A new possibility for treating AF ?

After just seeing Jackie's post in another thread, I am now leaning towards this as a good possibility to treat AF.

George - this may help explain why fasting/autophagy may have helped your friends AF as the process is the same.

This may also be why the work of Prash Sanders shows that weight loss is effective for AF

[www.sciencedaily.com]

I am already in day 7 of using fisetin and am hoping to see if PCP can help me get D+Q for hit and run approach (not all at the same time) D is expensive but the protocol only calls for 9 100mg pills over 3 weeks.

28 day of fisetin 500mg bid is less than $100.

The best thing is (so far appears to be) very little risk as senolytics only target senescent cells.

Given:

• atrial fibrosis is causal for AF, [www.ncbi.nlm.nih.gov]
• fibrosis is mediated by senescent cells, [www.ncbi.nlm.nih.gov]
• senolytics target senescent cells, [www.ncbi.nlm.nih.gov]
• use of a senolytic could reduce AF and has been shown to in vivo (heart study below)

Senolytics noted: fisetin or dasatinib + quercetin

Studies:
[pubmed.ncbi.nlm.nih.gov]
[www.ncbi.nlm.nih.gov]
[www.ncbi.nlm.nih.gov]

A study on the heart:
[pubmed.ncbi.nlm.nih.gov]
Atrial inflammation and fibrosis are the critical processes involved in atrial fibrillation (AF) after myocardial infarction (MI). Fisetin is a dietary flavonoid that has shown forceful anti-inflammatory and anti-proliferative properties in diverse models of disease. However, fisetin's role in atrial inflammation, fibrosis, and AF vulnerability post-MI remains completely unknown.Rats were subjected to MI surgery, by left anterior descending coronary artery ligation or sham operation, and treated with DMSO or fisetin via intraperitoneal injection. After 28 days, echocardiographic parameters were performed, and AF inducibility was tested. We further evaluated the inflammation, fibrosis of left atria (LA), and related signal pathways by RT-PCR, Western blot, and staining analysis.Compared to the MI group, fisetin treatment improved cardiac function, inhibited macrophage recruitment into the LA and production of IL-1β and TNF-α, and attenuated adverse atrial fibrosis following acute myocardial infarction (AMI). Electrophysiological recordings, using an isolated perfused heart, showed that MI-induced higher inducibility of AF and prolonged AF duration, interatrial conduction time (IACT), atrial effective refractory period (AERP) were significantly alleviated by fisetin. Mechanistically, fisetin markedly increased phosphorylated AMPK (p-AMPK) levels and suppressed NF-κB p65, p38MAPK, and smad3 phosphorylation in the LA post-MI.We demonstrate that fisetin improves LA expansion, cardiac function, atrial inflammation, fibrosis, and vulnerability to AF following MI by possibly regulating AMPK/NF-κB p65 and p38MAPK/smad3 signaling pathways.

First approximation scaling (6.2) of rat study would indicate 500-600mg fisetin BID for 28 days.

Alternate strategy of hit and run dasatinib 100mg + quercetin 1250mg (250 x 5) 3 cycles of 3 days over 3 weeks

Update: dasatinib appears to be very expensive (in the $1000s) and has a lot of interactions including Eliquis as many of us do. I think it's off the table.

About fisetin: [www.sciencedirect.com]

Goal – reduction of senescent cells/fibrosis and AF burden – possible elimination of AF?

Update Day 9 of fisetin: The only side effect to date is that I now have a body odor that resembles the smell of old people, but very strong and can't be removed by hygiene. It became noticeable on day 3 or 4 and is almost impossible not to notice (even to adapted me) on day 9. My dumb guess is it's these cells getting excreted by every mechanism possible. It's almost bad enough to make me want to stop and see if it clears.

Update Day 16 - Still doing this. The smell is gone and I am told I smell like myself again. I'm not expecting to magically go in to NSR and I doubt that even if flec or another ECV converted me I would reschedule my ablation even if not in AF. Maybe the fisetin will lead towards an easier less intrusive ablation? Wish I'd done something like this early on.

Update day 21 - Near end of cycle - I have some left over pills so just taking them until out. I don't know if it helped or not because there's no baseline. I think if I had the option of doing the D+Q and was not on any other meds I would be willing to try the cycle as described above. It's powerful stuff with a history of working on kidneys, lungs.. why not the heart?

Update 10 weeks post ablation: During my ablation I had complications which may be related to the use of Fisetin the month before the ablation. I now have some reservations that this may not be a good thing to try in the months previous to having an ablation. Completely unknown and unknowable but I had 'rare' complications that probably need some likely explanation and this might be it.



Edited 4 time(s). Last edit at 11/10/2020 01:18PM by NotLyingAboutMyAfib.

Wow! Thanks for all this great research and information with the links. Am going to read this closely. Am preparing to start Modified Citrus Pectin (waiting for it to arrive) with the goal of possibly reversing any atrial fibrosis that may already exist, so as to undo structural remodeling from afib that has occurred. So I am quite interested in this approach you are taking.

If you are taking medications, note that modified citrus pectin can slow their absorption.

I am wary of throwing too many things into the N=1 mother nature's blender at the same time. I feel like eliquis, fisetin, and quercetin (and/or MCP, serrapeptase, nattokinase, etc) all at once might be too much to handle.

A lot of what I am seeing is that many of these substances get destroyed in the stomach so are virtually worthless as supplements. Yet they keep selling them to us. Ugh...

Okay, so I'm gonna need to take a proper look at this at a time when my brain can process this much information haha

Quote
NotLyingAboutMyAfib
Goal – reduction of senescent cells/fibrosis and AF burden – possible elimination of AF?

My only comment would be that my understanding of senolytics is that usage should be cyclical, not continuous. I don't know what the optimal cycle is (I've not read all your material, yet).

Quote
Daisy
If you are taking medications, note that modified citrus pectin can slow their absorption.

Hi Daisy. Do you have more information on that? MCP does not have a CYP3A4 interaction that would interfere with medications - at least not the MCP sold as PectaSol-C, according to the manufacturer.

Or do you mean as a soluble fiber it could reduce absorption of anything consumed at same time - food or medication - because it clears out the bowel? The instructions say to not take it with food for that reason. and that would also apply to medication.

Would be interested to know what you have seen on this subject.

Late addition: Never mind. I found something online making that point: [ww5.komen.org]. It says: "Modified citrus pectin may slow or reduce the absorption of oral drugs. Caution is advised when taking medications by mouth."

I will write the company and ask them about this.



Edited 2 time(s). Last edit at 07/31/2020 06:43PM by PoetKim.

NotLying,
I too have long suspected that a lack of autophagy is behind PAF. A bit speculative on my part but I posted this in the General Health Forum a while back:

[www.afibbers.org]

“The bioactive components in fermented soy products include the fibrinolytic enzyme, nattokinase (in natto), and polyamine. The polyamine spermidine was previously found to have cardioprotective effects, with intake associated with reduced morality due to heart failure.”

So Spermidine essentially does similar things to what phytoestrogens such as Genistien and Diadazem (very high in natto) but the really interesting thing is they are all involved with Autophagy :

Autophagy is the natural, regulated mechanism of the cell that removes unnecessary or dysfunctional components. It allows the orderly degradation and recycling of cellular components.'”

All along I have suspected PAF is a form of Cancer of the electrical system of the heart and the extra circuits in our atria that our hearts produce in latter life (and are ablated by our EP's) are a result of decreasing Autophagy as we age?

It seem's ironic that PAF and Cancer strike about the same time in middle and latter life

So thinking out loud here, by increasing the amount of Autophagy with eating natto (genistein, spermidine) we are destroying these extra atrial circuits through autophargy and consequently putting PAF into remission and protecting ourselves from Cancer at the same time?

Dean

Dean, I have eaten natto for the K2 MK7 but most of the research I've seen (from memory) shows that nattokinase will not survive past stomach acid and get to where it needs to be.

George, the two studies I linked show both cyclical (hit and run) for D+Q and continuous for fisetin. I'm just taking my best guess at what will work with fisetin as it's the easiest path for right now.

But fisetin could use some help also -

[pubmed.ncbi.nlm.nih.gov]

[www.sciencedirect.com]

I just try to approximate what the papers say and fingers crossed.

My ablation is scheduled for end of August so unless there is a miracle return into NSR, there's no way of knowing if this worked. I suppose I could delay, have another ECV and see if NSR persists and then ablate.

Alternatively, there's enough time to run the D+Q cycle 3x but the marginal improvements in pulmonary performance in humans aren't that encouraging (but somewhat encouraging).

One quick caution - I am normally a very clean person with no body scent but starting about the 3rd day, I noticed some smell and the need to change clothes and shower more often. Because I swim and workout this is now 4x a day. But typically I get away with 2x a day. That's the only change I've noticed since taking fisetin.



Edited 1 time(s). Last edit at 07/31/2020 07:41PM by NotLyingAboutMyAfib.

Dean - your link was back to this thread. Please repost. Thanks

Quote
NotLyingAboutMyAfib
Dean - your link was back to this thread. Please repost. Thanks

Perhaps this is the link Dean was meaning [www.afibbers.org]

Quote
NotLyingAboutMyAfib
Dean, I have eaten natto for the K2 MK7 but most of the research I've seen (from memory) shows that nattokinase will not survive past stomach acid and get to where it needs to be.

You can buy sublingual nattokinase, in a pump spray bottle. One squirt under tongue each morning (or whenever). Bypass GI system.

Quote
NotLyingAboutMyAfib
Senolytics noted: fisetin or dasatinib + quercetin
Alternate strategy of hit and run dasatinib 100mg + quercetin 1250mg (250 x 5) 3 cycles of 3 days over 3 weeks
Goal – reduction of senescent cells/fibrosis and AF burden – possible elimination of AF?

I was debating to comment on the drug interactions of dasatinib that many folks on this forum may take with their drugs after reading this well written report, especially— and not limited to —Flecainide and Eliquis, and even supplements. If it saves even one from visiting the icu, I feel it’s worth this reply for one to check out the following links.

[www.drugs.com]

[www.drugs.com]

A total of 663 drugs are known to interact with dasatinib.

216 major drug interactions-IMHO don’t ignore, discuss with your pharmacist
434 moderate drug interactions-something to discuss with your pharmacist.
13 minor drug interactions- probably not concerned

I mention pharmacist because they must take 30 CE hours to keep their license up to date with drugs on the market plus they get daily emails regarding drugs...while many doctors get their drug info from drug sales rep at times, or they perform the same drug interaction checker without the benefit of daily drug updates.



Edited 2 time(s). Last edit at 08/01/2020 02:02AM by susan.d.

NLAMAF - In archived posts, there is reference to info on reducing and preferably, eliminating, fibrosis by systemic enzymes. One expert quoted is William Wong, ND, PhD... who has written an abundance of reports on the connection between inflammation and fibrosis. His classic report is: Fibrosis, the Enemy of Life... see this link.. and scroll down through so you see the relevancy.
[www.alkalizingnutrition.com]

I much prefer systemic enzymes rather than Rx meds as a way to avoid the side effects of drugs. Lab evaluations of inflammatory markers will help monitor progress and success once systemic enzymes are used on a daily basis.

Jackie

PS - Out of that Conference Room report... this clip...

Possible Role of Magnesium in Disorders of the Aged
by
Mildred S. Seelig, M.D., M.P.H., F.A.C.N.
GOLDWATER MEMORIAL HOSPITAL, MEDICAL DEPARTMENT
NEW YORK UNIVERSITY MEDICAL CENTER
ROOSEVELT ISLAND, NEW YORK, NEW YORK 10044

Excerpt:

Collagen, Fibrosis and Aging
"Collagen becomes more abundant, as well as more rigid, with increasing age (Hall, 1969). Among the nutrients that influence the metabolism of collagen are vitamins B6 and E, which have interrelationships with Mg. Mg deficiency increases the cardiac fibrosis... "

This makes the connection: [www.ccjm.org]

'Basic Mechanisms of Atrial Fibrillation' by David R. Van Wagoner, PhD. (Cleveland Clinic)

From other sources it appears that Mg sufficiency may reverse fibrotic changes induced by Mg deficiency. Perhaps that is why over the 2 1/2 years following final freedom from the beast there has been a gradual, slow reduction of ectopic beats until now they are virtually zero.

Perhaps the complexity of age, oxidative stress, Mg deficiency, inflammation, fibrosis, a-fib is unravelling a bit.



Edited 1 time(s). Last edit at 08/01/2020 09:38AM by Jackie.

NLAMAF - You commented to Dean:

Dean, I have eaten natto for the K2 MK7 but most of the research I've seen (from memory) shows that nattokinase will not survive past stomach acid and get to where it needs to be.

While I'm not saying that natto (food) does not work, because it definitely does for Dean and many other afibbers reporting here over the years, I have personal experience with the supplemental form of NK in what it can do to eliminate a clot that has formed... so that form does survive stomach acid and is effective.

In a 2017 post titled Clot Risk, there is a segment on my story from long ago after my first ablation with Dr. Natale (2003)... ... here's the relevant excerpt ... But, try to go to that link and read the entire report which emphasizes the importance of magnesium optimization as well.

....." My history is that I have a slightly low platelet count which made using Coumadin/warfarin difficult back when I began my afib saga (1995) which was the only anticoagulant available at the time. In desperation and after much research, I decided not to use warfarin and told my cardiologist that I would sign a waiver if needed but I was going to switch to the fibrinolytic enzymes (Nattokinase) and I hoped he wouldn’t ‘fire’ me. I didn’t have to sign a waiver and I did very well with many prolonged events during the 8 years prior to my first (Natale) ablation in 2003. For that, I did go back on warfarin and as soon as I was cleared to stop (3 months), I immediately went back to using nattokinase (NK).

Good thing, because at 103 days post-ablation, I went into Afib and was cardioverted about 30 hours later. The following week, I had the requisite spiral CT scan of the heart in preparation for the 3 month review with Dr. Natale. All was fine and I was enjoying my bliss in NSR. I had asked for and received about 6 weeks later, a copy of the CT scan report. I was shocked to see the notation that there was a clot in my heart. I called Dr. Natale’s nurse and I half-joked about the situation, saying “it’s a good thing I went back on my Nattokinase or I’d probably be dead.”

Previously, I had great confidence in the efficacy of systemic enzymes for managing clot-risk factors, but this certainly confirmed what I had learned in all my research prior to my decision to use NK instead of warfarin. I had the good fortune to have many conversations with Ralph Holsworth, DO, the NK expert in the US, and he shared volumes of research with me and his experiences using it with his patients. As a result, I offered the two Conference Room Sessions, 39 and 40 on Nattokinase. Since then, the literature continues to support the use of nattokinase as well as serrapeptase for this purpose. " end quote

Continue: [www.afibbers.org]

Jackie

I appreciate everyone's input and critique of this idea.

Like always, I think it will be hard outside of a placebo RCT to detect whether one intervention works or not because so many of us are multi-interventional.

Here's a list of things I do or don't do now vs pre AF.

1. avoid alcohol
2. avoid msg
3. avoid caffeine
4. avoid diet soda
5. avoid bread, grains, seed oils,
6. avoid hs-crp (use cpap)
7. take mg
8. take potassium
9. take ubiquonol
10. epa/dha to Steve Carr's #s (used to be more)
11. take d and check levels often
12. reduce visceral fat (down about 2lbs per dexa)
13. take fisetin

Probably many more if I thought about it. If I pop into NSR before end of August, there's no way of knowing what did it. If after August, it will be Dr. N. : )

Jackie - it will take me some time to work through all of that material.

Here's what led me to put my earlier statement in on the low bioavailability of nattokinase.

[www.sciencedirect.com]

[www.sciencedirect.com]

[pubmed.ncbi.nlm.nih.gov]

As I read it - this puts OTC nattokinase with an enteric coating (most do not) bioavailability at about 1.4%

Some more papers on the subject

CHD and failure link to senescent cells:

[sciencedirect.com]

[ahajournals.org]

[pubmed.ncbi.nlm.nih.gov]

[ncbi.nlm.nih.gov]

link between senescence and fibrosis

[pubmed.ncbi.nlm.nih.gov]

BTW.
Most of the bacteria beneficial to the intestines such as bifidus are killed in the stomach by the acid before they reach the intestines if taken orally. But natto bacteria are able to survive the journey and reproduce in the intestines where they aid digestion.

Colindo - correct. Bacillus subtilis will survive stomach acid and go on to intestines and colon.

Nattokinase needs intraduodenal administration or otherwise it's very small percentages (1.4%).