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InquilineKea

My random notes/stream of consciousness thread

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JmuttSlSSlepry o24 naashtor ce8:irm41nd dgcAcrM
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This argues against your protein intake hypothesis, doesn't it, ?
 
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did you read the paper?
 
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You didn't answer my question, but ok, of course I read it. Lowest all cause mortality risk at ~17% total protein intake. That's not a low-protein diet!
 
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these are just epidemiological association studies like those showing that Bmi 25-30 is associated lower mortality than bmi<25. Many confounding factors and many other studies showing the opposite. Look at big picture as I have written in my book, many factors to consider that an epidemiological study cannot dissect.
 
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Levine ME, Suarez JA, Brandhorst S, et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014;19(3):407-417. doi:10.1016/j.cmet.2014.02.006
 
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Veronese N, Li Y, Manson JE, Willett WC, Fontana L, Hu FB. Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study. BMJ. 2016;355:i5855. Published 2016 Nov 24. do…
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Your 2014 Cell Metabolism paper was included in their analysis.
The big picture is your argument is that people eat too much protein, which is bad for health. This data disputes that hypothesis.
 
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Many other data (animal, basic, epidemiological and clinical) support my hypothesis. One epidemiological paper with HR of 0.95 is not enough to disprove my hypothesis.
 
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It's not 1 paper, it's a systematic review of 21 papers for the association between protein intake with all-cause mortality risk.
 
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yes yes with many contrasting data....
 
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I was actually invited to participate in this paper, which at first I agreed to. However, there were a lot of statistical issues that I raised and the authors refused to account for them and do any sensitivity testing. I therefore excused myself as a co-author after spending considerable time reviewing and commenting.
 
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Thanks . Had the statistical issues been addressed, do you know if protein intake would’ve been significantly associated with all-cause mortality risk?
 
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from what I remember, the results were heterogeneous across studies (likely due to what had or hadn’t been adjusted for and what population was considered). What I believe the authors did was just take the results that agreed with their hypothesis and exclude other studies in the final result. However, this was 2017 or 2018, so my memory of the results is fuzzy.
 
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Without knowing the pool, the lower protein intake could be from people of lower economic status as more protein usually equals more affluence. So lack of medical care, poorer overall diets, etc could be confounding factors. More plant protein would also equate with a more affluent diet as starch is cheap and not as nutrient dense.
 
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I get your point, Claudine, but when data for 21 studies are included, all that (and other) variability in the data would potentially lead to no significant associations. That these associations are identified across many different studies adds strength to the data, imo
 
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I still would like to see their diets. A diet low in fruits/vegetables, legumes and higher in starch and processed foods alone would account for this.
 
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plant protein equated to affluence? I think you mean animal protein intake is affluence, especially in 3rd world countries, where meat is expensive.
 
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no, many people eating higher protein diets also do so with greater vegetable intake and nuts/seeds. Protein powders and fake meats are more expensive then the real thing. Only beans are high in protein thats cheap and mostly low protein diets revolved around processed grains. Most people going veg do so by eliminating meat and upping baked goods and pastas/breads, not beans and vegetables. Those that do have a higher level of education and are more affluent.
 
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I do feel people eating higher in plant protein with legumes and vegetables being higher, live longer as that is a more nutrient dense diet in general. Rather then the protein alone.
 
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i thought you were talking about money and socioeconomic status, affluence = being rich, wealthy.
 
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even though the debate ensues, I feel strongly about the plant protein intake conclusions from this study.
 

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JdltSupnolyhtn o2edns9 ctaetor 5oa:e59 PeSMdSln
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Does anyone know what chemical motifs on a drug/chemical make it prone to oxidation/not being able to be safely stored for like 10 years?
Like, I have high confidence that certain molecules (like Adderall and caffeine) are super-stable even after many years [stims are SO easy to test], but, like, people say that acid is unique in degrading quickly under heat [it also is HUGE and has a lot of functional groups that make it susceptible to degradation - but I know cases where people stored it unrefrigerated for two years in a climate similar to that of NYC and it still says just as potent]. I sometimes wonder the same for, like, 5 year old Vitamin B12 [or like for most of my 5-year old B vitamins)
Do you think that double bonds or nitrogen motifs are more susceptible to oxidation? [oh hai, metformin is full of nitrogen motifs]. I'm really curious how this applies to racetams
What of sulfur motifs? [i can certify that modafinil/armodafinil can remain potent after at least several years]
what of Vitamin D?
usually, drug expiration labels come well before the actual expiration comes
The psychoactive drugs probably are easiest to test b/c people notice if they have reduced potency. No one notices if 5-year old Vitamin D has reduced potency...
 
 
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Trace oxidation can occur at a lot of functionals. It may only affect a small amount of molecules in the entire bunch (i.e. #mol), but you can assume that all substances degrade at some rate, especially in air, moisture and sunlight.
 
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yes TRACE oxidation, that's why people often talk about 70% or 80% potency. I wonder if number of functionals makes it more susceptible to oxidation [that's why ppl say acid is so uniquely susceptible to oxidation, but im also interested in this as it pertains to B12]
 
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I have a collection of functional groups you can look over to see the kinds of bonds and structures that are known in the scholarly literature. Oxidation is the process of increasing the covalency of an atom by raising its oxidation state (more positive) and removing electrons from the atom. Reduction is the reverse process (decreasing the oxidation state of an atom or adding electrons to it). The two processes never occur independently of each other. The chemical that is being oxidized also reduces the oxidizer. https://www.facebook.com/Quantamania/media_set?set=a.2623559380995172&type=3
 
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oh yeah well you know the nitrogens on lysines and sulfur on cysteines and site-8 of guanine [8-oxo-guanine] are easily oxidized [AS IS THE -OH SITES OF DOPAMINE WHICH MAKES IT SO PRONE TO FORMING QUINONES !!] but like for molecules in air rather than …
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how well do sugar alcohols resist oxidation/last anyways? Like A LOT of foods are just horrible at resisting oxidation even though sugar itself lasts forever
 
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"When oxygen is present in cells, polyphenol oxidase (PPO) enzymes in the chloroplasts rapidly oxidize phenolic compounds naturally present in the apple tissues to o-quinones, colorless precursors to brown-colored secondary products"
obv this doesn't exist in drugs
 
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"Although dopamine is normally broken down by an oxidoreductase enzyme, it is also susceptible to oxidation by direct reaction with oxygen, yielding quinones plus various free radicals as products.[25] The rate of oxidation can be increased by the pres…
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Enzymes aren't present in small molecule drugs.
OH groups on their own aren't particularly reactive. C=C double bonds are a bit more susceptible to oxidation but it depends heavily on the presence of neighbouring groups. Are you familiar with keto-enol tautomerization?
For any reaction that occurs in sufficient proportion you can find a way to push those darn arrows.
 
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Many, if not all medications or recreational drugs are in salt form. This generally makes them very stable. anything that is a liquid or an oil is going to be less stable than something that is a solid salt.
 
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Most things are susceptible to UV light and free chlorine, it's just that LSD is stored and used in such vanishingly small quantities that its loss becomes especially noticeable (like 1 dose of LSD vs. Cocaine in tap water - LSD is in such small quantities that the free chlorine rapidly reacts with it, but cocaine is also readily hydrolyzed - there's just much more to begin with).
 
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hahaha, just the thought of it! cocaine in tap water...
 
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imagine the smell (well, except analytical grade cocaine.HCl is odorless).
 
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That's a great question. I have wondered about this myself particularly since there are instances where one would want to store a drug or supplement for far longer than expiration date. It is well known that expiration dates are very conservative and assume that the chemical is stored in far from optimal conditions. A lot of things are close to full potency far beyond the expiration date even more if stored unopened in dry dark cool places. Question is how far can shelf life be extended and how much do they degrade. This will be highly variable depending on a lot of factors. made a great point about salts. Some supplements like alpha-lipoic-acid are not so stable in their pure form, but when complexed into a salt (such as sodium-R-alpha-lipoic-acid) the stability becomes far greater, as long as it is kept away from humidity. I wish there was a database for actual degradation under normal storage conditions for various drugs/supplements. That would be useful.
 
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Are sell-by dates on vitamin bottles not the product of research in this area done already?
 
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surprisingly I don't believe they necessarily are 😬 it's a very unregulated market
 
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Coming back to some of the other points, molecules of high molecular weight which are sensitive to be completely destabilized by single electron abstraction (e.g. by naturally generated radicals) are going to be especially sensitive to passive environmental conditions.
Many of the drugs with the greatest atmospheric degradation are both extremely hygroscopic and labile to hydrolysis - that is why most people work hard to remove moisture (silica gel packets etc.).
I believe LSD is especially susceptible under light as it has an electron easily lost to UV excitement (allowing reaction and deactivation of the radical by whatever it contacts e.g. atmospheric water) as well as attacked by sporadic radicals.
Of course correct formulation is able to allow almost anything to be indefinitely stored by a consumer, whether that's with coatings, antioxidants, etc.
 
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Lysergic acid salt, deposited on a piece of blotter paper and stored in a folded sheet of paper, which is then tucked in pages of a book, is going to be good for a very, very, very long time.
 
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LOL ONE OF MY FRIENDS FOUND YEARS OLD ACID BETWEEN PAGES OF A BOOK
 
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and took it and it was potent
 
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Decades
 
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man if acid lasts for decades, then most other drugs should
 
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acid is uniquely brittle b/c complexity
 
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right, LSD tartrate, away from UV, bleach (incl in paper), etc. is stable indefinitely, and that's despite its sensitivities; if it's not got a surprisingly narrow Gibbs free energy (and is not passivating) it's not gonna spontaneously react.
 
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"if it's not got a surprisingly narrow Gibbs free energy (and is not passivating) " how do you know? don't buckyballs also have the same time? what of chlorophyll and other molecules full of double bonds that absorb free radicals?
 
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they are regenerated by their local system
 
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isnt it the same for ascorbic acid?
 
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ascorbic acid can generate a non-reactive product from reactive oxygen species, it's a sacrificial attenuator.
 
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"sacrificial attenuator" LOL WHAT DO YOU MEAN BY THAT SO CREATIVE
 
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If you have something which regularly reacts with reactive oxygen species to produce a non-reactive product it's an antioxidant, but many antioxidants do not spontaneously reform their original state without external action (enzymes, etc.)
 
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Repeat after me "Store in a cool, dark place". 😉
 
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It's related to energetic stability. The reason LSD and it's analogues go bad is mainly due to heat, light and then air exposure and humidity. Remove the first two and it lasts significantly longer as far as potency is concerned. it is due to the eletromagnetic stability, polarity and also it's proneness to be affected by incoming heat and light waves.
 
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wow, so acid has low electromagnetic stability/polarity?
 
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All molecules have different profiles yes, depending on the geometry and charge of the atoms
 
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Geometry of the bonds and also the charges of the atoms (which are linked by bonds)
 
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If I'm not wrong, it's how our receptors accept neurotransmitters and substrates
 
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what would you say is the energetic stability of C60 then, or or highly-polyunsaturated fatty acids? [and carotenoids and melanin?]
 
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astaxanthin is protective against ionizing radiation
 
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delays sunburns IME
 
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but I use it mainly as a substitute for Acutane, but plus I can go in the sun
 
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do you actually think that a lot of antioxidants are so effective precisely because when they DO absorb energy that energy is heavily delocalized across the molecule/antioxidant in a way that doesn't significantly change the antioxidant's free energy (sometimes allowing it to more easily switch back and forth states?) one can say this for ascorbic acid and some of the carotenoids which are choked with double bonds. and somehow this makes it energetically favorable for them to TAKE IN free radicals, rather than have the free radicals attack a lysine or cysteine or guanine site?
i mean, but i wonder if this ALSO means carotenoids don't store as well long-term? i have several-year old lutein that has been through 3 boston summers already...
PUFAs easily go rancid and the main structural difference between them and carotenoids is just the SPACING of the double bonds (with PUFAs they're separated by 3 and unable to undergo resonance)
I mean, buckyballs also have huge amounts of double bonds and are also antioxidants, but i wouldn't trust the ability of them to easily leave the cell
 
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Huh, interesting idea, I've never thought of it from that angle. You may be on to something. Not sure about C60 however I shall read on it.
 
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If you dont have AC I'd just get some Astaxanthin instead of Lutein, it dosen't become pro-oxidant, when ingested or when exposed to UV. I mean, it must be ubiquitious in marine life for a reason....
 
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, ascorbic acid is not your regular antioxidant. It is a 3 billion year old redox molecule that can be regenerated after it donates electrons. The body uses the redox feature in a lot of important biological processes, including the synthesis of nitric oxide and catecholamines like dopamine and norepinephrine. It is also used to maintain iron in the ferrous state.for absorption and keeping heme in stable reduced state.
 
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, good questions. Antioxidants generally have reactive pi systems that delocalize odd electrons, missing or extra. It works both ways. Also charge delocalization, as in the case with ascorbyl anion and radical. Carotenoids are much more stable than…
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, the Buckyball systems are unique among antioxidants because of their bent pi systems. Most aromatic antioxidants have flat pi systems. One exception is hypericin (and pseudohypericin), which have a twisted aromatic system due to steric crowding of phenolic oxygen atoms. This twisting allows hypericin to pi-associate with a triplet oxygen atom and pair up its electrons. With a UV photon, the singlet oxygen is kicked off, to do damage or therapeutics, depending on the situation. For C-60, the pi systems are fully redundant, being fully spherically symmetric. But for C-70 and C-80, the pi systems are split into multiple energy bands. These might be superior (or not) for that reason. It is also possible that an ion or transition element inside the Buckyball would interact with the inner pi bonds and affect the outer bond interactions, although I doubt that we have the technique to build such structures. Yet.
 
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I'm sure some supramolecular lab somewhere is looking into that. Do you know of naturally-occurring coordination complexes like chlorophyll and hemoglobin that have bent or twisted pi systems?
 
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, I only ran across hypericin and pseudohypericin due to my volunteer work with the San Francisco and Seattle HIV underground. It is not something that I have looked into on a general phytochemical basis. Hypericins are naturally produced by hypericum perforatum (St. Johns wort), AKA "goat weed" in Eastern Washington and Oregon. It's ability to catalyze singlet oxygen from oxygen and sunlight can kill cattle and sheep which graze on it. RBC hemolysis, so likely an anti-GSH mechanism. But goats seem to be able to eat it. Ranchers use goats to get rid of it.
 
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Some molecules have very unique reactions to any sort of incoming rays. Some even are protective against ionizing radiation, which is quite spectacular.
 
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huh what molecules?
do you have a biochem backgroun d btw?
 
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In case of the skin or eyes, singlet oxygen generated from UV rays plays a major role in harmful effects. http://pmid.us/17363921
Carotenes are particularly effective scavengers of singlet oxygen and therefore at protecting against UV radiation. It's not surprising that plants and animals evolved to use carotenes to protect against UV light.
 
Direct detection of singlet oxygen generated by UVA irradiation in human cells and skin - PubMed
PUBMED.NCBI.NLM.NIH.GOV
Direct detection of singlet oxygen generated by UVA irradiation in human cells and skin - PubMed
Direct detection of singlet oxygen generated by UVA irradiation in human cells and skin - PubMed
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See previous conversation we had on antioxidants (Vit C, Lutein, Astaxanthin, C60). I don't but I had a lot of knowledge rub off on me, I have worked in a lab as a student job however and read articles (pubmed etc) to further my own knowledge.
 
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The first post, discussion with Fontana, Lustgarten, Levine and others was interesting. It shows how misleading literature articles can be and how hard it is to interpret them properly.

There is no solution to this, other than trying to build up a conceptual framework, degree of belief and try to assess the reliability of sources.

 

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It is well known that MUFA rich diet exerts an anti-inflammatory, antioxidant effect (3032). Despite an equal proportion of MUFA, PUFA, and SFA in the HF meal in this study, we only observed a modest/minimal effect (on postprandial gene expression as well as urinary F2-isoprostanes) exerted by HF meal. The total caloric content as well as SFA proportion was much higher in previous studies as compared to that in our study (11, 32, 33). The deficiency/lack of relative and absolute amount of SFA in the HF meal could have contributed to the more modest changes observed in our study, both in postprandial MNC gene expression and systemic F2-Isop responses (34).

 

 

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