Also worth mentioning ACE inhibitors didn’t show lower risk of death in the 2024 UK Biobank data and actually showed a (slightly) faster risk. I see no reason for anyone to use an ACEi over an ARB.
“As our findings suggested that there may be a drug class effect on mortality, we performed a pooled analysis, combining drugs from the same class (Methods). We selected Statins, PDE5i, Estrogens, given that we observed some positive effect on survival for some of these drugs. We added SGLTi, and Metformin, due to previous reports of positive effect, and ACEi due to potential reports of positive effects (Figure 5, Data Table 5). Statins (HR 0.97, Cl 0.94-1.00) and Estrogen (HR 0.76, Cl 0.67-0.85), as a class, reduced mortality, so did SGLT2i (HR 0.64, Cl 0.45-0.89), although with a much lower sample size. Metformin (HR 1.01, Cl 0.95-1.07) had a neutral effect on mortality, while ACEi (HR 1.11, Cl 1.06-1.15) was associated with increased mortality.”
I am currently taking 120 mg daily, but I am going to step up to 1 gram. The reason I am not taking 1 gram now is that it involves too many pills and becomes expensive at that level. Filling your own capsules is a good alternative. I have just been too lazy of late to fill my 000 empty capsules with pure melatonin that I have on hand.
High-dose melatonin is something you have to take on a leap of faith, much like rapamycin.
I have been taking high doses of melatonin since circa 1985
You can find many books and YouTube videos pro and con.
I am certainly not recommending the doses I take to anyone else.
Neuroprotection
The brain is highly susceptible to oxidative damage, and melatonin’s protective effects are being actively investigated for neurodegenerative conditions.
Combating Neurodegeneration: In experimental models of Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s (HD) disease, melatonin has been shown to effectively prevent mitochondrial dysfunction and neuronal damage. The doses required for this neuroprotection are thought to be 2–3 orders of magnitude higher than those needed for sleep regulation.
Future Clinical Trials: Given the promising preclinical evidence, experts suggest that clinical trials using high doses of 50–100 mg/day are needed to fully assess melatonin’s therapeutic potential in these devastating disorders.
