I will test this out. There is no reason why it should be a prescription drug as it is in food anyway. Salmon has quite a bit.
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The once a week dosing may be because it is more powerful. I have bought the one available in the UK and will compare this to dedrogyl.
My weekly blood tests which monitor amongst other things D3 will make comparing effects quite easy.
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Beth
#184
Excellent find for me because this one is vegan! I see they ship to the US, but it will be costly, so I’ll just stock up
If anyone in the US is interested, I’m happy to place a larger order and then I can send it to you (you can just pay shipping from me to you). Just let me know.
EDIT: incase anyone is interested, I just ordered this and it’s shipping from Michigan. On sale for $17 for 60 pills, 2000iu, free shipping on orders over $48.
AnUser
#185
What are the differences with D3 on RCT’s or EPI for outcomes, safety, etc?
Omega-3 and Vit D together seem to be most helpful for slowing aging.
Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial.
Bischoff-Ferrari HA, Gängler S, Wieczorek M, Belsky DW, Ryan J, Kressig RW, Stähelin HB, Theiler R, Dawson-Hughes B, Rizzoli R, Vellas B, Rouch L, Guyonnet S, Egli A, Orav EJ, Willett W, **Horvath S.**Nat Aging. 2025 Feb 3. doi: 10.1038/s43587-024-00793-y. Online ahead of print. PMID: 39900648 Open Access
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adssx
#187
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cl-user
#188
I just posted a new paper about tadalafil for dementia prevention in the tadalafil thread.
The adjusted odd ratio for dementia is 0.68 (0.59, 0.78) in the ED cohort and a very impressive 0.45 (0.39,0.53) for the lower urinary tract symptom cohort.
Maybe the second cohort is more representative of the people taking tadalafil for longevity rather than ED.
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Josh
#189
Do they adjust this for depression or being in a relationship or loneliness or satisfaction in life or anything? All of those could be a big factor.
Grok points out that people taking prescriptions are more likely to regularly visit a doctor, have insurance, and take what the doctor prescribes, beyond normal education/activity/income variance. Hypertension and lipids is a big factor, and maybe these are under better control?
“Tadalafil is associated with significantly more cardiovascular benefits compared to sildenafil in erectile dysfunction patients.”
Above confounders should not apply to directly comparing tadalafil with sildenafil, and greater heart benefits on the one with longer half life probably means it actually is effective. If similar mechanism helps dementia we should also see a stronger benefit there?
EDIT: It looks like tadalafil also was more effective for dementia but within error bars. Posted further analysis in other thread.
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cl-user
#190
I’ve updated the post with the results for the lower urinary tract symptom cohort. Presumably these were not people taking it for ED.
BTW these are massive cohorts: The final cohort included 509,788 men with erectile dysfunction and 1,075,908 with lower urinary tract symptoms.
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Thank you for this article. I’ve added it to my database.
Some prior articles seemed to indicate sildenafil was superior in this regard. However, this makes less sense to me, given the very short half life. Daily 5 mg tadalafil is my preferred to have sustained levels 24/7.
I’m glad this review had the outcomes listed. I’d really like them to continue on for longer than just 3 years.
Ultimately, the best study will be picking folks with ApoE4/E4 who are getting to the age where we think they are starting to risk mild cognitive impairment, and have a treatment with “Substance X” which could be a polypill of Rapamycin/Tadalafil/Lithium/SGLT-2 for example and track them with the controls for declines on their Montreal Cognitive Assessment (MOCA).
One of the things I’m looking for, and haven’t been able to find is good data on the typical trajectory of individuals with ApoE4/E4 who have MCI and their average decline in MOCA over time. In this fashion, one could eliminate the need for a control group to some extent - as no one would want to be in the control group. If anyone has this data, I’d appreciate the source.
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I haven’t had a chance to read through the article, but this might be of interest as an overview of plasmalogens related to dementia and ApoE4
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medaura
#193
I’ve read the research on plasmalogens for apoE4 carriers and based on that research have been supplementing with it. It does seem to bring a certain edge to my mind though not sure if it’s placebo. Some other research I’ve delved into suggests that supplementation might not be effective at raising brain levels. It’s a pretty expensive supplement but because it SEEMS to be doing something I keep taking it.
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Here is some related data.
Li W , Qiu Q , Sun L , Li X , Xiao S . Short-term adverse effects of the apolipoprotein E ε4 allele over language function and executive function in healthy older adults. Neuropsychiatr Dis Treat . 2019;15:1855-1861. doi:10.2147/NDT.S183064
and
Skylar Walters et al, Associations of Sex, Race, and Apolipoprotein E Alleles With Multiple Domains of Cognition Among Older Adults, JAMA Neurology (2023). DOI: 10.1001/jamaneurol.2023.2169
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Josh
#195
Bryan Johnson said he was trying plasmalogens but i never saw update if it helped any markers or discontinued.
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medaura
#196
I don’t know how it could help any markers he can measure unless he tracks things like working memory, reaction times etc. When it comes to cognition, I put a lot more trust in subjective evaluations.
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Josh
#197
Prodome has a test that measure serum blood levels of a lot of adjacent things like various kinds of lipids and plasmalogens. So you can at least verify it’s getting absorbed… It’s not hard to measure reaction times or you can go more invasive and measure spinal fluid levels etc.
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Innovations in noninvasive sensory stimulation treatments to combat Alzheimer’s disease
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adssx
#199
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Can you repost your updated current protocol?
@DrFraser this may be of interest.
There are a few theories on what contributes to and causes AD. The Tau thing, genetics, and oral microbiome. One microbe of interest is Porphyromonas gingivalis
The oral microbiome is getting a lot of attention and a “new” drug is now in Phase II/III trials.
The GAIN trial (NCT03823404) is a Phase II/III double-blind, placebo-controlled clinical trial evaluating the safety and clinical activity of atuzaginstat (COR388), a novel bacterial virulence inhibitor, in patients with mild-moderate Alzheimer’s disease (AD).
COR388 is not super new, I’ve found research on this going back to 2017 and it is available as a research chemical.
Here is a good article on this
More importantly, the study explains the theory, results and how it all ties into the APOE effects related to Porphyromonas gingivalis
Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors
https://www.science.org/doi/10.1126/sciadv.aau3333
Now I need to read the protocol used in the study and see what the dosing is and check into getting some Atuzaginstat/COR388.
From my quick review on the weekend, it seems to me that early use of this drug should be tremendously beneficial not only for AD but also for CVD.
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