Posts made by cs3000

@Ismail posts on the subreddit as lurkingheretoo

@Mauritio i found a study matching nearer Peats dose, shows it very effective for giving a protective effect in stress at ~ 1ml human amount 0.05ml/kg rats. so i guess that amount would be helpful like u mentioned with an oncoming cold (helpful to prevent inflammation & oxidative stress extremes)

https://onlinelibrary.wiley.com/doi/10.1155/2021/4475968

• We found that low-dose alcohol (0.05 g/kg, i.p.) ameliorated {acute stress} AS-induced renal dysfunction and histological damage. Low-dose alcohol also attenuated AS-induced oxidative stress and inflammation, presenting as reduced malondialdehyde and hydrogen peroxide formation, increased superoxide dismutase and glutathione activity, and decreased myeloperoxidase, interleukin-6, interleukin-1β, and monocyte chemoattractant protein-1 levels
  Moreover, low-dose alcohol alleviated AS-induced apoptosis by downregulating Bax and cleaved caspase 3 protein expression

Stopped the stress induced cell death, h2o2 oxidative stress increase, neutrophil infiltration, in very "small" amounts,
pretty good ay

maybe small amounts diluted could be good for colitis

Crossing open field test (exploration )

0.7ml/kg in mice (~5ml <10ml human but maybe best to go a bit lower closer to 1st study adjusting for mice ability to react less to it)
gave peak protective effect in stroke
1.4ml/kg started losing the effect . In mice , who could be more resilient to overdoing ethanol
https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00006/full

@Mauritio might give it a go on the low end

at least a big part of the effect of those mice studies looks like from increasing their movement a lot,

so human rodent differences aside if u arent suddenly moving a lot more from it i dont think the effects gonna be similar. maybe the protective effect on the low end could give some of the gains there outside of the movement

With the theoretical maximal oxidation rate of alcohol being 0.1 g·kg−1·h−1 of lean body mass (Schutz 2000), it is unclear to what extent alcohol ingestion prior to exercise can alter exercising substrate use. https://academic.oup.com/alcalc/article/59/2/agad079/7425522

@Mauritio might tip over there and the toxicity / inflammatory reactions could shut down the metabolic effect, its even different between species in rodents (or different in the brain alcohol is metabolised different there i think),
e.g 1 of the studies showed 0.25ml/kg fed to rats boosted metabolism in their brains, but going to 1ml/kg didnt boost metabolism & lowered brain metabolism below controls. maybe someone's tested low amounts like 5ml on humans would be cool if there was similar metabolic effect co2 production etc

~18ml ethanol didnt show antioxidant capacity in humans (beer didnt give much effect either) https://www.sciencedirect.com/science/article/abs/pii/S0955286399000777
(ethanol stimulated polyphenol absorption. but beer polyphenols have estrogenic effect from the hops)

@CrumblingCookie not aware of the narratives but human toxicity dose was 270mg & 400mg so didnt need that higher dose
some polyphenols chelate copper more than iron , copper can be damaging in high amounts but also vital for mitochondria so if someone over focuses on eliminating it their mitochondria suffers
(TSH starts to rise in some studies that use 100s of milligrams of some polyphenols too , maybe binding too much iron copper zinc so they cant be used for regular functions enough. i guess copper is especially vulnerable because lower amounts / intake. e.g too much quercetin is detrimental to complex IV activity in mitochondria alongside ceruloplasmin :

Quercetin is an iron & copper chelator
it lowers ceruloplasmin 50% , injected in mice at 50mg/kg mice dose
, In the present study a decreased activity of Complex IV in mice treated with quercetin is clear. This is well correlated with decreased levels of ceruloplasmin. {copper protein}
Our previous research [30] exposed that mild copper deprivation in mice is correlated with a decreased protein expression and activity of Complex IV at the level of OXPHOS supercomplexes along with a decrease in the ceruloplasmin levels

@Mauritio looked into that a few days ago because great outcomes in rodents but would be very high amounts for a human going by effects,

(rodents are probably a lot more resilient to ethanol than humans, i think they're better adapted probably because of eating high amounts of fermented fruit on the ground vs primates who pick a lot with smaller ethanol amounts)

ray said 1 tea spoon for protective effects (diluted, ~3ml - 4ml) (cognitive protection on lower end brain atrophy on higher

full reply at the bottom https://www.reddit.com/r/raypeat/comments/1hrc3pf/comment/m5u70mo/

@BeefEnjoyer
(idk how relevant but 10,000iu is excessive, 1000iu should be enough thats 10x)

can be a fix there potentially , here's a relevant post

https://www.dinet.org/forums/topic/25217-excessive-salivation-anyone/
had hypersalivation for 4 years. I finally figured out that my high daily dose of vitamin d (5000 iu) was causing it. No doctor ever figured that out because there is no literature to support that. my salivation returned to normal about 3 days after I reduced the dose to 2000 iu. however, during those 4 years, I successfully managed my hypersalivation with the following products

{2 people in this thread mentioned vitamin D} {magnesium has some interplay with vit D that could make vitamin D problems worse, posted info on that in a thread here, which fits with this persons experience too)
The only thing I've been able to relate it to in the past is sometimes I might have taken too much magnesium. At those times I would back off of magnesium and the problem would clear up. However, this time I am not taking magnesium but still have the problem. I have been taking my prescription vitamin D

might be worth a test stopping all vit d intake for a time and not getting a lot of UV for it to be sure
(i would try stopping for 2 weeks considering 10,000iu vs 5000iu, letting it reset decently. my twitching from vit D took a few weeks of stopping to lower.
also being in calorie surplus during this is important so you're not releasing a lot of vit D from lipolysis , + i personally would go a step further to make the test extra solid & pause exercising for the same reason until satisfied with whether its helped things or not https://onlinelibrary.wiley.com/doi/full/10.1111/nbu.12369)

, then if it helps maybe re-adding vit D lower e.g 500iu initially

but if no effect from doing a proper test for a few weeks
more info on saliva secretion & hypersalivation
https://akjournals.com/view/journals/2060/107/2/article-p195.xml

there's human trials

cognitive improvement
https://www.ls-corporation.co.jp/wp-content/uploads/2022/10/ergothioneine_congitive.pdf

and over 1 year, with people aged > 60
https://www.medrxiv.org/content/10.1101/2024.07.08.24310085v1.full.pdf

at 6 months, and still gaining at 12 months

. Following ET intake, an increase in Z-scores was observed in RAVLT assessments (immediate and delayed recalls), which evaluates learning ability and memory (Figure 4a&b). In contrast, no significant increase was observed in Z-scores across all NCA components, in the subjects given the placebo.
Block design scores, which assess visual-motor coordination and problem-solving skills, declined over time in both ET and placebo groups (Figure 4g). Although not measured at baseline, Z-scores of SDMT (written format) in the ET group showed a trend to increase from visit 7 to visit 14 (Figure 4i)

(at 4 weeks visit 1 ergo group also had a better lymphocyte-neutrophil ratio)

Another good one ,
gives weight to ergo as the main compound in mushrooms that gives the main cognition improving effects vs b-glucans

giving mice deficient diet for 5 weeks
then refeeding 3x a week for 2 weeks (2mg/kg or 20mg/kg)

discrimination index (DI), an indicator of learning and memory ability
restored by either amount (and higher than controls) , took 2 weeks

(smaller amounts likely work the same too just with a longer buildup , amounts build to 4 weeks its half life)

https://pmc.ncbi.nlm.nih.gov/articles/PMC10847428/#Sec2

something interesting is their hippocampal levels didnt restore to controls at 2mg/kg vs 20mg/kg by 2 weeks, but still got the effect. i wonder how much mice usually get & where from. ive seen adding 0.5mg/kg bw to normal mice diet gave behavioral improvements in another study posted here

neurogenesis

@DavidPS

**But there's a potential problem getting it through mushrooms, https://pmc.ncbi.nlm.nih.gov/articles/PMC8329194/#Sec2 mushrooms antagonistic to androgen receptor
they stop DHT increasing androgen receptor in multiple tissues & can lower vs controls in some tissues

ive noticed a flat mood effect from mushrooms before
heq low amounts 1g-1.5g of white button mushroom water extract (so probably not the ergo, likely b-glucans which are found in way higher amounts)

(the beta glucan content has effects ~250mg here , closely matching white button https://pmc.ncbi.nlm.nih.gov/articles/PMC11467013/#ctm270048-sec-0070)

shiitake has 1g/10g cooked b-glucan

here a b-glucan lowered estrogen in the prostate where elevated (normalized in prostate and also normalized low testosterone / AR doi: 10.1039/c4fo00472h ) there's an anti androgen receptor effect pretty potent across tissues by earlier study though using mushroom water extract

mainly because of the high beta glucan content

Here white button mushroom lowered AR in vitro, but in the mice tumors in vivo AR expression didn't lower, even tho tumors shrank (at least short term) (tho its not healthy tissue like the 1st study showed)
https://pmc.ncbi.nlm.nih.gov/articles/PMC8542389/#S17

*maybe a supplement is best if doesnt also include the mushroom powder.
or taking 2g spirullina , if dont respond well to androgen reducing stuff

--
also for ppl eating, wondered if microwaving destroys the ergothionine, nope all ergothioneine stays intact
https://www.jstage.jst.go.jp/article/fstr/25/1/25_115/_pdf/-char/en
Best not to boil them 2/3 of the ergothioneine gets drained
Roasting is good and frying should be ok too can pour the fat into the food

@Korven some benefits at low dose but its toxic in the 100s of miligrams over time, supplement doses
(& ironically low copper makes mammals more vulnerable to it)
(similar thing to high dose quercetin probably, where its chelating too much copper over time for diet to match. plus the ROS damage from excess)

https://pubmed.ncbi.nlm.nih.gov/25975988/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943924/

But not great to go high copper to prevent that as can cause other problems from the excessive copper , "low" mg doses of catechins should have some benefits

@Mauritio @Serotoninskeptic nice insight ty

Japanese and Okinawans were similar for averages (Okinawans had less disease too though) doi: 10.1196/annals.1396.037
(average, maximum) for Okinawans (83.8 years, 104.9 years) compared to other Japanese (82.3 years, 101.1 years),

nearly 1/2 the pufa intake , relatively high for fat % but they also ate 16mg vit E which helps counter pufa vs 6mg with the other japanese (less vit E with more pufa). 9% protein & 13%.

check this https://journals.physiology.org/doi/full/10.1152/ajpregu.00834.2004

(^ I wonder if there's some exponential element to vit E need for higher pufa intake? other studies havent replicated that with lower, and their diets typically high in pufa. but rats are usually fed high vit E as a baseline already.
extreme dose not needed to counter a lot of the pufa, especially with lower intakes seen here. both also ate >200mg vit C too i think which helps vit E function, if the other japanese ate 16mg too would it have closed the disease gap a lot? which was still much better than usa)

Around 10% protein is what they use in a lot of studies, so that seems to be a good goal.

this was a good one, with 10% fat and ~80% carb diet (13% as sugar), (7% protein vs 13% vs 7% + bcaa,
they added 1.8g l-cystine to 70g casein (casein doesnt have much as only protein source, some cystine needed e.g for the sulfur reactions)

(mrna expression, in liver)

https://pmc.ncbi.nlm.nih.gov/articles/PMC6073443/#sec5-nutrients-10-00918
so 10% protein in the middle would still give a fgf21 ucp1 boost

their lean mass & bone gain suffered on 7% but some gain
yeah bumping up to 10% might be best of both

nice ergothioneine overview
https://nutritionfacts.org/video/dietary-sources-of-the-longevity-vitamin-ergothioneine/

**even eating 20g of white button mushroom daily gives a good amount with good effect (1mg), thats already bumped up a bit but for variation in amounts could go 30g, likely sorts ergothionine effects that japanese are getting with their great healthspans

-> 2 servings of mushrooms a week = 1/2 the odds of cognitive impairment

https://www.researchgate.net/publication/346870796_Is_ergothioneine_a_'longevity_vitamin'_limited_in_the_American_diet
(i think their estimates are off going by absolutes, when u look at the doses that have effects and the amounts in foods that arent mushrooms, but if their relative amounts are close its interesting) @luke

The reason it says 1mg for USA is because its including the mushroom consumers, which are only 10% of the people surveyed, so skews the number upward. if they hit the 1mg i think they'd be closer to italy ireland france

Doi: //doi.org/10.1080/10807039.2015.1104241

also this

recent longitudinal unbiased metabolomic study conducted in Sweden involving over 3200 adult men and women consuming a health-conscious food pattern at baseline sought to identify blood metabolites that could predict a lower risk of cardiovascular disease(CVD) and overall mortality(17). Out of 112 metabolites measured at baseline, they found that plasma ERGO levels were the most strongly associated with decreased risk of CVD and reduced mortality after 21⋅4 years of follow-up

@Luke I think 3 of the main factors are
1, high ergothionine intake (mauritio has a post on that),
2. a more relaxed way of being, (generally, outside of anime studios) (maybe helped created by high % of elderly population)
3. lower rates of vaccination since the 70s after children died from them and a bunch of lawsuits hit creating a more measured approach (especially with mercury being used for a while & aluminium creating extra toxic burden) (only two new vaccines were licensed in Japan between 1990 and 2007 compared to 17 in the US)

https://www.youtube.com/watch?v=RfHTcloRdIU 97 year old running a restaurant (humans in true form)

@b1 when someone drinks it for the sake of drinking it tips the balance away from salt & adrenaline goes up (i stayed up all night just by drinking water at night with hypothyroidism), also you consume more DNA toxic things from the detergents added, more microplastics,

benefit i know of is fixing dehydration and the coldness (might) stimulate thermogenesis for 30 mins to warm back up - but results on that arent reliable, e.g this found it didnt have an impact on metabolism or thermogenesis https://www.nature.com/articles/nutd201541 and that vasoconstriction preventing body heat loss after drinking water can make up for the temperature change (which fits with it causing higher adrenaline) . idk where the "x glasses a day" comes from. In that article peat said the old test for epilepsy was to give people a big glass of water and it would induce seizures. only need a little for hydration unless sweating buckets or overloading salt

@haidut @Amazoniac @Mauritio Here's something unexpected in breast tumors,

EDIT: its in HER2-enriched breast cancer , so showing nuance between cancers here

using acetazolamide (most potent carbonic anhydrase inhibitor) surprisingly they said it caused tumors to grow. even though tumor pH lowered, and lactate lowered

https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-023-01644-1#Sec16

so the beneficial Apoptosis effect you'd usually see happen in hypoxic cancered cells from the lower pH is hindered / prevented by another effect?
It didnt raise proliferation markers, didnt raise vessel growth,

The density of macrophages is high, T cells moderate, and B cells low; yet overall the abundance of these cell types is reduced by around half in breast cancer tissue from mice treated with acetazolamide compared to vehicle

so by the looks of it the lowered immune cell infiltration prevented the pro apoptosis effect

the extracellular carbonic anhydrases positively predict patient survival in HER2/ErbB2-enriched breast cancer

These observations suggest that carbonic anhydrases—likely via their ability to elevate tumor pHo (Figs. 6 and 8A)—provide an immune-stimulatory input that improves survival of patients with HER2-enriched breast cancer characterized by a weak immune response.

In contrast to HER2-enriched breast cancer, the association between extracellular carbonic anhydrase expression and patient survival in Basal-like breast cancer is seemingly unaffected by tumor inflammation

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1268421/full Acidification of intracellular pH in MM tumor cells overcomes resistance to hypoxia-mediated apoptosis in vitro and in vivo

Hypoxia-mediated apoptosis of MM cells is correlated with acidic intracellular pHi (less than < 6.6) that is dependent on HIF activity. a carbonic anhydrase inhibitor (acetazolamide), and an NHE-1 inhibitor (amiloride) acidified the pHi and lead to cell death.
In contrast, treatment of cells with an alkalization agent, Na-lactate, rescued these cells by increasing the pHi (pH > 6.6). Finally, treatment of mice with acetazolamide decreased cell growth in the tumor nodules.

{{interestingly just 40 MICROgrams/kg i.p was used to slow tumor growth there)

So this approach should be effective in cancers not characterised by weak immune response , but for those that are, its detrimental to lower pH , (at least without added ph independent immune stimulus overcoming its inhibition , if possible)
(or maybe need to really drive the pH down lower to hit <6.6 ,
so no half measures there? but i think the 1st study already would have hit most of the CA IX inhibition/co2 raise with 40mg/kg i.p right?

here 40mg/kg orally inhibited lung tumor growth a little , and drastically lowered metastasis. so whether its a helpful or harmful effect does seem dependant on immune cell characteristics (otherwise if it worked at this dose here, it shouldnt have raised growth in the other) http://www.chinaphar.com/article/view/7735/8235

@dapose @DavidPS last week in the uk ive never seen fog that thick before, and lasted through the daytime into night which ive never seen here, i said "this feels like i'm in silent hill rn". there's high rate of illness here atm. usual for dec - feb with widespread vit d sunlight deficiency christmas & lower body temps, but would also be a time of high opportunity .

@brad would be interesting if this event had thickest fog mainly in areas within 10 - 100 miles of coastlines

goog /books?id=CLCTL4woX_4C&pg=PA80#v=onepage

@Mauritio good to hear its clear ,

hmm swerved a bullet with that then, so with the macrocylcic type might be negligible amounts

https://pmc.ncbi.nlm.nih.gov/articles/PMC5647271/

it was noted that the levels of gadolinium were several-fold lower for tissue from patients injected with macrocyclic agents compared to those injected with linear agents (20 times lower for ProHance than for Omniscan) and the actual amount of gadolinium deposited was very small, of the order of a few ng g−1 of tissue.

hard to say if thats a relevant amount right, low ng/g seems very small ive seen other toxic metals found in double - triple digit nanograms per g of non cancered tissue

but for added peace of mind with whats left a boost a round of lipoic acid might be worth a try for a couple weeks? and avoiding zinc supplements during this time as seems to help retention (but needs replenishing after ofc). and 1g vit C a day might help (helps lead excrete a lot at least)

Sulfur groups bind it like the other heavy metals https://www.researchgate.net/publication/341867829_Investigating_the_role_of_sulfate_groups_for_the_binding_process_of_gadolinium_ions_in_glycosaminoglycans
(so lipoic acid which has 2 sulfur groups, msm, thiamine might be useful , as such low amounts from the macrocylcic type probably best not to take high amounts for long as run the risk of needed metal depletion, maybe a couple weeks would be significant)

@Mauritio its mostly inhibiting just the variant there (not normal androgen receptors) splice variants lack parts that de-activate them so continually active https://www.nature.com/articles/nrurol.2015.13

ironically depleting androgens in prostate cancer can induce more of them (and more significant amounts in the extracted cells part but idk how much they contribute)
https://aacrjournals.org/clincancerres/article/20/6/1590/211454/Rapid-Induction-of-Androgen-Receptor-Splice

AR-FL (normal receptors) arent getting inhibited much but AR- variants gone

|

1 found mild estrogenic activity in vitro in cancered cell lines which doesnt match with the in vivo anti tumor activity,
but mainly on ERRy and ERRa estrogen related receptor, 30% max transcriptional activity of estradiol on estrogen receptors, (maybe displacing estrogens for milder effect lower transcription? but potent on ERRs in these cells)
,

https://www.sciencedirect.com/science/article/abs/pii/S0300483X21001281

They found some hormone reducing effects in fish but idk how relevant to mammals

In adrenocortical cancer cells it reduced hormones production at nM concentration,
https://academic.oup.com/jcem/article/103/10/3706/5056322

• It has a mutagenic effect at higher end dose

humans show lymphocyte abnormalities from treatment at higher end dose. apparently its lethal in 100% of some strains of mice injected at low dose 7.5mg/kg. needs to be transformed in the gastrointestinal tract first & go through the liver https://pubmed.ncbi.nlm.nih.gov/3278217/

orally 60mg/kg ~300mg-400mg human dose starts to give a rise in abnormal sperm

its a mild effect there but thats only with 5 consecutive days

in humans the mutagenic effects on lymphocytes with 1g-2g for a day then 6 days of 500mg increased. (i'd guess red blood cells might be more vulnerable) doi: 10.1016/0165-7992(86)90015-1)

so to be on the safer side i wouldn't take >100mg of this regularly, 25mg has effects. and maybe good to have a few days off a week just incase.

@Mauritio said in Niclosamide reduces serotonin and glutamate:

Didn't you write something about cancer and pH? Niclosamide seems to affect that :
https://pubmed.ncbi.nlm.nih.gov/22474287/

cool thanks , yeah lowering pH to a certain level helps make the apoptosis process more effective