As per this talk by Robb Wolf at UCSF (at ~1 hour in), non-Western Huntington’s disease carriers don’t seem to express the disease. Since Huntington’s Disease is a rare genetic neurodegenerative disease, this is intriguing and suggests that the expression of the disease may be epigenetic. As he points out a few minutes later, tissue transglutaminase has been implicated in Huntington’s Disease. What does this have to do with epigenetics and PH?
Tissue transglutaminase is an enzyme that is responsible for modifying most of the body’s proteins. A key tenant of the “Paleo Diet” and similar metabolic/nutritional therapies is that consumption of dietary lectins found in grains and legumes play a role in the development of a variety of diseases by escaping into the bloodstream from the gut and triggering immune responses as well as interacting with the enzyme tissue transglutaminase. How it does all of this I will leave for another post, but for now, you can get the gist for this theory in this blog post and this talk by Robb Wolf.
Robb Wolf’s theory is that since tissue transglutaminase has such a vast role in the body, modifying proteins in all organs, than anything that affects tissue transglutaminase, can lead to conditions in a variety of organs, depending on the individual: heart condition, lung condition, brain condition, etc. He believes this accounts for the occurrence of autoimmune conditions such as Crohn’s disease, Celiac disease, Rheumatoid Arthritis, Alzheimer’s, and even rare diseases like Huntington’s Disease. The fact that a Google search for Huntington’s Disease + Transglutaminase leads to hits in the literature suggests that there may be something to this.
And when I mentioned Rheumatoid Arthritis above, that should give a red flag… since Rheumatoid Arthritis is implicated in PH. A quick Google search of Pulmonary Hypertension + Tissue Transglutaminase yields several hits…
If lectins from grains and legumes can interact with Tissue Transglutaminase in a negative way, and Tissue Transglutaminase is implicated in PH, then perhaps consumption of these substances may be harmful for those with or susceptible to PH?
In the case of Huntington’s Disease, it appears there is an upregulation of transglutaminase activity. It appears that the same occurs for PH.
More needs to be known about how exactly lectins interact with Tissue Transglutaminase. For example, does it upregulate or downregulate it’s activity? Regardless, however, the correlation is intriguing…
0 replies on “Lectins, Tissue Transglutaminase, & PH”
Hi – this is very interesting to me as I was specifically searching for a link between leptins and PAH. I have been diagnosed with PAH but am not typical (even my specialist says so). I developed histamine intolerance around the same time as I was diagnosed with PAH (after a sudden onset (within 2 weeks) of breathlessness, rapid heartbeat and near syncope). I already had autoimmune hypothyroidism and was just starting menopause when I got ill. I believe my restricted diet has had a positive impact on the PAH. To be honest, if it was not for the raised arterial pressures that show up during a heart catherisation, you wouldn’t know I’ve had it since 2015. My symptoms cleared up as quickly as they came, within a month of diagnosis after I drastically reduced the amount of natural dessicated thyroid I was taking to treat my condition. I have been on all of the suggested PAH meds to reduce my arterial pressures and the only ones that worked are CCBs. Coincidentally, these also reduce the amount of circulating Estradiol…which can form part of a negative feedback loop with histamine – both of which affect thyroid function…and can lead to PAH due to leukotriene activity. The fact that CCBs are suggested as leukotriene inhibitors for people suffering from Mast Cell disease/activation disorder is further evidence to me that somewhere in this estrogen/thyroid/histamine loop lies the answer to what is causing my increase in arterial pressures.
I am a lay person who understands only a fraction of the things my research turns up but I do feel I am on to something. I just wish I knew what! :)
That is very interesting, thank you for your comment. And I’m so glad that you are researching as well :) Estrogen is a bit tricky… we know estrogen plays a role in PH, but we don’t know exactly how. Estrogen has been both positively and negatively associated with PH. I think the source lies in something a bit deeper… I happen to believe autoimmunity, as well as metabolism, plays a big role. On a side note, since you mentioned autoimmune hypothyroidism, I wanted to mention to you Dr. Sarah Ballantyne at https://www.thepaleomom.com/. She has an autoimmune protocol that she developed. It might be interesting to check out. She actually suffered from Hashimoto’s and was able to put symptoms in remission. I would recommend checking out some of her work.
Thanks for the reply. There are a couple of reasons I think Estrogen (or possibly aromatase) are part of my underlying problem. The 8 week period when I got very ill was immediately after the first time I ever missed two periods due to peri-menopause. I also found out about a year later, that my house had become infested with mold during a very wet summer. I knew my home was a little prone to damp but didn’t realise that there was mold growing on my mattress (and probably inside my pillows) as well as on the hardboard undersides of my drawers and beside cabinets, as well as inside the cavities of my sofas and chairs! At one point I thought CIRS caused by the mold might be what triggered the PAH but my pressures didn’t improve once I was out of the moldy environment.
I became hypothyroid in 2007, the same year I developed a massive uterine fibroid, so there is a possible estrogen dominance link. I also had slightly increased Lymphocytes discovered at this time and had yearly blood tests to monitor the levels for 5 years. I was signed off of treatment when the levels stayed the same. A letter from a specialist unit said that I had increased T cells and B cells but they were not ‘clonal’. On any letters sent to me currently by the PH dept, they summarise this as a T-cell proliferative disorder. I now know this could be linked to Lectins and/or histamine, or aromotase/estrogen.
When I got ill in 2015, I also started becoming hyper on the NDT dose that had been fine for 5 years. I stopped it and went on to 1 x 100mcg Levothyroxine. I know now because of my research that excess T3 can affect estrogen levels. My initial 6 minute walk test result when I was first diagnosed was only 218m. That was Sept 2015. By the time it was checked again at the end of October, it had gone up to 450m. The only changes I had made during that time was to reduced my NDT (I refused the PAH specific meds at that point because I was convinced the docs were wrong about the diagnosis. In fact, I still am. I think my raised pressures are a symptom of something else).
One other bit of info that might interest you from a research point of view is that my NTproBNP level was pretty high when I first got ill. It has reduced a lot since and was at it’s lowest after I started the CCBs and my arterial pressures reduced for the first time. I stopped the CCBs for about a year because I worried about the negative reports I read about Amlodipine (and my right foot started to swell). I had no worsening of symptoms but when I had my NTproBNP level checked again, it had shot back up. I didn’t make the connection then but found out later about the link between Estrogen and PAH, and the impact CCBs have on Estrogen levels, so restarted them for that reason. When my NTproBNP was checked again, it was back down to about the level it was before I stopped taking the CCBs (I hope this all makes sense).
Since I have been taking natural progesterone, lots of my histamine issues have improved (although the flushes and night sweats are still pretty bad, if not worse). Interestingly though, my 6 minute walk test increased to 500m, the first real improvement in a year or so. I don’t know what my latest echo or NTproBNP result is yet as I am still waiting on the letter from the hospital but during the appt after my tests, the specialist said I had improved and asked me what had changed, so I guess they are happy with whatever I am doing…so much so that he said even though the recommended dose of this CCB was 20mg per day, they want me to stay on 10mg because the research has only ever been done on 20mg and 10mg might actually be enough. My next RHC will give more conclusive proof if my pressures have improved as much as my other symptoms.
I also have a looooong awaited appt with an immunologist in May, so that might bring up any genetic issues that might be the cause of my probs.
My unscientific personal theory is that my estrogen dominance is related to my mast cell issues…and those could be the cause of my PAH. So sorry to waffle on but you may get some useful info from my experience so I want to share it with someone who might be able to do some good with it.
Thanks for the Autoimmune protocol link. At the mo, I am actually pretty much gluten free because I can’t tolerate grains of any kind. Lots of other foods like potatos and rice cause me probs too so I am trying to eliminate lectins too (specifically diary). Thanks again.
Very interesting. Thank you so much for your comment, Rose :) I’m going to look into the things you said. It all sounds very interesting. There has to be something in there…
HI again – just thought I would follow up this comment as recent results have me questioning some of the conclusions I had come to, and what you said before about estrogen being protective had stuck with me. My results have arrived since I commented last and I have discovered that my NTproBNP was worse this time! Still only 47 pmol (approx 200ng/l) which is good compared to the 164pmol it was at my worst, but significantly worse than my reading this time last year of 6 pmol! There was one other time my level went up but not by as much and that was after I had been on a progesterone only pill for about 6 weeks. As I might have mentioned, I have been using progesterone cream until recently for about 6 months, when I realised it made my flushes and night sweats worse so stopped using it. This was after my last blood test had been taken.
So I looked again over the last couple of days at my research regarding the effect CCBs have on sex hormones. The drugs that showed that they reduced circulating Estradiol when tested were a different class of CCB than the one I am on, something I had not realised until now. I am on Amlodipine and now I am looking with fresh eyes, I am finding lots of evidence to support research that suggests they can affect male fertility because they lower LH, FSH and Testosterone. So I am wondering if a menopausal woman like me (who recently discovered docs didn’t tell me my FSH was in the 50’s a few months before I started to get ill in 2015), might be improving because they are taking something that lowers FSH (and therefore changes my estrogen/testosterone ratio). I wonder if this might be the reason my hemodynamics improved after starting it?
The thing is, my PAP has stayed in the mid-30s since I started CCBS but I became convinced they were not helping so stopped taking them for 6 months last year. When I was tested again, my PAP was the same as when I was taking them, and my NTproBNP was then at it’s lowest result of 6 pmol. To me, this proves that the CCB has nothing to do with my BNP result. My BNP level began to reduce immediately after I got ill and stopped taking Natural Dessicated Thyroid and continued to fall until I took the mini pill, as mentioned above.
I wonder if the research that shows PAH reversal in rats after estrogen is administered – a reversal that continued even after the estrogen treatment was stopped – might explain why the Amlodipine brought my pressures down by a certain amount but then stopped? Maybe it is only half of the hormonal puzzle that might have caused my condition…and the typical reduction of estrogen that happens in menopause is the underlying cause?
I won’t restate a lot of the stuff I have already told you (as I am sure you are losing the will to live by now, lol) but it might be worth mentioning that my diet was full of xenoestrogens at the time. I was also taking 5 grains of NDT (which in hindsight could have been needed because my estradiol (which increases t4 to t3 conversion) was falling). This hormone stuff is all very confusing and without a science background, I am struggling to understand it but I think some research I just found suggests that hight levels of T3 can increase SHBG which then attaches to hormones and makes them inactive?? I will need to find some simpler research to see if am understanding that correctly. I do know there is a strong link between estrogen and thyroid.
One other thing that might be related to what I told you in the last paragraph, is that I had just started a new batch of NDT when I got ill initially. At first, I was convinced it was a rogue batch that had caused the sudden onset of PAH (as you know, hyperthyroidism can cause it) which is why I stopped it and started taking synthetic T4 (under doctor’s advice). When my symptoms and 6MWT drastically improved, but my arterial pressures did not, it was assumed it could not have been the cause.
One final thing to mention – I had a thyroid function test a couple of months ago because I was feeling lousy. My results were way out of range and showed that I was severely undermedicated on my usual dose. Maybe that was down to the increased progesterone opposing the little amount of estrogen I have? Anyway, when tested 7 weeks later, my results were in range. I had no increased my dose but I had stopped the progesterone oil.
Ok – another long, and complicated post. Maybe I will never know the cause of my illness, or maybe it started for one reason and continued for another? Or maybe issues that were masked by taking NDT during peri-menopause manifested suddenly once my estrogen dropped just a little bit more? I would like to find out one day.
By the way, I am not sharing all of this info with you so you can cure me, lol. I just want to contribute any info that might help you in your research, and benefit from any advice you might think is useful (like your comment in an earlier post about estrogen).
Thanks again and, as usual, no need to reply if you don’t have the time.