#21

“Omega-3 fatty acids supplementation is associated with increased AF risk, particularly in trials that used high doses. Therefore, several factors should be considered before prescribing omega-3 fatty acids, including their dose, type, and formulation (fish, dietary fish oil supplements, and purified fatty acids), as well as patient-related factors and atrial mechanical milieu. Because the benefits of omega-3 fatty acids are dose-dependent, the associated AF risk should be balanced against the benefit for ASCVD. Patients who take omega-3 fatty acids, particularly at high doses, should be informed of the risk of AF and followed up for the possible development of this common and potentially hazardous arrhythmia.”

Omega-3 fatty acids and atrial fibrillation

I’ve used 4 grams of generic Lovaza (Omega-3 ethyl esters) for decades. They’ve dropped my triglycerides down from over 400 to 44 currently (along w/ other things like exercise) and hadn’t heard of A fib issues—I’ll have to read this closely.

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#22

It’s actually worse than that. A few years back I was on tramadol (a minor narcotic) 24/7 for a hip issue (now fixed with a shiny new titanium hip). My doc in being “cautious,” wrote a script for two days short of a month, without saying anything to me. As the months went by, I was taking 3/day as allowed but ran out and went to refill it. The pharmacist very rudely scolded me: “You must learn not to take more than allowed, you can refill it in two days.”

This confused me as I never used more than 3 per day and eventually figured out why I had run out. I was not abusing the med. But here’s the gaff–later than month I saw my Practitioner and he looked confused and said: “You’ve never had a controlled med or addiction have you?” I said, “no,” and there on the screen was a warning placed by CVS about potential overuse of narcotics."

So, somehow CVS’s database notice was folded into my medical record which btw, is actually a federal violation, but I never bothered with it. He said: “I removed that,” but I wonder.

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#23

@Justin Thanks. This is what I wanted to know …from the paper you posted

POSSIBLE MECHANISMS UNDERLYING THE ASSOCIATION BETWEEN OMEGA-3 FATTY ACIDS AND AF

It is unclear how omega-3 fatty acids increase the AF risk. Omega-3 fatty acids stabilize the cardiac membrane and protect against arrhythmias, including ventricular arrhythmias, through both direct electrophysiologic actions and positive effects on biological processes involved in atrial remodeling. However, omega-3 fatty acids have direct effects on the activity of cardiac calcium, sodium, and potassium ionic currents, which can alter the duration of the ventricular action potential [27]. Therefore, omega-3 fatty acids may promote re-entrant arrhythmias, despite being anti-arrhythmic in therapeutic conditions. Several previous studies have evaluated the electrical characteristics of the ventricular wall; few studies have evaluated how omega-3 fatty acids influence the atria.

Recently, some studies have found that PIEZO proteins mediate the effect of omega-3 fatty acids on AF [28]. The PIEZO1/2 proteins are two of the largest ion channels discovered to date, with over 2,500 amino acids arranged in 38 transmembrane helices. These proteins form homotrimeric dome-shaped structures with three upward curved propeller-like blades and a central pore during assembly. The blades flatten due to increased mechanical force, which causes the central pore to open, leading to non-selective influx of positively charged ions, such as calcium (Fig. 2). Lipids in the cell membranes regulate the conformational changes that result in the opening and closing of the PIEZO channel. Dietary omega-3 fatty acids are incorporated into the cardiomyocyte surface membranes, making them thinner and more compliant [29]. The impact of these changes varies according to the type of omega-3 fatty acid used. DHA slows down the inactivation of PIEZO1 while EPA speeds it up. Therefore, the DHA:EPA ratio might determine the overall effect. A DHA-predominant effect would result in PIEZO1 activation and increased influx of calcium and other cations (Fig. 2). Finally, these changes would prolong the action potential, increase the likelihood of delayed after-depolarizations and consequently AF, and promote calcium-dependent signaling. Other atrial cell types, such as fibroblasts, may also express mechanical stress-related signaling through the PIEZO1 channels. Atrial fibroblasts from patients with AF have higher PIEZO1 expression levels and activity than those from patients with sinus rhythm, indicating that PIEZO1 may promote atrial structural remodeling [30]. A pro-arrhythmic environment may result from changes in voltage-gated ion channels, ionic pumps, cell surface receptors, and extracellular matrix-cytoskeletal interactions. In addition, PIEZO1 channels, which are one of several cell membrane characteristics altered by omega-3 fatty acid ingestion, also create a pro-arrhythmic environment.

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#24

Glad it was useful, it’s way over my head, at least this late at night…hehe…

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#25

Justin,

Take a look at supplementing with modified citrus pectin–only the validated MCP, Pectasol. See: Google Scholar

I do not represent or benefit in any way from sale of the product. Just a functional medicine MD who cares to help. Good luck.

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#26

Thanks for the suggestion and especially the link. I could spend a lifetime reading and hypothesizing what substances would do what. Currently I do supplement with Quercetin (1 gram/day) Curcumin (1.5g/day (the real curcumin 98%) and alpha-lineoic acid, and melation (30mg currently). Additionally I do keto, fasting (I’ve fasted 44 days over the past year, mostly 1-3 day fasts) and interestingly take celecoxib for arthritis, plus rosuvastatin + metformin, all of which hinder the micro-environment of my cancer’s ability to metastasize distally.

I got a new L hip last summer and have been so enamored with it that I went on a “health kick.” losing over 60lbs, and much to my surprise at age 74 increasing my biceps over an inch in circumference, since now I could go to the gym again.

There is a formula that docs use, you plug in various items like tumor grade and Gleason scores and it gives you a number. Less than 15 would indicate a indolent (lazy) tumor, not likely to metastasize distally. My number = ~140, which made me surprised to find that the tumor had not metastasized to the bone or elsewhere (based on my psma-pet scan with I-18 as agent, which is about 80% specific, but of course would not pick up micro-metastases.

So, I have a cancer that by that formula should have metastasized distally but did not.

I suspect that my being mostly on keto for the past year + fasting + celecoxib + rosuvastatin that I may have inadvertently made it difficult for the tumor to break away to new sites.

The citrus stuff looks fascinating but there is one area of immediate concern which relates to the board in general, as in sirolimus.

Naturally, I looked into: Shall I continue to take sirolimus or stop, and what about during the radiation therapy (6-8 weeks, 5 days a week!) and what about while on ADT (Androgen deprivation)?

The Pectasol “IS” a radiation sensitizer!

Check this out, as so is sirolimus:

Early and Severe Radiation Toxicity Associated with Concurrent Sirolimus in an Organ Transplant Recipient with Head and Neck Cutaneous Squamous Cell Carcinoma: A Case Report

Ideally, a substance would sensitive cancerous cells and NOT sensitize normal, adjacent cells. There is a risk of, as the article shows, sensitizing so much that one is injured by what was a “usual” amount of radiation.

The only substance that I have seen that seems to do that is melatonin.

It’s so complex. I’ll look into the Pectasol between now and radiation as I’ll be on neo-adjuvant meds (Lupron-like meds) for 1-3 months before radiation. At $5.66/ounce (current amazon price) it’s not that expensive.

Additionally a WARNING to any on Medicare Advantage: I just had a PSMA-pet scan, unknowingly, at an non-in-network facility. My insurance allows that, but nobody told me. The problem is: Now I must pay $2,995 where had I known, I would have gone to a nearby in-network facility and have paid $250. So, I’m outt $2,800 for a scan, which, by the way could be done in Mumbai, India for $400. Same scan, same agent I-18. Welcome to America. (I am looking into challenging that bill via the No Surprise act since the entity did not give me a “Surprise Billing Form,” had they done that, I’d have stopped and used Shield imaging which is nearby and in-network.

I found this, it’s free, all about pectins including modified pectins

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#27

I am doing Rapamycin via a prescription with my primary care doctor so she is already in the know. I did share the information with my Cardiologist along with the TRT stuff I am exploring. He was not judgmental at all and shared some of his perspective on both. He wasn’t concerned by any of it. I felt better not carrying a secret and want to maximize the wisdom of my providers as much as I can.

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#28

I have a new PCM, I was moved form my old one whom I could talk to about anything. (sigh.) My new one is ok but I don’t tell him about Rapamycin. I like him, but he is most definitely a stay within the lanes doc. I’m sure my old one would have been ok with it and asked me some questions about what I knew.

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#29

I am in the it depends camp. I did not tell my insurance provided assigned primary care physician. He is conservative. I also might not share if I if I went to the emergency room for a trauma type injury unless it required other medication. I have spoken with a physician about testosterone, given his knowledge about anti-aging protocol, I freely disclose my, 6 mg a week dosage, with a rest month every month. He had no objections.

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#30

Totally agree w/ CronosTempus:

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#31

I tried to get my doctor to prescribe it initially and he checked with his indemnity insurance. Apparently I can only get it from specialist. Australian medical rules are kinda archaic. Anyway I told him I’m going to get it from India. He is fine with it. He is the one that orders the blood test for me weekly. I don’t have any another major issues other than being prediabetic and getting psoriasis and gout. He is trying to find a way for me to get it locally. It is a lot cheaper. $20 USD for 100 X rapamune 1mg or 2mg. Hopefully in a few more months.

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#32

I have advanced ovarian cancer 12 years ago and I am one of the lucky ones. I wasn’t on Rapa then but have now been on it for 2 years. I personally did not share any of the supplements and meds I took: including metformin, celecoxib, IV Vit C therapy, mistletoe… they might not have liked it and I probably would have been kicked off the clinical trial I was on. Just my opinion, they don’t have an open mind about those things. I did talk with a homeopath about what I was doing and worked with him on meds and integrative therapy before, during, and after chemo and surgery. :slight_smile: I hope this helps!

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#33

Cronos Tempi, you covered most all my thoughts and more! I don’t have to say much of anything. I will, however, note that my doctor is around 20 years younger than me and does fine within the realm of standard medical practice, but she is not in my corner when it comes to trying any off-label use of any relatively harmless drug that my research says may be helpful for me. I suspect part of the problem may be that she sees me as old and not smart enough to really understand the research I read. On the other hand, I see her as young and inexperienced, but valuable if I need traditional medicine. So, no I do not share any of my off-label use of medicines. It just presents too many potential problems for her and for me. And, I certainly do not want any of my personal off-label medical information put into a medical record. Once it gets into a computer system it’s there forever and likely to spread.

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#34

I know almost nothing about cancer, except that there are some cancers that manipulate (inhibit / enhance --I don’t know) the cellular mTOR systems. If I were in your boat, I would want to learn all about that stuff first, because it might be that mTOR inhibition is already in your Cancer’s bag of tricks, and Rapamycin might not be good at all. I don’t know enough to say do or don’t, but it kinda sounds like you don’t either.

#35

Hi Justin,

Just doing some catch-up reading and came across your post.
If you are going to have radiotherapy you might be interested to know that metformin is a known “radiosensitiser”. That is; there are papers in the literature that describe how metformin makes cancer cells more prone to die from exposure to radiation. Even better, it sensitises cancer that has already become resistant to chemotherapy or radiotherapy.
Your question about Sirolimus is more difficult to answer. Ionising radiotherapy works by the radiation creating radicals (principally from water molecules so they would be hydroxyl radicals if I remember my undergraduate chemistry). The radicals then react with any nearby molecule they encounter. In dividing cells this includes DNA. Damage enough DNA and the cell dies. The principle is that cancer cells are rapidly dividing so more likely to be affected by radicals than normal cells. But some normal cells divide fairly often and they are affected, too. This is why radiotherapy often causes diarrhoea because intestinal lining cells are affected. Chemotherapy often causes hair loss because hair follicles are affected.
My take is that I would be reluctant to take something that would slow down the rate of cell division. It might seem like giving the cancer free rein to divide, but that’s a Trojan horse, because then the radiotherapy has a better chance to act. “When is a gift not a gift?” (Baron Harkonnen, Dune).

Remember: not medical advice and good luck with your treatment!

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#36

I’m still doing my 6mg/week sirolimus. For my CaP(rostate) I’ll do radiation + ADT (androgen depravity torture) (ok, androgen deprivation treatment). Sirolimus is a serious radiation sensitizer, therefore I will stop using it for the weeks that I received irradiation. For the ADT which is often 1-3 (horrifying) years, I’m not sure. I visit with a world-renowned medical oncologist at Dana Farber this upcoming week and I’ll ask her. I’m guessing that the answer will likely be “unknown,” re the ADT.

Even the radiation, even though sirolimus is a sensitizer, the only data (negative) is from transplant patients who are taking sirolimus continually, no pulsing it, as we do.

Early and Severe Radiation Toxicity Associated with Concurrent Sirolimus in an Organ Transplant Recipient with Head and Neck Cutaneous Squamous Cell Carcinoma: A Case Report

Melatonin appears to be a sensitizer too, but not to the same level, and seems to sensitize against cancer cells, while not doing so with normal cells.

My rad-doc ain’t gonna want to deal with sirolimus and I’ll err on the side of caution and discontinue it for the duration.

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