What are those 6 items? @DrFraser
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Rapamycin
Empagliflozin or Dapagliflozin
Telmisartan at least 80 mg
Amlodipine
Optimizing Vitamin D, Testosterone/Estrogen (both genders) and Omega 3 Index
Atorvastatin (more controversial)
Low dose GLP-1/GIP
Tadalafil 5 mg daily
Lithium currently 5 mg twice daily of the orotate
Actually 11 items ⌠each of which independently looks sensible for longevity.
Lifestyle is huge also ⌠diet Iâm good, sleep getting managed better and monitored with Oura, exercise need a bit more, stress ⌠hmm working on it.
Keeping the brain busy ⌠Yes - work 7 days a week, including at least 15 hours per week of reading medical literature.
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What about Melatonin?
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I guess the evidence is not there -Alzheimerâs Society (UK) states âEvidence so far suggests melatonin does not affect risk of dementia.â For PD there may be some evidence ⌠but for my concern on having ApoE3/E4 I donât see a role for it currently.
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This question never occurred to me until seeing your listâŚ.
Since starting rapa, my glucose spikes are proving hard to controlâŚ
GLP 1âs have not occurred to me because I am not overweight. Do you feel micro dosing it might be something to consider? I worry about the side effects but perhaps with low doses itâs not a concern?
@John_Hemming Im back on the melatonin train. Sunshine, supplementation, protecting my own melatonin production (light hygiene). Regarding PD/AD, Dr Loh says to watch out for alcohol induced (via hepciden) iron overload in the brain
In her latest podcast.
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@DrFraser Which of these interventions deals with iron overload in brain tissues? Or is avoiding iron overload through diet and alcohol enough? Blood donations?
Rapamycin does as it seems to decrease iron absorption via increasing Hepcidin. I think the other issue is monitoring ferritin and transferrin saturation and if elevated - important to either donate or chelate (donation would be preferred as it benefits someone else and is free).
Just like with Joints â the Brain when iron gets in - it doesnât leave even when you donate blood and your ferritin comes down. It continues to sit there and add to oxidative stress. So on an ongoing basis - donât let iron overload go untreated (or undiagnosed).
@Beth If you donât have weight to lose - then using one of the older GLPs would be preferred like Trulicity (Dulaglutide) or Byetta (Exenatide) which have the benefit of crossing the BBB which Semaglutide and Tirzepatide donât. We donât know if that is the active ingredient in Neurocognitive decline â and there is mounting evidence with PD that they benefit and strong association with decreased risk of AD with all GLP1âs. So I see these as great longevity medications. The issue with the older agents is they arenât being compounded - so cost = get them out of Canada (way cheaper but need an Rx) or sort out other off shore options - otherwise youâll be into $1200/month if U.S. based.
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I would be interested to see the detailed research on melatonin. The mistake made by many researchers is to ignore (or be unaware of) the fact that melatonin concentration levels in CSF are multiples of that in blood serum. The CSF passes into the brain when blood pressure goes down as people sleep. This provides high levels (higher than serum) of melatonin to neurons.
Realistically the dosing of melatonin that is often used wonât really provide that much of an increase in the endogenous melatonin - to the brain.
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From the article:
âRecent studies have also documented that a variety of food stuffs, e.g., vegetables, cereals, fruits, nuts, seeds, grapes, red wine and beer contain considerable amounts of melatoninâ
I was totally unaware of this.
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SGLT2i might reduce iron overload.
But otherwise itâs so complex⌠Some people are also looking at lactoferrin for AD and longevity.
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Weâll look at that! Looks like my melatonin supply is assured.
Beer and red wine are 2 of my 3 main food groups! (The other being vodka, of course.)
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Melatonin is a substance where there is no money in promoting it. So people donât.
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Careful, youâll wake up Hatchet Granny.
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I have never seen any evidence of iron levels in the brain not dropping if ferritin levels drop a lot, and that doesnât make sense to me. Do you have any references for this claim?
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Really good and valid question. I think the issue is little evidence of improvement with phlebotomy and even with chelation - the levels come down - but the neurodegeneration doesnât seem to improve.
It is really difficult to find references on this - this one in the conclusion speaks to this a bit.
It looks as though you can slowly remove with chelation that crosses the BBB, but not seeing much showing this with phlebotomy. But unfortunately, once symptomatic - just like with joint involvement - doesnât reverse with resolution of the iron levels.
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Thanks for the link to the paper. Here are some quotes from the paper:
" Aging processes lead to an increase in the amount of iron in brain tissue. This physiological process could compromise the iron homeostatic system [51], leading to an excess of iron that is not efficiently chelated by iron proteins."
âIn agreement, recently, the treatment of four NF patients with the BBB permeable iron-chelator deferiprone (DFP) resulted in a positive clinical outcome [106]. In one case, the authors were able to revert symptoms after a few months of treatment, showing that the earlier the treatment was initiated, the better the results on disease progression were.â
âGiven that the iron chelator does not modify the diseases suggests the noncausal role of iron in most neurodegenerative diseases, but it should be kept in mind that the iron accumulation process is very slow, and when it becomes evident, neuronal death has already occurred. Therefore, treatment with chelators is performed when the damage is already severe and difficult to recover. An alternative explanation for the limited success of chelation therapies can be ascribed to the involvement of multiple iron roles: iron assumes a crucial role not only in neurotransmitter synthesis, primarily dopamine, but also in synaptic plasticity. Disrupting concurrently these two pathways, it is not surprising that improvements are not observed, but rather cognitive deterioration occurs.â
What they say above suggests to me that chelation therapy doesnât work in neurodegenerative diseases, not necessarily because the chelation therapy doesnât reduce brain iron but because the damage resulting from the excess iron is already done and wonât be reversed by reducing iron levels. That said, I donât see them claim that chelation therapy effectively removes brain iron, so they donât rule out the possibility that difficulty in chelating iron from the brain is a problem. In fact, in the first quote above, they claim that excess brain iron may not be easily chelatd by iron proteins. What they mean by âiron proteinsâ here is not clear but checking reference 51 (PMID: 12208347) They appear to be talking about lipofuscin.
Lipofuscin is well known to accumulate in cells with aging and while lipofuscin is not inherently an iron containing material, it does bind to iron and the bound iron results in oxidative stress. Since lipofuscin is not easily removed by the body, perhaps when they refer to brain iron not being easily chelated they are talking about accumuluation of lipofuscin and the iron that gets bound to it. That would make senses to me. In that case, the lipofuscin accumulation probably depends in part on cumulative exposure to excess iron so people that have excessive iron for extended periods of time, may have increased levels of lipofuscin (and consequently iron bound to lipofuscin) in their brains, and this is not reversible by chelation but can merely be slowed down by chelation.
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"In brains of creatine-treated mice, there was a trend toward a reduction of reactive oxygen species and significantly lower accumulation of the âaging pigmentâ lipofuscin. "
Creatine might reduce lipofucin build up?
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