Glycine Strongly Upregulates 5-alpha Reductase (5-ar) Activity

Discussion in 'Scientific Studies' started by haidut, Jan 25, 2016.

  1. haidut

    haidut Member

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    This is study is a great find in my opinion. It is well known that conditions like depression and dementia are associated with reduced levels of the neurosteroid allopregnanolone. A few of the successful SSRI drugs like Prozac have the "side effect" of increasing levels of allopregnanolone in the brain. Several other drugs that increase brain levels of allopregnanolone are currently in clinical trials for depression, dementia, anxiety, and even schizophrenia. Furthermore, allopregnanolone is capable of increasing metabolism by activating the bile acid "receptor" as described in this thread.
    How Pregnenolone And Progesterone Raise Metabolism | Ray Peat Forum

    On the flip side, drugs like Finasteride and some other anti-androgens lower allopreganolone by inhibiting 5-AR. All in all, raising levels of allopregnanolone appears to be highly beneficial and lowering its levels can lead to everything from depression to the dreaded post-Finasteride syndrome.

    Allopregnanolone is a steroid derived from progesterone through the action of the enzyme 5-AR. Another steroid derived through the activity of 5-AR is of course DHT. DHT also has strong anti-depressant and pro-metabolic effects. Furthermore, upregulated 5-AR helps with deactivation and excretion of cortisol and estrogen.
    This study found that even physiological concentrations of glycine both raised levels of allopreganolone in the brain AND upregulated activity of 5-AR. If true, this immediately makes glycine a potent, dirt-cheap OTC anti-depressant and a powerful androgenic stimulator. Considering the effects of other amino acids like taurine on steroidogenesis, a combination of glycine and taurine would be a great way to upregulate sagging steroid production (especially in the brain), while simultaneously lowering estrogen and cortisol. I know some people here also cross-post on the hair loss and post-Finasteride forums, so it would be good to see what folks over there think about that as well.

    Regulation of neurosteroid allopregnanolone biosynthesis in the rat spinal cord by glycine and the alkaloidal analogs strychnine and gelsemine. - PubMed - NCBI

    "...But concerning glycine, no report had until now investigated the possible control of neurosteroid biosynthesis, particularly 3,5-THP secretion, by pharmacological agents of the glycinergic system. Therefore, the present work constitutes the first demonstration indicating that glycine, acting through Gly-R, stimulates 3,5-THP production in the rat SC. Applications of graded micromolar concentrations of glycine generally involved in glycinergic neurotransmission (Legendre, 2001; Kirsch, 2006) induced a dose-dependent increase of 3,5-THP biosynthesis in the rat SC. Furthermore, this paper also shows that gelsemine, a structural analog of strychnine, is a positive regulator of 3,5-THP formation in the SC."


    "...Therefore, it appears that the chloride ion influx induced by glycine or gelsemine via Gly-R activation may indirectly cause an intracellular pH modification allowing the stimulation of 5-reductase and/or 3-HSOR activity in spinal nerve cells. In support of this hypothesis, we observed that at certain concentrations (1 uM and 35 uM), glycine strongly enhanced 5-reductase activity leading to increased amounts of [3H]5-DHP. Other concentrations of glycine (70 uM and 140 uM) mainly accelerated 3-HSOR activity and the elevated speed of 3-HSOR enzymatic reaction generating high amounts of [3H]3,5-THP did not allow identification of the transient increase of the intermediate steroid ([3H]5-DHP) level 3 h after the incorporation of [3H]PROG into SC slices."

    "...Glycine and the neurosteroid 3,5-THP are known to regulate several important neurophysiological processes such as pain and anxiety (Akwa et al., 1999; Patte-Mensah et al., 2004a, 2005, 2006; Zeilhofer, 2005; McCool and Chappell, 2007; Pellicer et al., 2007). The neuroactive steroid 5-DHP also exhibited neuroprotective properties in various experimental models (for review, Roglio et al., 2007). Therefore, even though further studies are required to specify gelsemine effects in vivo, the fact that gelsemine exerts a potent stimulatory action on 5-DHP and 3,5-THP biosynthesis suggests that gelsemine and medicine produced from Gelsemium sempervirens may be interesting compounds to investigate for therapies of neuropathological disorders evoked by disturbances of the central inhibitory transmission."

    Now of course everybody wants to know what dose of glycine would have that effect. The study shows that the effective glycine concentrations were in the range 1 uM - 35 uM. The glycine concentrations in the brain are about 100 times lower than in plasma. This means, a plasma concentration in the range 100uM - 3,500uM is needed. As I posted in another study on glycine below, an oral dose of 4.6g glycine achieves about 900uM, so for simplicity let's say 5g achieves 1,000uM (1mM).
    Aging in human mitochondria fully reversed by glycine | Ray Peat Forum

    This mean that oral glycine doses in the range of 500mg - 16g are needed to achieve the effective concentration in the brain. The effect is dose-dependent, so the higher the glycine dose the more effective it is on allopregnanolone and 5-AR activity. Now, taurine seems to upregulate the rest of the steroidogenic pathways as the study below indicate.
    Taurine increases testicular function in aged rats by inhibiting oxidative stress and apoptosis. - PubMed - NCBI
    Taurine reverses endosulfan-induced oxidative stress and apoptosis in adult rat testis. - PubMed - NCBI

    If glycine indeed upregulates 5-AR then combining glycine with taurine and adding DHEA/pregnenolone (if needed) should have a dramatic positive effect on mental health, cognition, and steroid profile that are so negatively affected by hypothyroidism and aging in general.

    Furthermore, in light of the ability of niacinamide to lower cortisol, oppose estrogen, and increase androgenic expression and DHT signalling, adding niacinamide to the glycine/DHEA combo should make it even more potent.
    Niacinamide Is Androgenic And Increases Dht Effects/signaling | Ray Peat Forum
    Niacinamide Is Anti-estrogenic | Ray Peat Forum
    Niacinamide Lowers Cortisol | Ray Peat Forum
     
  2. milk_lover

    milk_lover Member

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    Interesting! Thanks for posting this, haidut. No wonder shrimp and seafood in general are famous for inducing libido in males. AFAIK, they contain glycine and taurine. The amino acid balancing act is the best thing a person can do to reach good health faster.

    This is a good reminder not to give up on gelatin. The glycine supplements in our market have bad additives like silica and Microcrystalline cellulose, unfortunately.
     
  3. brandonk

    brandonk Member

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    I've looked into isolated amino acids and been disappointed by what I've found, especially for taurine. Literally a ton of taurine is made in China in about 4,000 mostly uninspected facilities, and extremely cheap, and is often used to adulterate pet food and casein powders.

    Worse yet, the manufacturing process is so poor that it leaves the resulting crystals impossible to metabolize, so that the entire amount ingested is fully excreted in the urine over seven days.

    If you consider Ray Peat's concerns about the manufacturing process for isolating amino acids, using sulfurous acid or ethanolamine, I think there are also very real safety concerns with taurine.

    Ray Peat has never mentioned a need to supplement taurine (that I've seen), and the body makes taurine from methionine and cysteine, and then conjugates it with bile acid, and makes I think gallons of bile a day, and recycles it. So taurine in the diet hardly compares to the amount that the body produces for conjugating with bile.

    Glycine, on the other hand, is needed in relatively large quantities. And so to your point, milklover, I agree that high-quality gelatin and collagen are excellent sources of truly available glycine.

    Ray Peat has specifically said not to take glycine as a supplement for more than a few days, and to use gelatin or collagen instead.
     
  4. charlie

    charlie The Law & Order Admin

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    Taurine has worked wonders for people in my family. Darn that china helping my family so much. ;)

    Great stuff as always haidut! :)
     
  5. Tarmander

    Tarmander Member

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    I love Taurine. Fantastic stuff and I do indeed use it with small amounts of your topical DHEA and Preg. I have used glycine before as a stand alone amino acid. My only concern with it is that it seemed to suppress my immune system. I believe I read one time that glycine suppresses a certain type of inflammation that your immune system uses. I would be interested to hear if others have had this issue with Glycine.

    Edit: Here is the Study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665071/

    " Glycine has inhibitory effects on immune cells, including macrophages, monocytes, neutrophils and lymphocytes."
     
  6. hmac

    hmac Member

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    Amazing!

    Makes me think magnesium glycinate is probably an incredibly effective anti-depressant
     
  7. OP
    haidut

    haidut Member

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    It is indeed, together with magnesium taurate. Both cured major depression in humans in as little as 1 week.
    http://www.ncbi.nlm.nih.gov/pubmed/16542786
    "...Case histories are presented showing rapid recovery (less than 7 days) from major depression using 125-300 mg of magnesium (as glycinate and taurinate) with each meal and at bedtime. Magnesium was found usually effective for treatment of depression in general use. Related and accompanying mental illnesses in these case histories including traumatic brain injury, headache, suicidal ideation, anxiety, irritability, insomnia, postpartum depression, cocaine, alcohol and tobacco abuse, hypersensitivity to calcium, short-term memory loss and IQ loss were also benefited. Dietary deficiencies of magnesium, coupled with excess calcium and stress may cause many cases of other related symptoms including agitation, anxiety, irritability, confusion, asthenia, sleeplessness, headache, delirium, hallucinations and hyperexcitability, with each of these having been previously documented."
     
  8. Parsifal

    Parsifal Member

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    Where did Ray said that?
     
  9. mujuro

    mujuro Member

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    How about sublingual glycine? Would that be better to achieve a higher plasma level with less actual glycine?

    This is just a hypothetical, because I have heard that sublingual glycine can be used to abort a panic attack.
     
  10. DaveFoster

    DaveFoster Member

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    Do you think that 16 g of supplemental glycine daily is sustainable indefinitely with no ill effects?
     
  11. OP
    haidut

    haidut Member

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    IF (and it is a big IF, pun intended) it is pure then I don't see any problem with it except for people with kidney disease. Doses used for conditions like schizophrenia are in the range of 80g daily for 12 months and have no side effects. Here is the quote from Peat:
    http://raypeat.com/articles/articles/gelatin.shtml
    "...It has a wide range of antitumor actions, including the inhibition of new blood vessel formation (angiogenesis), and it has shown protective activity in liver cancer and melanoma. Since glycine is non-toxic (if the kidneys are working, since any amino acid will contribute to the production of ammonia), this kind of chemotherapy can be pleasant."
     
  12. aguilaroja

    aguilaroja Member

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    http://www.ncbi.nlm.nih.gov/pubmed/16542786

    There have been repeated citations on the forum of George Eby's article (on magnesium) in the journal "Medical Hypotheses". On a PubMed search, "Medical Hypotheses" is the only journal where Mr. Eby has been published.

    It is encouraged to look at his website for more context, http://george-eby-research.com/

    http://george-eby-research.com/html/depression-anxiety.html#dep

    There are some interesting ideas on the web pages, that somewhat match ideas discussed on the RP forum. Also, there are some topics where Eby's views appear to differ markedly from Dr. Peat's expressed views.

    Clearly, readers of this site are open-minded about independent researchers' conclusions. At the same time, Mr. Eby, in describing case reports, and publishing only in a journal by title devoted to hypotheses, is pursuing a path with different adjudication than most of the researchers indexed on PubMed, or cited in this forum.
     
  13. sladerunner69

    sladerunner69 Member

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    Is there significant amounts of glycine in gelatin and pork rinds? I don't feel a very pronounced effect when eating those foods but I do after eating shellfish, whcih have high selenium and taurines.
     
  14. Makrosky

    Makrosky Member

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    *only* 35% of the aminoacids of geltain is glycine ;-) So if you take 13 grams you're getting 4,5 grams at once. Not bad. Don't know about the pork rinds.

    Shellfish also have zinc, copper, manganese, iodine... I don't understand why are you comparing gelatin and pork rinds with shellfish.
     
  15. Makrosky

    Makrosky Member

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    I think those people were not depressed (which I think it's a very compelx issue), they were just extremely deficient in magnesium. If magnesium would be such an effective cure for depression, it would be well known and used, and it is not. I'm not saying magnesium doesn't help with depression, I think it does indeed. But Eby's claims are way exaggerated. IIRC the n of the study was 8. The authors are just Eby and his wife. And the "n" were people close to them IIRC. No double-blinded. No placebo controlled. And they are not MD's, ND's, or have any scientific credentials to design experiments with a minimum degree of reliability. And besides that, my anecdotal experience and that of a few people I know that tried magnesium is that it helps to alleviate anxiety and stuff but doesn't cure depression. I don't even know how this "paper" made its way to pubmed.

    I'm sure you agree haidut that "depression" is a vague term including lots of sociocultural/biochemical issues. How in hell is it possible that people get cured or symptomatically relieved from a single illness depresion with such different cures like all sorts of psychotherapy, changin a life situation, thyroid, aminoacids including tryptophan, bowel and liver cleanses, chinese medicine, removing amalgams, b12 shots, exorcisms, you name it. It must be different illnesses disguised as depression.
     
  16. sladerunner69

    sladerunner69 Member

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    The reason I am comparing gelatin and porkrinds with shellfish is because they both come from the same animal.

    Duh.
     
  17. Makrosky

    Makrosky Member

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    I meant comparing gelatin and porkrinds TO shellfish. Nevermind.
     
  18. sladerunner69

    sladerunner69 Member

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    My original point wasn't exactly succinct, what I meant however, was that gelatin doesn't seem to give me that elusive DHT boost like shellfish does. I am forever seeking the eternal path of DHT increase. And I have much experience and wisdom to share from my jounrey along this road.
     
  19. Nighteyes

    Nighteyes Member

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    Please share your journey and results if you please :) perhaps in a seperate thread. This is one of my great goals as Well. For me eating three oysters at The same time of taking ~1 mg DHEA + 2mg preg seems to do The trick for a short time
     
  20. aarfai

    aarfai Member

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    What other substances do you guys know that upregulates 5-alpha reductase or the androgen receptors? Thank you in advance
     
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