--- Log opened Tue Oct 12 00:00:33 2021
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06:26 < Llamamoe> Does anyone know if there's any substances that target pathways that promote ketogenesis?
06:38 < kanzure> Llamamoe: https://en.wikipedia.org/wiki/PPAR_agonist
06:39 < kanzure> upregulates lipase activity.
06:39 < Llamamoe> kanzure: Ahhh, crap. I knew about the metabolic impact of PPAR receptors, I should have jumped straight to looking that up 
06:39 < Llamamoe> And yeah but lipid metabolism and ketogenesis, while related, are still two different things
06:40 < kanzure> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212005/
06:43 < L29Ah> Llamamoe: metformin
06:43 < Llamamoe> For context, I'm asking because my reading has all been slowly converging on virtually every mental ailment implicating brain energy metabolism, most commonly through dysregulation downstream of disturbed sleep, most of the time Sleep Disordered Breathing in particular
06:44 < Llamamoe> I've achieved immense remission of my depression, anxiety, and moderate of ADHD symptoms, through the use of a BiPAP for my condition, but I've hit a wall that I can not cross without airway surgery 
06:44 < Llamamoe> And ketone bodies are particularly interesting as they are an endogenous alternative pathway
06:44 < nsh> heh
06:44 < Llamamoe> One with papers clearly demonstrating their positive effect on brain network stability
06:45 < Llamamoe> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084077/
06:45 < Llamamoe> My tl;dr: Ketones increase brain energy availability independent of metabolic status, and increase stability of brain networks (as opposed to glucose which has the opposite effect), reversing some of the impairment found in brain aging(starting around 47yo, accelerating around 60), insulin resistance, and neurodegenerative disease implicating brain hypometabolism. Brains likely enter ketosis within 10-12h of fasting, and ketone bod
06:45 < Llamamoe> y availability increases synaptic plasticity(via NMDAr density) and general cognition, likely mediating a significant portion of benefits reported with intermittent fasting, caloric restriction, and exercise. It also reduces blood glucose spikes.
06:52 < Llamamoe> For fuck's sake, I want to post my digests on github but their markdown is screwy
06:52 < Llamamoe> Okay whatever, here you go: https://gist.github.com/Asmageddon/f9b26ebc70aa7487153467d8f2130249
06:53 < Llamamoe> This is on exogenous ketones alone 
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09:13 < lsneff> So, fasting is a decent way to induce ketogenesis?
09:58 < kanzure> .title https://nature.com/collections/cicghheddj
09:58 < saxo> Brain Initiative Cell Census Network
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13:06 < Llamamoe> lsneff: Yes. But unless you want to lose weight, doing keto is a better idea, and you can just supplement C8 oil a few times a day instead
13:06 < Llamamoe> As far as I can tell, virtually all benefits of ketosis are due to presence of ketone bodies and not anything else, and exogenous supplementation works just as well
13:07 < Llamamoe> Seems to replicate the longevity benefits of intermittent fasting and exercise on metabolism, too 
13:10 < L29Ah> so can i just drink a lil acetone/isopropyl alcohol?
13:11 < Llamamoe> Octanol metabolises into Octanoic Acid(a.k.a. C8 oil) and then into BHB, if you really want it to be alcohol 
13:11 < Llamamoe> But it induces sensory changes to the tongue 
13:11 < Llamamoe> And who knows what else 
13:12 < Llamamoe> It's not particularly toxic at least acutely, but I struggle to think of any reason to choose it over C8 oil xD
13:12 < L29Ah> i don't want long stuff, long pure stuff is hard to get unlike acetone/IPA
13:12 < Llamamoe> L29Ah: Check my digests, I've got papers on what stuff metabolizes to ketone bodies there 
13:13 < L29Ah> fats do, but PUFAs aren't shelf-stable and saturated fats seem to be unhealthy
13:14 < Llamamoe> BHB salts/esters themselves, Caprylic Acid(C8 oil), 1-Octanol, 1,3-Butanediol 
13:14 < L29Ah> fatty acids, that is
13:14 < Llamamoe> 1-Octanol is a cheap solvent
13:15 < Llamamoe> L29Ah: I think they usually sell them conjugated to TAG anyway
13:23 < Llamamoe> Tbh
13:23 < Llamamoe> I just wish I could get Lysophosphatidylcholine-EPA
13:23 < Llamamoe> And I wonder if LPC-C8 would provide brain-exclusive ketone body supply 
13:24 < Llamamoe> But I guess it'd be impractical for the doses required anyway 
13:24 < Llamamoe> God I wish I had a lab, could function, and all that 
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16:59 < jrayhawk> AFAICT saturated fats are only unhealthy in the presence of genetic lipoprotein processing disorders and MUFA deficiency
16:59 < jrayhawk> or, rather, only more unhealthy than MUFAs
17:00 < L29Ah> https://en.wikipedia.org/wiki/Saturated_fat#Association_with_diseases
17:03 < jrayhawk> Most of that is insane sophistry from the American Heart Association chasing big ag money; we ran the RCTs back in the 70s and 80s demonstrating reduced mortality.
17:04 < L29Ah> could you please edit the article then?
17:04 < jrayhawk> There's actually a really convenient heuristic for determining if a saturated fat and heart disease meta analysis is written by hacks...
17:05 < jrayhawk> Which is whether or not they include the Finnish mental hospital study.
17:05 < jrayhawk> No thanks, I'm not about to get into a Wikipedia editing fight with a multi-billion dollar industry.
17:10 < jrayhawk> https://www.semanticscholar.org/paper/A-Controlled-Clinical-Trial-of-a-Diet-High-in-Fat-Dayton-Pearce/f6160c8f7daae8617a0df075fe1471ab0413c690 you can see from figure 14 the mortality curve actually get better as membrane turnover occurs
17:13 < jrayhawk> https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4784525/bin/ramc007634.f2_default.jpg similarly with the sydney diet heart study, but it didn't last quite long enough
17:16 < jrayhawk> well, and, i guess it was not using supplementary animal fats like the LA VA Hospital study was.
17:16 < jrayhawk> so maybe it was never going to produce a positive result over baseline
17:19 < jrayhawk> you have to keep in mind that the AHA rose to prominance on a grant from Proctor and Gamble for the purposes of promoting partially hydrogenated rapeseed and soybean oil, and currently props up the multi-billion dollar statin industry.
17:22 < jrayhawk> That big house of cards comes tumbling down once we stop externalizing the job of auditing the legitimacy of medical authority to the medical authorities, and start reading the randomized controlled trials.
17:25 < L29Ah> ok, i hope i'll edit it tomorrow and have fun :P
17:26 < L29Ah> meanwhile i bought a 1546 years worth of iodide supply after deciding that eating I2 isn't great
17:26 < jrayhawk> that's just planning ahead for both immortality and an exceptionally long nuclear winter
17:27 < L29Ah> that's just 100g being a minimum amount of NaI to buy
17:35 < jrayhawk> FWIW homozygous ApoE4 is probably the most widespread lipoprotein processing disorder of concern, which is 10-20% prevalence in most regions. It mildly dysregulates brain metabolic pathways in the presence of high lipoprotein concentrations.
17:35 < jrayhawk> Familial hypercholesterolemia is much scarier, but under 1% of the population
17:39 < jrayhawk> Folks with FH have very good reason to rely on MUFAs and cholesterol over SFAs.
17:44 < jrayhawk> fenn: once we get outside of the CDC's domain of economic influence, the association between vaccination and myocarditis/periodontitis for children increases dramatically; a hospital in ontario wound up with 1-in-3000 diagnosis in male teenagers, and some countries got greater prevalence by actually going looking for it.
17:46 < jrayhawk> the bioaccumulation of spike protein in the privileged circulation of reproductive organs is also quite scary and we don't know yet what that's going to do to fertility
17:46 < jrayhawk> some of this stuff is going to take years to become observationally apparent
17:51 < jrayhawk> we would've gotten much better epistemology by preventing vaccine trials from treating their control groups at the end of trials, but policymakers are just as hungry for that budget and prestige as the pharma companies themselves are, so they just mandate the epistemic minimum that will absolve themselves of accountability
17:52 < lsneff> https://arxiv.org/pdf/1511.00083.pdf
17:52 < lsneff> “Why Neurons Have Thousands of Synapses, A Theory of Sequence Memory in Neocortex” (2015)
17:53 < lsneff> Quite an interesting neuron model + machine learning system that uses them
17:53 < lsneff> Seems like a conceptual model of a biologically plausible neuron model
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19:11 < fenn> i don't see why a new vaccine technology is scarier than a new virus
19:11 < fenn> i suspect people would be complaining regardless of whether it was a new tech or not
19:12 < fenn> supposedly myocarditis is a result of accidentally hitting a vein instead of intramuscular injection; maybe kids jump more when being injected
19:12 < fenn> let's all move to new zealand
20:19 < jrayhawk> well, as with incomplete or narrow antibiotic use, overly-narrow-antibody-targeting vaccine use produces worse outcomes due to mutation pressure
20:22 < jrayhawk> so we're both forced into having repeated vaccine exposures to maintain a 1/13-1/27 hospitalization/mortality OR immune response, and additionally dealing with new strains that are going to force new vaccines
20:24 < jrayhawk> although in the case of children there's not a lot of reason to bother since they only rarely have metabolic or immune disorders to begin with
22:01 < lsneff> huh, apparently C. Elegans neurons function quite differently from mammalian neurons—more sub-threshold activity
--- Log closed Wed Oct 13 00:00:34 2021