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

[jyb]

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.

You could say the same about almost any supplement, including glycine, thyroid, and sadly even food... If it were a cure, none of us would have any metabolic problem and it would all be ancient history by now. But I am open to the idea that magnesium could be just as a powerful bandaid as other good supplements or hormones, yet cheap and simple. I find it to be calming in the same sort of way as light, cyproheptadine, progesterone,...

 

[haidut]

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.

Magnesium is one of the most potent NMDA antagonists, very similar in action to ketamine. Google "ketamine depression" and you will see the mechanism of action explained. So, magnesium likely had more benefit than just restoring magnesium levels, which btw takes months since magnesium is not very well retained in most people.

 

[tara]

and makes I think gallons of bile a day

400-800ml seems to be normal for adults?

 

[dart]

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.



"...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."

Very insightful post. But I have a question:

On many forums/in almost any blogpost that discusses PFS in relation to decreased Allopregnanolone, it is always assumed that Finasteride not only competitively inhibits 5α-R2 (so the conversion from T to DHT) but also inhibits 5α-R1 (conversion from Progesterone to Allopregnanolone).

While its true that in rodents both isoenzymes demonstrate comparable inhibition following Finasteride exposure, in vitro binding studies show that Finasteride has a 100-fold selectivity for 5α-R2 over 5α-R1 in humans (A new look at the 5alpha-reductase inhibitor finasteride. - PubMed - NCBI).

So how good is our basis to discuss the adverse effects of Finasteride on ALLO and inhibitory activity on GABA-A really?

 

[haidut]

Very insightful post. But I have a question:

On many forums/in almost any blogpost that discusses PFS in relation to decreased Allopregnanolone, it is always assumed that Finasteride not only competitively inhibits 5α-R2 (so the conversion from T to DHT) but also inhibits 5α-R1 (conversion from Progesterone to Allopregnanolone).

While its true that in rodents both isoenzymes demonstrate comparable inhibition following Finasteride exposure, in vitro binding studies show that Finasteride has a 100-fold selectivity for 5α-R2 over 5α-R1 in humans (A new look at the 5alpha-reductase inhibitor finasteride. - PubMed - NCBI).

So how good is our basis to discuss the adverse effects of Finasteride on ALLO and inhibitory activity on GABA-A really?

There have been post-mortem studies on people taking Finasteride and committing suicide due to depression. They all had very low ALLO levels. Studies on brains of people not taking Finasteride also showed lower levels but order of magnitude higher than the ones taking Finasteride. Finally, recent study found that one of the SSRI that managed to reverse PFS (in rodents) did this by dramatically increasing ALLO in brain back to control levels. So, I think Finasteride lowering ALLO is pretty widely acknowledged, even in pharma circles. Finasteride has other bad side effects - it is estrogenic and carcinogenic for the liver, so there may very well be other toxic side effects that contribute to development of PFS beyond its effects on ALLO, but getting ALLO back to normal levels definitely won't hurt.

 

[Kitridge30]

Hi haidut. This is all very interesting. Going back to Glycine. By upregulating 5ar do you think it is possible to unbind the inhibitor put on by saw palmetto? What is the diference between a steriodal inhibitor and a non steriodal inhibitor. Reversible and non reversible? ALLO stand for and hiw do i bring that up?

 

[Ashoka]

Maybe important to mention - progesterone has been one of the most successful treatments for finasteride symptoms.

haidut, what might be some considerations in treating PFS? I know your thoughts about the subject have probably changed a bit over the last couple of years.

 

[natedawggh]

Unintentionally I once took glycine and eggshell calcium at the same time and got so sick I nearly had to go to the hospital. Unlike taurine, pure glycine can form compounds in the stomach with other elements so in my experience care should be taken not to consume free glycine with things that can react with it in the presence of stomach acid.

Your post made me wonder if my stint supplementing glycine had something to do with my hair regrowth, which hasn't been as robust since.

 

[aarfai]

Maybe important to mention - progesterone has been one of the most successful treatments for finasteride symptoms.

haidut, what might be some considerations in treating PFS? I know your thoughts about the subject have probably changed a bit over the last couple of years.

Hey Ashoka at what does progesterone clear up finasteride symptoms? What is your experience using progesterone for this matter? I'm curious because from my understanding progesterone is a 5-alpha-reductase inhibitor and more of a "female" hormone.

Thank you

 

[Ashoka]

Hey Ashoka at what does progesterone clear up finasteride symptoms? What is your experience using progesterone for this matter? I'm curious because from my understanding progesterone is a 5-alpha-reductase inhibitor and more of a "female" hormone.

Thank you

I've never used it. I felt that if I use something like that I have to be prepared for the consequences good or bad and be in a prepared mental space. Basically viewing any one thing as a cure, putting all one's eggs in one basket, isn't the right strategy. I noticed many people with PFS who used and had success with progesterone had a positive attitude and had already seen improvement through diet, exercise, and behavioral changes.

haidut posted this Oral progesterone increases testosterone and DHT a while back. I think this is fairly well known now. I visited an alternative health doctor in Florida and mentioned that people with finasteride symptoms benefit from progesterone. She was aware of the connection between it and raising T and DHT.

 

[haidut]

Hi haidut. This is all very interesting. Going back to Glycine. By upregulating 5ar do you think it is possible to unbind the inhibitor put on by saw palmetto? What is the diference between a steriodal inhibitor and a non steriodal inhibitor. Reversible and non reversible? ALLO stand for and hiw do i bring that up?

Steroidal inhibitor is usually a chemical with structure similar to a steroid which an enzyme may use as a substrtate. Exemestane is a steroidal aromatase inhibitor and if you look at its structure it is very similar to androstenedione and testosterone, which are two substrates for aromatase. Anyways, glycine, pregnenolone, progesterone, and DHEA should all be able to upregulate 5-AR activity. I don't think finasteride is a suicide inhibitor of 5-AR, but even if it was these substances should be able to help. Saw palmetto is much weaker than finasteride and any effects on lowering libido are probably due to the fact that it contains a natural progesterone-type steroid, not so much due to its inhbition of 5-AR. Either way, again the substances I mentioned should help.

 

[haidut]

Maybe important to mention - progesterone has been one of the most successful treatments for finasteride symptoms.

haidut, what might be some considerations in treating PFS? I know your thoughts about the subject have probably changed a bit over the last couple of years.

Keeping thyroid function high so that if actual levels of the 5-AR enzyme are low they can be brought back up. Activity of 5-AR can be upregulated by DHEA, glycine, pregnenolone and even progesterone. Estrogen can also have anti 5-AR activity so opposing estrogen with things like aspirin or vitamin E can also help indirectly.

 

[TubZy]

I can attest to this thread very much. After reading this a week ago, I've decided to add 5 grams of glycine, 5 grams taurine to my black coffee before the gym and I must say my mood boost is incredible. Like haidut said each of those compounds (caffeine/glycine/taurine) increase 5AR along with the correlated neurosteroids.

I want to add pure niacinimide powder to it as well, but I'm still waiting for it to come in. Has anyone else tried this combination?

 

[Wagner83]

If I order taurine and glycine I'll use nutrabio!

 

[ecstatichamster]

I would very much suggest taking collagen and gelatin rather than glycine. Real food always beats isolated amino's with unknown impurities.

 

[amethyst]

I would very much suggest taking collagen and gelatin rather than glycine. Real food always beats isolated amino's with unknown impurities.

I think I'm going to have to do this- switch from Glycine to gelatin. The glycine I think, is giving me a stuffy nose. I read one of the side effects is that is can cause allergy symptoms in some people. That's the only thing I think might be causing my stuffy nose.

 

[Pet Peeve]

I took 16 grams of glycine on an empty stomach with eight drops of progestene on the arm at about the same time. I think I haven't felt this good in years.

 

[Wagner83]

Are you a male?

 

[Dante]

Finally, recent study found that one of the SSRI that managed to reverse PFS (in rodents) did this by dramatically increasing ALLO in brain back to control levels. So, I think Finasteride lowering ALLO is pretty widely acknowledged, even in pharma circles. Finasteride has other bad side effects - it is estrogenic and carcinogenic for the liver, so there may very well be other toxic side effects that contribute to development of PFS beyond its effects on ALLO, but getting ALLO back to normal levels definitely won't hurt.

Yeah , i read in a pfs forum that a poster cured his pfs by taking low dose prozac.
Now , here is something interesting. I also read there that an MD got pfs like symptoms by taking Accutane and that doc cured it by taking finasteride !! ( since i don't do drugs,alcohol so i am sure i was not high while reading that). How is that even possible ? (I guess there was some study showing that after fin intake , there were strongly upregulated androgen receptors and if you get pfs and survive it, , it's like you will hit a second puberty). Any ideas ?

Regarding fin and liver toxicity, i think they showed that dut was toxic, carcinogenic to the liver by inhibition of all 3 forms of 5-AR enzymes while fin was not. ( i might be wrong here though)

 

[Pet Peeve]

Are you a male?

Yes