol originally to treat his sarcoidosis, which is associated with an intracellular L-form infection of the bacterium Propionibacterium acnes. Thus antibiotics make sense in this context.
Marshall also noticed that his sarcoidosis was made worse after strong sunlight exposure (this was in Australia), and that's where the sunlight and vitamin D avoidance started. In sarcoidosis, vitamin D metabolism is abnormal, because this disease creates high levels of the enzyme which converts vitamin D into its active form. I don't understand the whole story, but possibly his sun avoidance may make sense in the context of sarcoidosis.
However I don't agree with Trevor Marshall's idea that whole swathes of diseases, including ME/CFS, are caused by intracellular bacterial infection, nor the idea that vitamin D levels are a central factor in these many diseases.
Don't get me wrong, my view is that many chronic diseases will likely turn out to be caused by chronic infection (in conjunction with other causal factors), but there are more infections to consider than just L-form bacteria.
In particular, in terms of tissue evidence, ME/CFS is mainly linked to intracellular enterovirus infection; but there's no evidence of an intracellular bacterial infection in ME/CFS, except in the small subset of cases linked to Chlamydia pneumoniae.
However Trevor Marshall was adamant (I am not sure if he still is), that chronic viral infections were not the cause of ME/CFS, and it was all down to L-form bacteria. I think viruses not intracellular bacteria are likely the key to ME/CFS.
So if we take away the antibiotics, and take away the sunlight and vitamin D avoidance, it's possible Benicar's activation of the VDR alone may still have some benefit against viral infection.
Some viruses have been shown to block or down-regulate the VDR, for immune evasion purposes. EBV blocks the VDR to prevent apoptosis, and CMV down-regulates the VDR.
The defensins that are released by VDR activation are shown to have antiviral effects: they are antiviral for HSV and CMV, and antiviral for CVB.
Thus a blocked VDR may turn out to play a role in maintaining chronic viral infection or long-term viral latency, and activating the VDR may thus have antiviral benefits.
Most of what you say about the treatment and the science behind it here is accurate, and I really appreciate you taking the time to explain this calmly! But yes to clarify: we absolutely think that persistent viruses can play a role in ME/CFS, and in fact, viruses are some of the main pathogens that deregulate VDR receptor activity
