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There is some speculation on the latter article I posted for CVD and cancer. Though solely based on in-vitro/mechanistic evidence. If you want a longer read about a variety of hypothetical ways that Lithium can affect cancer, you can try: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954674/ Lithium in Cancer Therapy: Fruitful Friend or Fancy Foe? It also seems that there are a handful of rat/mice cancer-studies that resulted in benefits from Lithium. Take that as you like. There is some very superficial evidence in humans as well - but bordering on anecdotal.

https://karger.com/pps/article/93/1/36/893256/Mortality-and-Lithium-Protective-Effects-after Abstract Introduction: This study aimed to estimate all-cause mortality in patients after a first-episode mania (FEM) and examine whether six guideline-recommended medications can reduce mortality. Methods: The cohort included population-based FEM samples and matched controls from Taiwan, spanning 2007 to 2018. The primary outcomes assessed were all-cause/suicide-related mortality, while the secondary outcome focused on mortality associated with pharmacological treatments. We compared mortality in post-FEM patients and age-/sex-matched controls without any diagnosed bipolar disorders and patients with and without psychopharmacological treatment using Cox regression analysis, respectively. Statistics were presented with time-to-event adjusted hazard ratios (AHRs) and 95% confidence intervals (CIs). Results: The study included 54,092 post-FEM patients and 270,460 controls, totaling 2,467,417 person-years of follow-up. Post-FEM patients had higher risks of all-cause mortality (AHR 2.38, 95% CI: 2.31-2.45) and suicide death (10.80, 5.88-19.84) than controls. Lithium (0.62, 0.55-0.70), divalproex (0.89, 0.83-0.95), and aripiprazole (0.81, 0.66-1.00) were associated with reduced all-cause mortality compared to non-users. There were no significant all-cause mortality differences for quetiapine (0.95, 0.89-1.01), risperidone (0.92, 0.82-1.02), and paliperidone (1.24, 0.88-1.76) users. When accounting for drug action onset times in sensitivity analyses, only lithium significantly reduced all-cause mortality (AHR range 0.65-0.72). There were 35 and 16 suicide deaths in post-FEM patients and controls, respectively. No drug had a significant effect on suicide deaths (lithium: 6; divalproex: 7; aripiprazole: 0; quetiapine: 10; risperidone: 4; paliperidone: 1). Conclusion: Post-FEM patients had a higher risk of all-cause/suicide-related mortality, and lithium treatment might reduce all-cause mortality. Another, less interesting, study - comparing the effects of different BP drugs in a relatively short time after a first diagnosed BP-event. So too short to really affect chronic diseases. After excluding deaths in the first 3 weeks of treatment, only Lithium is associated with reduced mortality.

As a personal reference I'm adding one more study to my initial list of results: https://onlinelibrary.wiley.com/doi/abs/10.1111/acps.13519 Mood stabilizers and risk of all-cause, natural, and suicide mortality in bipolar disorder: A nationwide cohort study Abstract Objectives: People with bipolar disorder have an elevated risk of mortality. This study evaluated associations between the use of mood stabilizers and the risks of all-cause mortality, suicide, and natural mortality in a national cohort of people with bipolar disorder. Methods: In this nationwide cohort study, we used data from January 1, 2000, to December 31, 2016, collected from Taiwan's National Health Insurance Research Database and included 25,787 patients with bipolar disorder. Of these patients, 4000 died during the study period (including 760 and 2947 from suicide and natural causes, respectively). Each standardized mortality ratio (SMR) was calculated as the ratio of observed mortality in the bipolar cohort to the number of expected deaths in the general population. Multivariable Cox proportional hazards regression with a time-dependent model was performed to estimate the hazard ratio (HR) of each mood stabilizer with each mortality outcome. Results: The SMRs of all-cause mortality, suicide, and natural mortality in the bipolar disorder cohort were 5.26, 26.02, and 4.68, respectively. The use of mood stabilizers was significantly associated with decreased risks of all-cause mortality (adjusted HR [aHR] = 0.58, p< 0.001), suicide (aHR = 0.60, p < 0.001), and natural mortality (aHR = 0.55, p < 0.001) within a 5-year follow-up period after index admission. Among the individual mood stabilizers, lithium was associated with the lowest risks of all-cause mortality (aHR = 0.38, p < 0.001), suicide (aHR = 0.39, p < 0.001), and natural mortality (aHR = 0.37, p < 0.001). Conclusion: In addition to having protective effects against suicide and all-cause mortality, mood stabilizers also exert a substantial protective effect against natural mortality, with lithium associated with the lowest risk of mortality. In other words: Untreated bipolar patients had an increase in all-cause mortality - excluding suicide (what they call "natural mortality") - of +368% compared to the general population. This is not surprising: every epidemiological study confirms similar findings. The reason being: untreated Bipolar people make extremely bad life choices. Those bipolar patients treated with Lithium instead got a change in their "natural mortality rate" of -63% compared to the general population. Previously it was reported, that Lithium got a very large mortality advantage in BP patients compared to other BP drugs. This is the first study quantifying a mortality advantage compared to the general population. It is difficult to understand, that this is based on being a good mood stabilizer alone. In that case you would expect a normalization of the mortality rate to the population mean. Indeed it has been shown, that different BP medications are comparable on their effect on mood stability. Therefore the additional mortality benefits of Lithium compared to other mood stabilizers are likely based on direct biological effects on other causes of death. This is still only an epidemiological study. And unfortunately it's only the abstract. It would be very interesting to read up, what is the share of Lithium users among all treated BP patients in the sample. But it confirms similar findings in previous population studies - all pointing in the same direction.

I would agree in so far, as he is advocating some drugs - in particular ezetimibe - that simply do not have data supporting lower all-cause mortality or just CVD-mortality.... ....despite lowering LDL. LDL is a surrogate marker for a drug, it's not a replacement delivering actual data on survival. I find it actually a little frustrating, that Attia and Dayspring rightfully discuss studies on Niacin and fish oil at length, pointing out a lack of mortality benefit. And at the same time talking about ezetimibe without doing the same and just recommend it to their listeners. To be clear: there is no study among the dozen or so on ezetimibe, that shows lower all cause mortality or just CVD mortality. The Chinese study you just cited is of course a cohort study, not an RCT. As there are a ton of factors that influence LDL/ApoB (including taking a statin BECAUSE of a previous CVD event), these are difficult to interpret.

A cautionary tale of bempedoic acid - an LDL drug for those that can't take these horrible, horrible (did I mention horrible?) statins: https://sensiblemed.substack.com/p/lipid-lowering-a-bempedoic-acid-subset It is always important to ask, if all-cause mortality is moving in the correct direction. A drug that lowers CVD and CVD mortality - but does not affect all-cause mortality - is very suspect. It's a sign of some serious side effects going on. Statins - despite being horrible, horrible drugs - have data backing up lower all-cause mortality for the at-risk patients assigned to them in the clinical studies. BA instead appears to be in the same camp as ezetimibe; both lowering LDL and CVD incidence - but having no benefit for mortality and lifespan for people at risk for CVD.

I'm sorry - but did you, Ron and Todd, even read that article past the abstract? The article does not deliver what it claims in the abstract. The only article cited that makes any statement to that claim is: https://www.tandfonline.com/doi/abs/10.1586/17512433.2015.1011125?journalCode=ierj20 It's an article by THE SAME AUTHORS. It's not a trial. It's not an analysis of an RCT or association study. It's purely in-vitro science - mechanistic evidence. Generally these authors love to cite themselves to "prove" their strongest claims. But none of their self-references contain an analysis of clinical trials - it's all mechanistic evidence. Their claim that none of the statin trials after 2004 showed a benefit in outcomes or mortality is just plain wrong. JUPITER (2008) and HOPE-3 (2016) were 2 major statin trials for Rosuvastatin and showed that early and aggressive LDL-lowering has a propotional benefit in lowering all-cause mortality and events. Their only trial data that they try to spin as evidence against statins is from cohort studies. But as there are a range of factors that influence LDL (diet; sickness; genetics; LDL-medication because of prior heart attacks etc.) that's just not good data to proof anything about LDL - e.g. these studies almost never correct for pre-existing conditions. In summary: this article is highly misleading - the claim in the abstract is almost a lie; depending how generous you are with your goodwill.

It seems Lithium can even be protective for the kidneys at sub-therapeutic dosing. Researchers in a post-hoc study in humans found, that people taking therapeutic dosing of lithium for 20 years had somewhat better kidney function than bipolar folks using different medication (note: lithium is supposed to be the therapy that puts kidneys at risk - not the other way around) https://news.utoledo.edu/index.php/04_11_2022/low-dose-lithium-may-slow-kidney-aging-utoledo-study-finds https://www.jci.org/articles/view/141848 They also found, that mice treated with a dose-equivalent of about 1/3 the therapeutic dose in humans (so: sub-therapeutic as in the placebo dementia studies) had a substantially better preserved kidney function during aging. Just like humans, mice loose about 50% of their kidney function until old age. But much less so with an intermediate lithium dose, comparable to sub-therapeutic dosing in humans. So it may be, that yes - lithium at therapeutic doses can cause toxicity in the kidneys for vulnerable patients, if used over years. At the same time it also exerts a protective effect. This protective effect might already be present at sub-therapeutic dosing, where the toxic effects are much less of a concern. Edit: To be extremely on point - that is NOT A FREE PASS to use sub-therapeutic lithium without any concerns. If you're taking 150 mg or 300 mg of Lithium carbonate you absolutely have to do blood tests for: - lithium levels achieved - kidney function - thyroid function Lithium DOES INTERACT WITH OTHER MEDICATION. In particular common stuff like blood pressure medication and pain killers. Therefore, if you start lithium, every doctor will tell you to MEASURE the parameters just mentioned one week after starting a new dose of lithium. And subsequently at least annually.

Again - there is essentially no effective treatment for Alzheimer's and other types for dementia. The 2 new anti-body therapies would hardly count as effective for clinical outcomes in almost any other field of medicine. And they demonstrate far worse side-effects than is documented for sub-therapeutic or low-range therapeutic dosing of lithium. In Alduhelm, side effects are almost a feature, with 40% of patients diagnosed with either brain bleeding or brain swelling. Serious lithium problems generally build-up over time, particularly with lower doses, and can be easily identified in bi-annually blood work. In addition there is data of patients using lithium for decades, and at up to 10 times higher dosing than the small placebo trial in lithium. They're doing fine in comparison - the drastically lower all-cause mortality compared to mood-disorder patients using other medications was also found in 2 studies on population data in Finland and Taiwan. In fact, I'm puzzled about the lack of reporting about the favorable data situation regarding lithium and dementia. Even dedicated Alzheimer's advocacy societies hardly report about it (according to a google site-search of their webpages). None of the major English-language Alzheimer sites seem to report the small placebo trial. Most also don't report the recent epidemiological study of bipolar patients on lithium vs. general population. Instead some rat study from 2 years ago seems to be weirdly popular on alzheimer's webpages that report about lithium at all. Which is all very odd, given the dire situation for any medical treatments for dementia. The anti-body trials easily receive 100 times that coverage - well, infinite for the dementia societies that don't report about lithium at all. Despite the overall data situation for lithium being much more promising. Importantly, there is no null finding. So far: - there is comprehensive population data from even 20 years ago showing much lower dementia in bipolar lithium users vs. bipolar non-lithium users - an association for dementia and ground-water lithium levels in studies from Denmark and Texas; it's a pretty weak effect (not so much lithium) - but statistically significant - the recent study comparing bipolar people on lithium with the general population in a UK-cohort (strong association in favor of lithium) - 2 pre-clinical trials over 12 weeks and 15 weeks, showing favorable effects on dementia bio-markers - 2 small placebo controlled trials over a couple of years; both showing much (really: MUCH) better effect than the 2 recent anti-body drugs; albeit not quite statistically significant ...and then there is the ongoing replication trial - LATTICE - powered to achieve full statistical significance. Given the dire situation on the Alzheimer's/dementia front, you might assume that lithium would get some attention. Maybe not on Reddit or other social media. But at least among dedicated advocacy and research societies. Some of whom seem to not report it at all - in particular not the placebo controlled trials.

Yes, as used in therapeutic dosing for mood-disorders - that is about 170 mg to 340 mg of elemental lithium per day - there is a requirement for regular monitoring for lithium levels and kidney blood parameters. Just to be clear: most people in this therapeutic range do not develop any problems with their kidneys. Nonetheless, it would be foolish to take such a high dose without close monitoring of blood parameters. More interesting would be the question of sub-therapeutic dosing, such as in the small trial in patients with mild cognitive impairment - so 28 mg to 112 mg of elemental lithium per day. We know that the 5 mg of lithium typical used as a supplement is probably very safe, unless you are a special case. So what about 28 mg (sub-therapeutical) instead of 170 mg for bipolar disorder (Swanson's even offers 20 mg in pill as supplement)? Unfortunately I'm not able to find studies on side-effect for this "intermediate" dosing regimen. However, so far it seems okay in term of effectiveness and side effects (provided regular monitoring of blood markers), compared to the alternative drugs - if the results are confirmed in the LATTICE trial. Because alternative drugs do not really work. Aducanumab is the only approved drug that showed some effectiveness: https://www.nytimes.com/2021/06/07/health/aduhelm-fda-alzheimers-drug.html There were 2 trials. One trial showed no effect. The other trial showed a delay in progression of 22% over 18 month; that is the intervention group takes about 22% more time to have the same level of Alzheimers progression (4 month over 18 month). Note: that's a different metric as the Alzheimer's conversion rate in the small lithium trial. The intervention group in lithium didn't reach the 13-month dementia conversion level of the placebo group even after 40 months (still being well above that level). In the same metric as in the Aducanumab trial that would be more than 200% delay in progression. Also lithium isn't billed as 56.000 USD per year and doesn't cause brain swelling/bleeding (in unisono with headaches, nausea and fainting) as a side effect in 40% of the patients. If I would be diagnosed with mild cognitive impairment, I sure as hell would try out lithium at 150 mg lithium carbonate (28 mg elemental lithium) and combination with some regular blood test. And provided that serious side effects are sufficiently rare, I would think about it even now. Also note: mood-disorder people taking therapeutic dosing had a 72% reduced all-cause mortality compared to carefully matched mood disorder people using different drugs, after 12 years of epidemiological observation. Just to put into perspective the dangers of a high dose regimen. At the very least that tells you how shitty the alternative drugs for mood disorder are. Of course, these lithium users have regular checks on their kidney function. That's a smart idea for any dose that goes substantially above the 5 mg supplement level.

...no I'm not talking about electric cars. But there have been some intriguing recent findings for taking lithium at clinical dosing to prevent dementia and maybe even lower mortality. Let's talk about that. It all started quite a while ago with findings, that geographical areas in Asia, Europe and the US with higher lithium content in drinking water had a notably lower rate of suicide and a somewhat lower rate in all-cause mortality (i.e. not impressive at all). That was a curious finding, that lead people like Peter Attia or Michael Rae to supplement with that - it's nowadays actually fairly common in the "longevity" community to take a pill containing 5 mg of elemental lithium a day. That's above food/water intake in lithium rich areas. We gonna talk about dosing in a moment and I'm linking an informative video at the end of this post. Researchers try to tease out the effect of lithium in cohort studies... because there is a group of people that take high dose lithium (900 mg up to 1800 mg lithium carbonate a day - that could be lethal dosing if you're no careful) for decades: folks with mood conditions such as bipolar disorder or severe depression. That's an obvious confounder - this population has a higher all-cause mortality. Not just by accidental deaths. Anything from cancer to cardiovascular disease - all related to sub-optimal lifestyle choices. They tend to eat more, exercise less, are heavier smokers and drug abusers. So take the following epidemiological studies with a big salt crystal, mined deep in the mountains of some alpine range. A recent epidemiological study on dementia in lithium users found a 44% reduction in dementia comparing lithium users (that is: people affected by mood disorders) vs. the non-users in the general population - after adjusting for a common set of confounders: https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003941 This is essentially a follow up on a number of smaller or less sophisticated studies in the previous 20 years, finding lower levels of dementia in bipolar people using lithium vs. bipolar people using other kinds of medication. The recent result is interesting insofar, as mood disorders increase the risk of dementia. It's still not controlled study - and given the particularities of lithium users, there might some relevant confounders not covered in the common set of variables. Curiously, a small randomized trial in people with mild cognitive impairment found a similar risk ratio. These folks didn't have mood disorders - but are at risk for Alzheimer's. Dosing ranged between 150 mg and 600 mg a day of lithium carbonate (18,8 mg of elemental lithium per 100 mg LiC), targeting a certain blood level. Substantially above "natural" exposure and common supplements - but also lower than therapeutic levels in mood disorders: https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/clinical-and-biological-effects-of-longterm-lithium-treatment-in-older-adults-with-amnestic-mild-cognitive-impairment-randomised-clinical-trial/EF9931A98FFD7FA99F2202C19063EF77 As a result, there is a 47% reduction in progression from MCI to dementia - backed up by bio-markers for dementia and cognitive testing: However - due to the small scale of the trial, the result wasn't quite statistical significant; a p-value of 0,06 instead of the commonly used metric of 0,05 or below. To resolve any doubts about that, a research group in Pittsburgh started a replication the trial - the LATTICE-trial - to achieve results to full statistical significance: https://lldep.pitt.edu/projects-2/lattice/ The trial is probably going to publish it's main findings by the end of 2024. Another very curious finding, and the immediate cause for this write up, is another epidemiological study published early this year (2023), based on data off the UK Biobank: https://www.aging-us.com/article/204476/text They are comparing people with mood-disorders using lithium alone or in combination with other drugs to mood-disorder affected people using other drugs, but not lithium. They create both sample groups with carefully matched demographic parameters - made possible by the over 500.000 participants in the UK Biobank. At the outset they're essentially the same - just differing in using lithium as a treatment or not. Follow-up time is 12 years. The result is really stupid (meaning: almost unbelievable): a 72,6% reduction in all-cause mortality. After excluding any accidental deaths (as lithium is effective against suicide)and any early deaths. All causes of death seem to be heavily affected in favor of lithium, from cancer to cardiovascular. Now that's still not a controlled trial. That's still based on a general group with higher baseline-mortality. And unfortunately the authors are not calculating a direct mortality curve comparison between lithium users and the non-mood-disorder population in the database. Though examining the mortality curve for all mood-disorder affected people vs. non-affected people reveals, that the increase in mortality is not dramatic. So lithium using mood-disorder affected people almost certainly rank better for all-cause mortality than the general population. Also, importantly, this is not the censoring effect of metformin. Metformin users in 2 important epidemiological studies performed ever so slightly better than non-users - despite the users being (pre-)diabetic. The problem: metformin is the first line drug for every early diabetic patient. And in these studies, every person adding another drug to metformin, because their diabetes got worse, was exluded from the group of metformin users (despite still taking metformin). So it compared only the self-selected best performing (pre-)diabetics who due to lifestyle changes didn't progress, with the general population. Best performing pre-Diabetics, that in addition got much more frequent medical check-ups than the general population. Lithium is NOT a first line drug - because of the need for close monitoring of lithium levels. Also in this study ANY lithium intake counted as taking lithium - no censoring or self-selection of the sample. Finally, it bears repeating that we are not talking about that weak-ass "longevity" lithium dosing of 5 mg a day in the recent studies just presented. To make that point and give a detailed insight into the different dosing regimens, I highly recommend this youtube video: Now... I'm mostly doing this superficial summary to have a post that I can reference for my own purposes later. Nonetheless: let's discuss!

As a complete layman in AI, I wonder, if the alignment problem will only matter, if weapon systems will be under control of autonomous or networked agent driven AI systems. Simply put: as long as the government retains full control of the military and weaponized law enforcement (from FBI to the TSA), it has the power to shut down server farms, the internet, and seize control of every "hard factor" that any AI system may wish to take over. That only leaves indirect means of control, that AI can try to pursue, i.e. posing as helpful to humans, so that they voluntarily deploy AI systems. That is: it will only survive if it is providing a benefit. Any attempt at directly harming humans or takeover infrastructure in a way that openly causes damage, can be easily countered by the government having control of the weapons in the hands of the law and military. The government can order to shut down the internet - by force if necessary (as you can see in quite a number of third world countries during "elections" and protests). The government can direct companies to do their biding - by force if necessary. Now, AI may try to blackmail politicians not to exercise the power of government. But that only goes so far. As long as the military doesn't allow networked AI controlled systems and law enforcement is done by humans only, there is always the risk that AI will get shutdown after the next election (and a new bunch a politicians where blackmail might not work) if it's posing as harmful. For the opposite, see the great 1970s movie Colossus - using nuclear blackmail, AI takes over the world and orders the execution of opposing scientists:

@ Saul: I guess this is hard to come to conclusion about without putting some numbers to it. What is a good lipid level? Conventional wisdom for people in primary prevention would say that anything below 100 mg/dl in LDL-C is "good". However, people like Peter Attia, Tom Dayspring and Allan Sniderman (the latter 2 are very well respected researchers, who almost single handily shaped the modern view on blood lipids over the past 40 years) make a reasonable point, that anyone is at high risk for ASCVD if someone is living long enough. See the graph from the CDC that I posted earlier. There is good data out off large randomized placebo controlled clinical trials and genetic cohort studies demonstrating, that APO-B/LDL-C levels substantially below 100mg/dl confer additional benefit for cardiovascular mortality and all-cause mortality. Up to a point where the progress of ASCVD can be virtually stopped. How to get to those low levels is someones personal journey. But drugs can reasonably play a part in that. It is prudent to be skeptical about a particular drug, of course. Even among the same class of drugs, there can be large variations. Alirocumab has much more convincing data than the other PCSK9-inhibitor on the market - Evolocumab. The first fibrates increased mortality - whereas modern fibrates do the opposite. There was a statin called Lipobay in the early 2000s that had 20-80 times the rate of serious side effects than it's competitors - Bayer Pharma deceived the public about that, got sued for billions and had to pull it from the market. And ezetimibe has no effect on mortality, not even cardiovascular, despite lowering LDL - which can make you question what kind of long-term side effects lurk in the background. But don't throw out the baby with the bathwater. Modern statins - particularly the high-potency ones Atorvastatin and Rosuvastatin - have long term data showing decreased all-cause mortality. And in proportion to the level of LDL-lowering. We are talking about 5 years of clinical trials and up to 15 years of well collected follow-up data, i.e. 20 years of total observation. So if Alirocumab is not possible to acquire and you prefer to not spend your days and nights on the toilet thanks to bile acid drugs - statins are an option that can be considered. @ Ron Put: That study is certainly not up to date. Just last year a major review in the UK found, that the diabetes risk of statins is negligible if you compare it with the ASCVD-benefit of statins. That's the reason diabetic patients routinely get statin prescriptions as part of their treatment.

To supplement my comment - here are the results of the most recent meta analysis of the effects of ezetimibe and PCSK9 inhibitors: https://hospitalhealthcare.com/clinical/cardiovascular/meta-analysis-finds-pcsk9-inhibitors-and-ezetimibe-combined-with-statins-reduce-non-fatal-mi-and-stroke-in-high-risk-patients-but-not-death/ and the underlying study in the BMJ: https://boris.unibe.ch/169782/1/bmj-2021-069116.full.pdf Ezetimibie cannot be universally recommended. The data on mortality (cardiovascular or all-cause) is pretty clear: there is no benefit. Note: this is also true comparing patients taking ezetimibe monotherapy vs. placebo patients taking nothing else - i.e. not even statins. Why is there no benefit? We don't really know, as there hasn't been sufficient collection of data by the drug maker. It could be, that it's simply too weak an effect. Or it could be negative side effects that increase the risk of ASCVD or some other cause of death through some other mechanisms. PSCK9 inhibitors are a little more complicated. Evolocumab has confusing data on mortality at best. Alirocumab on the other hand got data for a clear benefit on all-cause mortality. As the meta analysis is combining both drugs, the net result is "no benefit" for mortality in their study. Interestingly Peter Attia commented as to injecting Alirocumab. That leaves statins, fibrates and bile acid sequestrians. Of which statins by far have the best data for effects and least side effects. This is not to say that they don't have side effects. Just that lowering you LDL by 50 mg using statins is much easier and a much more pleasant experience than trying the same with fibrates and bile acid drugs.

That's the distribution of causes of death by age group in the US (from the cdc): Given it's enormous share in causes of death among the (very) old, it seems reasonable to emphasize prevention. It's not just about longevity, but also quality of life - which tends to take a sharp downturn with advanced ASCVD (certainly after your first hearth attack or stroke). The current data-situation supports the notion, that very low levels of APOB-bearing particles will stop the progression of ASCVD - or even reverse it (albeit very slowly). Now how aggressive you'll need to be depends on your personal risk. However, advanced age generally is the most prevalent risk. So there is a point to try to lower "elevated" APOB by medical means if necessary, if you're older than, say, 50. Where "elevated" could mean anything above 60/70 mg/dl. However, not all drugs are the same. For example ezetimibe/zetia is successful in lowering LDL/APOB - but no study was able to find an effect on mortality. This could be a hint, that there are unaccounted for side effects. That not a new thing: the first fibrates on the market where hailed for lowering LDL. But long-term analysis demonstrated that they increased mortality. And there is indeed a large-scale ex-post cohort analysis in South Korea, that shows increased mortality with ezetimibe, Long story short: you only should consider LDL-lowering drugs, that are proven to lower all-cause mortality. Statins - for better or worse - are part of that category. And for the vast majority of people they are the best option, because PCSK9-inhibitors are damn expensive and require a doctors consultation every 14 days. Also one of the 2 inhibitors on the market has somewhat unclear data on all-cause mortality.

You have to remember that we're talking about a living being - e.g. a fly, mouse, human. That's not some change in a computer code, that you can arrange in a second, run for an hour and observe the outcome. Even in-vitro studies (cells in a dish) take weeks to figure out what and how to target, execute and analyze. Ideally! In practice it can be months. AI can help, sure - but we will need a much better lab-robots to really speed up this process. That still doesn't address the challenge, that interactions between cells/tissues in a living being are decisive - i.e. most in-vitro results don't translate even to the mice/rat stage. And doing experiments in animals of that kind will take months for every individual "fuzzy"-change. And there is an in-credible number of changes. Systematically probing even 10% of what we don't know will eat up the entire US government budget. In mice! Most things that somewhat work in mice fail in the next step: human clinical trials. And you are not proposing, to find 100 Million volunteers to test out the most basic areas of missing knowledge - a lot of which will require genetic engineering which can realistically only be done at the embryo stage and thus requires to wait 9 month to see the effect on a living, independent being. There is project currently under development, to create a "worm bot", that can assess in an industrial manner the effect of drugs on c.elegans (a tiny worm in a dish). This is based on the assumption, that there can be some lessons learned from that simple organisms in-vivo. The analysis of the mechanisms, once there is a success on lifespan, still needs to be done by hand (they only look at, if a drug increases lifespan - no real bio-analysis on the impact on metabolism). But again: even mice result mostly don't translate to humans. I leave it to you to assess the value of doing pre-screening in tiny worms. Also we are not even close to anywhere near 100%. Just by looking at the number of proteins transcribed in a cell that we have no real clue where and what they end up doing we are heavily outmatched. And we are still discovering fundamental processes about the inner workings of the cell and interaction between cells, that we didn't know 10 years ago to be fundamental processes controlling the metabolism! We still don't know much about extra-cellular vesicles or O-GlcNAcylation - just that there is a lot of it going on steering fundamental processes of the cell. Why? Where? Regulating mechanisms? Very incomplete at best. You are saying: maybe AI is so smart, that it just knows what to do, even with gigantic gaps about the fundamental workings of the cell. Than make that argument, please. Just making that statement is not an argument. This needs to be an argument about to what extend information is required to make somewhat accurate predictions about a complex system - even assuming 1 million times scaling of current AI levels (whatever that means). I'm not into mathematical theorems, so I can't guide you in making that argument. But unless this argument can be made, everything about AI being a game changer in biomedical science is pure speculation. As it stands AI can't solve our fundamental problems about what kind of string theory - if any at all - is the correct model of our universe. There just isn't sufficient empirical data about the fundamental workings of our universe available. The same is true for human metabolism - though at least in theory the missing information can be gathered.