talk about prevention strategies?

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Fiver
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talk about prevention strategies?

Post by Fiver »

Hi everyone, I hope all is well.

Anyone want to talk about prevention strategies?

Here’s mine:

Fish oil, vitamin D, atorvastatin 10mg

sulforaphane and sodium butyrate, hoping these HDAC inhibitors fix endosomal/lysosomal cycling.

Tried homotaurine for a while, would like to restart that.

A generally good diet, fasting from 7pm to 11am, with a keto diet for stretches but finding that hard to sustain.

Exercise and stress relief plans are going very well.

My concern and reason for writing is that my gut these days tells me this isn’t enough to make much of a difference. I feel like I need to step up my game. I’m 53 and feeling like there is less time to bend the curve toward healthy cognition in later life. But I’m not sure what to add to my plan.

I’m also wondering if exogenous ketones (the sodium butyrate) and the keto are redundant. I find the keto diet gives me lots of GI issues.

I lost the one doctor I had who I could really discuss these things with - I need to find another good, knowledgeable one.

Hit me with thoughts, advice, etc. Feel free to get technical if you want. I’m a biochemist working in a related field - though I feel like I know almost nothing useful and find it hard to keep up with the new developments.
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Re: talk about prevention strategies?

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My prevention strategy looks quite different from yours. Here are the main components:
  • Whole foods plant based diet low fat, low sugar
  • Pre-biotic fiber added to meals for gut health
  • Good sleep (taping mouth)
  • Moderate exercise daily or every other day (but can always do more)
  • Red light therapy
  • Bio-identical hormones
  • Current supplements: Omega 3, CoQ10, plasmologens, D3, K2, pregnenolone, DHEA, B complex, NAC, astaxanthin, alpha lipoic acid, choline, zinc, DIM, magnesium, and Ca-akg
I eat three meals a day. I believe in breakfast. I fast from 5-6 pm to 8 am. I have a low bmi and, per Valter Longo, fasting isn't for me.
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Julie G
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Re: talk about prevention strategies?

Post by Julie G »

Hit me with thoughts, advice, etc. Feel free to get technical if you want. I’m a biochemist working in a related field - though I feel like I know almost nothing useful and find it hard to keep up with the new developments.
Hi there, fiver! Your regimen looks good. A few thoughts:

-E4, in a dose dependent fashion, has been shown to impair the brain's ability to effectively use glucose — hence the importance of getting into ketosis at least once daily (1.0-1.5 mM), not chronically. (Read more here.) Have you ever measured your ketones? The best time would be right before you break your fast. My guess is that your fasting and exercise alone may be getting you there. My "keto" diet isn't strict at all because I can achieve ketosis via fasting and exercise.

-Have you ever measured your homocysteine? That's an important biomarker to track as it's associated with cognitive decline, brain atrophy, white matter hyper intensities, etc. Most of us end up needing to supplement B-12, folate and B6 (as P5P).
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Re: talk about prevention strategies?

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Julie G wrote: Tue Apr 09, 2024 5:24 am -Have you ever measured your homocysteine? That's an important biomarker to track as it's associated with cognitive decline, brain atrophy, white matter hyper intensities, etc. Most of us end up needing to supplement B-12, folate and B6 (as P5P).
Below is a quote homocysteine from "Breaking Alzheimer’s: A 15 Year Crusade to Expose the Cause and Deliver the Cure" by Dayan Goodenowe, Chapter 19.

“Section 8: Methyltransferase/ Choline System The methyltransferase system is a critical nexus for multiple essential biochemical systems. Its core purpose is to efficiently utilize the terminal methyl group from the essential amino acid methionine as a methyl source for numerous biological processes. The two main methylation pathways are choline synthesis for biological membranes and neurotransmitter synthesis and creatine synthesis for muscle building and maintenance. Choline plasmalogens are exclusively made via the methyltransferase system. The key components of the system are a non-deficient supply of methionine and key vitamins and cofactors such as B12, B6, and folate; efficient recycling of methionine to preserve and reduce daily dietary methionine demands; and sufficient dietary supply of the main methyltransferase products choline and creatine to reduce the endogenous synthesis load. Methionine is converted to S-adenosylmethionine (SAM), which is the actual methyl donor. SAM is used by numerous enzyme systems throughout the body. Regardless of the enzyme system that uses SAM, after it donates its methyl group it is converted to S-adenosylhomocysteine (SAH). SAH is then metabolized to homocysteine. Homocysteine is essentially a biomarker of SAH. Methionine is an essential dietary amino acid because of the body’s reliance on it for numerous methyltransferase reactions. To prevent methionine depletion caused by overactive methyltransferase activity, the body need to be able to sense the amount of methyltransferase occurring and shut it down if it is overactive. SAH serves this purpose. SAH is a very potent methyl transferase inhibitor. If SAH builds up, methyltransferase activity is shut down. Therefore, to maintain methyltransferase reserve capacity, you need low resting SAH levels–as measured by low homocysteine. Homocysteine can either be converted back to methionine (the preferred path) or metabolized further to cysteine, which is then used to make glutathione. The conversion of homocysteine to cysteine irreversibly depletes methionine. Homocysteine recycling enzymes require methyl-tetrahydrofolate (mTHF), vitamin B12, and vitamin B6. Deficiencies in these cofactors result in inefficient recycling of homocysteine. Excessive methylation demand results in depletion of these vitamins and cofactors. Dietary supply of choline and creatine naturally reduces methyltransferase demand and naturally lowers SAH and homocysteine. Lowering homocysteine by solely increasing homocysteine recycling using high dietary mTHF and vitamin B6/ 12 eliminates the diagnostic utility of homocysteine and potentially exacerbates the negative effects of overactive methylation. Dietary supplementation of methionine should be approached with caution. Supplementation with N-acetylcysteine is preferred as it preserves and prevents excessive conversion of homocysteine to cysteine and ensures healthy glutathione levels. Phosphatidylcholine is the second nexus in this system. Phosphatidylcholine is essential and critical, and the body will sacrifice other systems to ensure adequate levels. Phosphatidylcholine is used to create sphingomyelin, which is another critical membrane lipid that also contains choline. Phosphatidylcholine combines with ceramides to create sphingomyelin. Sphingomyelin is broken down to create PC and ceramides. High homocysteine is associated with increased dementia, metabolic syndrome, and all-cause mortality risk. Elevated ceramide levels are associated with increased risk of cardiovascular disease and neurodegenerative disease. Higher levels of phosphatidylcholines and sphingomyelins are associated with reduced risk of neurodegenerative diseases. ProdromeScan measures total phosphatidylethanolamines, phosphatidylcholines, sphingomyelins, ceramides, and homocysteine to obtain an objective evaluation of the methyltransferase system function and reserve capacity.”
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Fiver
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Re: talk about prevention strategies?

Post by Fiver »

Hi Plumster, thanks for sharing your plan.
  • Whole foods plant based diet low fat, low sugar
At various times, sometime lasting for years, I've done the Med Diet and ketoflex variations, with or without 16h fasting. Recently I've been really convinced that ketogenic diets have good benefits, so I went that way again.
  • Pre-biotic fiber added to meals for gut health
I have not done this, but know others who do and it makes sense to me.
  • Good sleep (taping mouth)
Oh are you a mouth breather too? :) Does taping work?
  • Moderate exercise daily or every other day (but can always do more)
I do this, and enjoy it.
  • Red light therapy
Have not tried, but have played around with the 40hz light and sound apps.
  • Bio-identical hormones
  • Current supplements: Omega 3, CoQ10, plasmologens, D3, K2, pregnenolone, DHEA, B complex, NAC, astaxanthin, alpha lipoic acid, choline, zinc, DIM, magnesium, and Ca-akg
I currently do omega-3s and D3. In the past I have used Q10, B complexes, and alpha lipoic acid, among others. Why didn't I continue? I guess because I didn't have evidence to know it was helping. Maybe I got lazy.

I eat three meals a day. I believe in breakfast. I fast from 5-6 pm to 8 am. I have a low bmi and, per Valter Longo, fasting isn't for me.
[/quote] I have gotten used to skipping breakfast and fasting. Work often gets busy enough that often I don't eat until 2 or 3pm. Probably not ideal.
Fiver
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Re: talk about prevention strategies?

Post by Fiver »

Hi Julie,

Thanks for your message. I hope all is well.
Julie G wrote: Tue Apr 09, 2024 5:24 am
-E4, in a dose dependent fashion, has been shown to impair the brain's ability to effectively use glucose — hence the importance of getting into ketosis at least once daily (1.0-1.5 mM), not chronically. (Read more here.) Have you ever measured your ketones? The best time would be right before your fast. My guess is that your fasting and exercise alone may be getting you there. My "keto" diet isn't strict at all because I can achieve ketosis via fasting and exercise.

-Have you ever measured your homocysteine? That's an important biomarker to track as it's associated with cognitive decline, brain atrophy, white matter hyper intensities, etc. Most of us end up needing to supplement B-12, folate and B6 (as P5P).
Good question. In the past I used a ketone meter. Then after a while I just got so used to the 16:8 fasting and knowing I was in the zone I didn't measure anymore. This time I was making adjustments without checking. Not good. Maybe I thought I could feel it - sometimes I could. But I should get back to tracking it. Thanks for reminding me that fasting and exercise might get me most of the way there.

I will think about how to do this with the sodium butyrate I am taking now, perhaps I will do it without the exogenous butyrate and then with it to see if it is really necessary.

I used to pay attention to homocyteine levels and did use the Bs to optimize that, though it was never too bad. I'll go back and check my recent numbers.

Oh my, I feel like I really do need to refresh my plan. It will be a good thing.
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Re: talk about prevention strategies?

Post by Julie G »

Below is a quote homocysteine from "Breaking Alzheimer’s: A 15 Year Crusade to Expose the Cause and Deliver the Cure" by Dayan Goodenowe, Chapter 19.
Amazing share, Tincup. I love the details of this stuff! Understanding the why helps us all refine our protocols.
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Re: talk about prevention strategies?

Post by antimatter37 »

Here is my prevention strategy:

1. Exercise. I have been a moderate exerciser for 50 years. Mostly jogging. Now, at age 68 I jog very slowly 3 times per week for about 4.5 miles at a time. I throw in 2 intervals 3 minutes in length where I try to get my heart rate to over 140.

2. Keto. I have been using a keto diet yearly or every other year 1-3 months in length for 20 years now. I have been doing this primarily for weight control. I am basically a carnivore at heart, and don't eat much in the way of fruit or veggies. I take 1 tbsp of a homemade concoction of veggie powder per day consisting of kale, spinach, broccoli and blueberry. The veggie powder has only been for the last 5 years. Also. for the past 5 years, I intermittently fast eating only during a 7-hour daily window.

3. Supplements. Resveratrol for past 20-25 years. Started taking it during the first resveratrol craze. Small doses only then as it was quite expensive. Now 1g per day. Nicotinamide mononucleotide (NMN) or nicotinamide riboside. Been with this about 4 years as an anti-aging strategy as age is still the greatest risk factor for LOAD. Finally fish oil, CoQ10, Alpha Lipoic Acid, K2D3 combo, fisetin and quercetin (as senolytics), and turmeric.

4. Sleep. Doing everything in my power to get 8 actual hours of sleep per day. Results sometimes vary.

5. Work. I remain employed full-time with a percentage of that from home.

I have actual personal data that seems to indicate something is going right. In early 2023 I tried to enter the Lily Trailblazer ALZ-5 trial. Tested normal cogitatively, but was ultimately rejected as blood test was negative for p-tau. Then a few months later, I enrolled in the Ahead 3-45 study. Again got through all preliminary tests and took the amyloid PET scan. Result showed no amyloid. Doctor said I was lucky, and he would test me again in 7 years if I wanted. He could not explain why a (then 67-year) old APOE 4/4 had no amyloid beta. I do not have any of the "magic" genes that are highly protective, so I attribute my luck to the lifestyle factors. I wish I knew exactly which lifestyle variables were working in my specific case. If I had to guess, I would say the major factors are the lifetime of moderate exercise and the decades of occasional but strong keto dieting.

PS - The Ahead trial Doc said that even though I was amyloid free, I was still at very high risk later in life so should not regress to poor lifestyle choices.
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Re: talk about prevention strategies?

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Fiver wrote: Sun Apr 07, 2024 2:14 pm Anyone want to talk about prevention strategies?
The biggies for prevention that are typically cited are diet, exercise, sleep, reducing chronic stress and avoiding toxins. Although the devil is in the details. For example, there are folks who are convinced a carnivore diet is the only way to go, as there are folks just as convinced a low fat, vegan diet is imperative. I won't go into that, I'll just say I follow Dr Bredesen's advice for his Ketoflex diet as modified for ApoE4s as well as the other recommendations from his book, The End of Alzheimer's Program. I figure he's a neurologist who's researched neurodegenerative diseases for decades, who has written numerous peer-reviewed papers which cite ApoE4 specifically, he's married to an integrative physician, and has had success reversing cognitive decline with his protocol. I think that gives him his props and expertise with regard to ApoE4 peculiarities.

What I want to stress is something that is typically overlooked when discussing prevention strategies, following one's circadian rhythm. Yes, sleep is a subset of that, but it is so much more. Being out of sync with one’s circadian rhythms leads to multiple health issues, including Alzheimer's Disease. Disrupted circadian rhythm leads to cognitive deficits and that in turn feeds disrupted circadian rhythm which further feeds cell death, oxidative stress and amyloid deposition.
Circadian_rhythm_disruption.jpg
I'm traveling now and for the next few days, so I'm not able to take the time to elaborate, so I'm going to recommend reading the ApoE4.info wiki on Circadian Rhythm Circadian Rhythm
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Re: talk about prevention strategies?

Post by Plumster »

Oh are you a mouth breather too? :) Does taping work?
Yes, absolutely! About six years ago, just as I was entering menopause and my estrogen was dropping, I started having severe sleep problems and would wake up many times a night. I started myofunctional therapy and joined a breathing clinic, and learned I was tongue tied. The muscles in the tongue become weak with the drop in estrogen. I had functional frenuloplasty (oral surgery releasing my tongue). Boy did that make a difference immediately! I now tape nightly to ensure there's no more mouth breathing.
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