Sarcosine Is Uniquely Modulated By Aging And Dietary Restriction In Rodents And Humans

Discussion in 'Scientific Studies' started by Terma, Jan 22, 2019.

  1. Terma

    Terma Member

    Joined:
    May 8, 2017
    Messages:
    1,062
    Gender:
    Male
    Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans
    Furthermore, the major inducer of GNMT is Retinoic Acid, in other words RA produces all the sarcosine that apparently modulates the autophagy. This all makes perfect sense.


    They even throw in this freebie:
     
  2. olive

    olive Member

    Joined:
    May 17, 2018
    Messages:
    555
    Gender:
    Male
    Cool study. To put this into practice would one supplement sarcosine directly or just continue taking glycine and eating sufficient levels of vitamin a?
     
  3. Whichway?

    Whichway? Member

    Joined:
    Oct 2, 2018
    Messages:
    285
    Gender:
    Male
    What is GNMT? I can’t see it defined anywhere in that text.

    You should post this over in the Grant Generaux Vitamin A is toxic thread. They believe there is a lot to be gained by lowering vitamin A as much as possible, however I’ve seen studies where it is required for normal proliferation and maintenance of stem cells. And now this finding.
     
  4. OP
    Terma

    Terma Member

    Joined:
    May 8, 2017
    Messages:
    1,062
    Gender:
    Male
    I do both, basically. Sarcosine crosses the blood-brain barrier (I don't know to what degree it could be a natural neurotransmitter, but is NMDA agonist in 1-3g+ doses), however I don't know about its transport mechanism into cells.

    I see no reason to think RA + glycine would be particularly better because GNMT is mainly liver enzyme, so that forces the liver to do all the work and then export it to blood, even though it may be relatively "safer".

    GNMT is mentioned in the full paper link, you'll have to look around.
     
  5. bdawg

    bdawg Member

    Joined:
    Aug 21, 2016
    Messages:
    291
    Gender:
    Male
    Location:
    Sydney, Australia
    Can sarcosine be described as a glycine reuptake inhibitor due to inhibiting the transporter?
     
  6. OP
    Terma

    Terma Member

    Joined:
    May 8, 2017
    Messages:
    1,062
    Gender:
    Male
    That was the assumption behind its benefits on schizophrenia, but this opens a giant new field for it.

    Hell, for a supplement it even tastes good and foods already contain some.

    (I wonder if the body even prefers it to glycine to some extent)
     
  7. bdawg

    bdawg Member

    Joined:
    Aug 21, 2016
    Messages:
    291
    Gender:
    Male
    Location:
    Sydney, Australia
    Ive ordered some as I have schizophrenia in the family.

    Lets see the results, apparently its much more effective than glycine at hitting the glycine receptors
     
  8. OP
    Terma

    Terma Member

    Joined:
    May 8, 2017
    Messages:
    1,062
    Gender:
    Male
    Well, all I can tell you is that as someone who can't stand NMDA antagonists for long, sarcosine is like a breath of fresh air.

    That said although it works for schizophrenia, it's probably a downstream treatment of sorts, so don't get your hopes too far up:
    Sci-Hub | | 10.1016/j.psychres.2018.08.002

    The supplement company I bought from recommended using it for 6 months before judging difference (yeah... I know, but given what is found in OP there's something to it), though I didn't have to wait at all, I use it a few times a week and it does its job.

    ------------

    For the sake of full disclosure, it IS a marker for prostate cancer, but personally doesn't worry me this far:
    https://febs.onlinelibrary.wiley.com/doi/abs/10.1002/1878-0261.12439
    (keep in mind cancer cells seem to aggressively increase methylation if you try to lower it any way)
     
  9. Goobz

    Goobz Member

    Joined:
    Mar 2, 2019
    Messages:
    302
    Gender:
    Male
    Location:
    Australia
    Hi all, first time poster, interested in this topic. Will go into much more detail in a later post, but just for now...

    I wonder what the effect of sarcosine supplementation is, in comparison to high dose glycine? Both have been used for schizophrenia.

    I would assume it would mean you would preserve both your glycine (i've seen this mentioned in one sarcosine study on PD dementia, that it "replenished glycine pools") and sAME? Since those two are converted into Sarcosine via the GNMT enzyme.

    But sarcosine can also be formed from the tri and di methylated versions, TMG/betaine and DMG. I wonder how this compares to simply taking the other methylated glycines - TMG and/or DMG, as supplements?

    Interesting that disorders like Parkinsons involving protein accumulation (would seem a sign of a lack of autophagy) first present with REM sleep disorder years earlier - which researchers believe is a sign of low glycine, since glycine as a neurotransmitter is what usually paralyses the muscles during REM sleep. Also interesting that Vitamin A levels are typically low in Parkinsons patients. And that Vitamin A appears to help dissolve the Lewy Bodies that accumulate in that disease.
     
  10. Goobz

    Goobz Member

    Joined:
    Mar 2, 2019
    Messages:
    302
    Gender:
    Male
    Location:
    Australia
    (Oh and as mentioned above, Vitamin A induces the GNMT enzyme so should upregulate conversion to sarcosine)
     
  11. OP
    Terma

    Terma Member

    Joined:
    May 8, 2017
    Messages:
    1,062
    Gender:
    Male
    Well, sarcosine works at 1-4g doses in schizophrenics, whereas you may need up to 60g glycine for similar effect. (I tend to think the former is safer due to dosages alone, but who knows)

    I've taken choline, TMG and DMG, sarcosine and glycine as supplements (gotta catch 'em all). To me they feel very different but some people get an "excitatory" reaction from TMG as well as depression, which might considered similar to sarcosine's effects, but I'm not sure it has anything to do with sarcosine.

    Greetings I guess, also goodbye in case this is the last time we talk.
     
  12. Goobz

    Goobz Member

    Joined:
    Mar 2, 2019
    Messages:
    302
    Gender:
    Male
    Location:
    Australia
    Thanks for the greetings. Ive tried all those supplements as well! Haha.

    I feel "safest" with choline, TMG, and glycine, since they're part of the human diet. I read somewhere that TMG can safely accumulate in cells without impairing function. But yes as you say, 60g of glycine is anything but natural.

    But I have had DMG, which seems more like a drug, recommended to me for a chronic infection similar to Lyme (chlamydia pneumoniae) and they believe that DMG is helpful for it. Can't tell if the effects are that strong, but may possibly help me feel better.

    Sarcosine seems to make me more relaxed, but slow.

    I've also read that sarcosine and or high doses of glycine caused disordered breathing like sleep apnea in rats. Sarcosine is a glycine re uptake inhibitor in the brain, and causes more glycine to be available to use as (an inhibitory) neurotransmitter, and can inhibit breathing. I don't think I've noticed anything like this myself, but I have mild sleep apnea and need to be wary.
     
  13. OP
    Terma

    Terma Member

    Joined:
    May 8, 2017
    Messages:
    1,062
    Gender:
    Male
    That's an interesting remark about sleep apnea. Although I've had no issues with sarcosine, several people on the internet including myself have this problem with taking 3g+ glycine before bed, that causes a deep sleep for 3 hours followed by waking and inability to fall asleep again (does not seem to be blood sugar, at least for me). So I wonder if that is not related. (There are other aspects as well: glycine and sarcosine might indirectly interact with histamine and other things, but don't ask for now) However, I think the deep sleep paralysis required the combinations of GABAA+B+glycine, so it's not much a worry on its own.

    DMG I saw various positive descriptions on paper, but it did nothing noticeable (it was the Now! supplement - no idea the quality).
     
  14. bdawg

    bdawg Member

    Joined:
    Aug 21, 2016
    Messages:
    291
    Gender:
    Male
    Location:
    Sydney, Australia
    Sarcosine, beyond making me nearly fall asleep and experience some form of anhedonia after taking 3gs, has done nothing noticable for me

    I take it daily now at <1g doses as its meant to aid ADHD symptoms according to the NMDAR theory of ADHD

    For sleep, try glycine + theanine + gaba - i sleep like a rockstar despite a deviated septum. The theanine+gaba combo is supported here:

    GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. - PubMed - NCBI
     
  15. haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    17,192
    Gender:
    Male
    Location:
    USA / Europe
  16. David PS

    David PS Member

    Joined:
    Jan 5, 2016
    Messages:
    432
    Gender:
    Male
  17. OP
    Terma

    Terma Member

    Joined:
    May 8, 2017
    Messages:
    1,062
    Gender:
    Male
    That's good, thanks.

    The post above me shows empty.

    So I took my "need" for sarcosine as a diagnostic marker for NMDA under-activation and with a whole constellation of symptoms settled on taking DHEA before bed instead of more sarcosine. DHEA never did a thing good for me but it was because I took it during the day. I believe it partially fills in for growth hormone decline if you take it at night, since for one both GH and DHEA improve joint recovery in an anabolic way. Progesterone on the other hand increases MMP for joint remodeling, but that's why it's not enough to help joints, either GH or DHEA is needed for the actual anabolic effect (and local IGF-1). Of course joints mainly heal during the night (that's when fat oxidation and carnitine are at their most important), and if I could get my youthful GH spike back, I would certainly do that, but in the meantime, DHEA seems to be the best stand-in. DHEA also is more forgiving for eating closer to bedtime. In one or two ways it's almost like the "resource abundance" growth hormone but that's stretching it. The day after I take DHEA + progesterone my stress levels are flat and my brain behaves more similar to the way it does on THC, but with a more relaxed, social and loving character, though I can also reach that more dramatically with varying combinations of supplements + THC. Since progesterone upregulates CB1 that would seem to liken them, and NMDA is likely involved (I also tried sarcosine with THC and there's something there), but there's probably more to that story. So I kinda ditched the topic of sarcosine for the time being, yet it was more important than I realized.
     
  18. Goobz

    Goobz Member

    Joined:
    Mar 2, 2019
    Messages:
    302
    Gender:
    Male
    Location:
    Australia
    Thanks for the contribution I might try DHEA at night some time.

    Have you considered low dose lithium or something else to increase deep sleep? If you do that perhaps your GH secretion will improve, since I think that’s mostly released during deep sleep.

    I believe sarcosine may be involved in a very important pathway for me personally, but more of a downstream effect (I think I have issues with kynurenine pathway being activated)
     
  19. LeeLemonoil

    LeeLemonoil Member

    Joined:
    Sep 24, 2016
    Messages:
    2,026
    Gender:
    Male
  20. OP
    Terma

    Terma Member

    Joined:
    May 8, 2017
    Messages:
    1,062
    Gender:
    Male
    Yes I did try lithium orotate, but in doses >= 1mg I can only handle it for one day at time (500mcg or less is fine but not very noticeable). I had conflicting information on that one (e.g. Paul Jaminet said it needed to be taken in the morning). Iirc it delays sleep phase, at the time was the opposite of what I needed.

    Kynurenine gets messed up in many disease, but it's the same dilemma of up vs downstream. I'm certain I have issues with that too. Though I suspect dynorphin as much or more.

    Exactly I wanted Baclofen for that, but couldn't get it. Those are the regular preformed GABA supplements? That's a little surprising, I might try it when I get a chance, thanks. I tried them years ago.