Ray Peat Email Advice Depository Discussion/Comment Thread

milk_lover

Member
Joined
Aug 15, 2015
Messages
1,909
What sort of things do you experience with glycine and gelatin?
I am very confused when it comes to glycine/gelatin. I have a love hate relationship with this substance. Sometimes it works like a charm and sometimes it makes me retain water in my body. One thing I like about it is that it gives me nice skin and hair.

I am trying as of now to make it work for me 100%. Doing different experiments the past few weeks. I can't give up on glycine/gelatin because I feel it's very important in my life given how much muscle meat I eat almost daily.
 

Koveras

Member
Joined
Dec 17, 2015
Messages
720
I am very confused when it comes to glycine/gelatin. I have a love hate relationship with this substance. Sometimes it works like a charm and sometimes it makes me retain water in my body. One thing I like about it is that it gives me nice skin and hair.

I am trying as of now to make it work for me 100%. Doing different experiments the past few weeks. I can't give up on glycine/gelatin because I feel it's very important in my life given how much muscle meat I eat almost daily.

I had my own set of issues from glycine & gelatin

Researching glycine encephalopathy and the glycine cleavage system was helpful

There are several genes involved in producing enzymes necessary for the metabolism of glycine:

GLDC - encodes the P-protein (glycine dehydrogenase)
GCST/AMT - encodes the T-protein (aminomethyltransferase)
GCSH - encodes the H-protein
GCSL/DLD - encodes the L-protein (dihydrolipoyl dehydrogenase)

While the typical "mutations" in the glycine cleavage system cause some fairly severe issues (presenting in infancy), it's possible to have polymorphisms in those genes that reduce the efficacy of the system somewhat. There are many cofactors as well so genetics involved in those could also be related.

The direct cofactors to the system I noted:

Vitamin B9/Folate
NAD+ (via Vitamin B3/Niacinamide)
FAD (via Vitamin B2/Riboflavin)
Vitamin B6/Pyridoxal
Lipoic Acid
Ubiquinone/Coenzyme Q10

Anyway not necessarily your issue but I thought I would put that out there - always possible some transient nutrient deficiency or other burdens on the system could slow things down.
 

milk_lover

Member
Joined
Aug 15, 2015
Messages
1,909
I had my own set of issues from glycine & gelatin

Researching glycine encephalopathy and the glycine cleavage system was helpful

There are several genes involved in producing enzymes necessary for the metabolism of glycine:

GLDC - encodes the P-protein (glycine dehydrogenase)
GCST/AMT - encodes the T-protein (aminomethyltransferase)
GCSH - encodes the H-protein
GCSL/DLD - encodes the L-protein (dihydrolipoyl dehydrogenase)

While the typical "mutations" in the glycine cleavage system cause some fairly severe issues (presenting in infancy), it's possible to have polymorphisms in those genes that reduce the efficacy of the system somewhat. There are many cofactors as well so genetics involved in those could also be related.

The direct cofactors to the system I noted:

Vitamin B9/Folate
NAD+ (via Vitamin B3/Niacinamide)
FAD (via Vitamin B2/Riboflavin)
Vitamin B6/Pyridoxal
Lipoic Acid
Ubiquinone/Coenzyme Q10

Anyway not necessarily your issue but I thought I would put that out there - always possible some transient nutrient deficiency or other burdens on the system could slow things down.
Thanks for the info. This might be my issue when taking g;ycine. It might be due to a deficiency as you pointed. Any good advice you have to those who don't react to glycine that well?
 

Koveras

Member
Joined
Dec 17, 2015
Messages
720
Thanks for the info. This might be my issue when taking g;ycine. It might be due to a deficiency as you pointed. Any good advice you have to those who don't react to glycine that well?

Only to experiment.

Looking for the individual polymorphism might give a slightly more directed approach but otherwise one could just experiment with the cofactors.

I already supplemented with B2, B3, and B6 so I decided to try R-lipoic acid and folic acid. They definitely seemed to resolve some issues I was having with bone broth.

I won't take either regularly because of the potential issues with folic acid and maybe some other issues with lipoic acid (and the cost) - but they're probably things I'll keep on hand for meals that might be heavier in glycine.
 

milk_lover

Member
Joined
Aug 15, 2015
Messages
1,909
Only to experiment.

Looking for the individual polymorphism might give a slightly more directed approach but otherwise one could just experiment with the cofactors.

I already supplemented with B2, B3, and B6 so I decided to try R-lipoic acid and folic acid. They definitely seemed to resolve some issues I was having with bone broth.

I won't take either regularly because of the potential issues with folic acid and maybe some other issues with lipoic acid (and the cost) - but they're probably things I'll keep on hand for meals that might be heavier in glycine.
Thanks. I also read somewhere on the forum that pregnenolone helps open glycine channel or something. So maybe taking pregnenolone with the glycine source might be a good experiment to do.
 

sladerunner69

Member
Joined
May 24, 2013
Messages
3,307
Age
31
Location
Los Angeles
In regard to supplementing thyroid when having an irregular interval of stress, such as with a 9-5 or school schedule:

With 5 days of work stress, would the T4 cause hyperthyroidism on the weekends when stress is lower, or would you recommend T3-only to combat the stress (I know you don't usually)?

"I think a combination or natural thyroid such as Thyrolar, Cynoplus, or Armour is usually best. A basic antistress action of thyroid is to convert cholesterol into pregnenolone, progesterone, and DHEA, but that requires adequate cholesterol, and a good mixed diet helps to maintain that."

Side stepping the question, maybe Ray should get into politics next.

Just kidding, I think its up to the person to dial in their correct dosages maybe skip the t4 on the weekends and use t3 as needed, if your pulse is too high.
 

DaveFoster

Member
Joined
Jul 23, 2015
Messages
5,027
Location
Portland, Oregon
Side stepping the question, maybe Ray should get into politics next.

Just kidding, I think its up to the person to dial in their correct dosages maybe skip the t4 on the weekends and use t3 as needed, if your pulse is too high.
I did think that was a little odd. He must not think that it matters very much.
 

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
Asked Ray about St John's wort, got an interesting reply;

I still would not take extract of the whole plant. It has been proven to cause serotonin syndrome in people. The hyperforin does have some pretty interesting properties. No wonder Peat is interested in it. The SIRT inhibition is especially interesting as there are very few chemical that have that functionality. But I am not very keen on its cholinergic, glutamatergic and GABA antagonism effects. I guess you can't get everything good and none of the bad...
Hyperforin - Wikipedia
"...Hyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort.[13] It acts as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, and of GABA and glutamate, with IC50 values of 0.05-0.10 μg/mL for all compounds, with the exception of glutamate, which is in the 0.5 μg/mL range.[14] Hyperforin also inhibits the reuptake of glycine[15] and choline (IC50=8.5μM).[16] It also modulates acetylcholine release in rat hippocampus and facilitates acetylcholine release in the striatum.[17][18] It appears to exert these effects by activating the transient receptor potential ion channel TRPC6.[19] Activation of TRPC6 induces the entry of sodium and calcium into the cell which causes inhibition of monoamine reuptake.[19] It also antagonises the NMDA receptor, AMPA receptor and GABA receptors.[20][21]

It inhibits TRPC6-degradation.[22] Its action on the TRPC6 cation channel is also believed to be responsible for its BDNF-like modulation of dendritic spine morphology in hippocampal pyramidal neurons.[23]

Nootropic effects of hyperforin have been observed in rats.[12] There is in vivo evidence that it can reduce biomarkers of Alzheimer's Disease in animal models and in vitro,[20][24] an action it seems to share with its analogue, tetrahydrohyperforin.[25][26][27] Hyperforin promotes mitochondrial function and the development of oligodendrocytes.[28]

Hyperforin also induces cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor (PXR).[29] The induction of CYP3A caused by hypericum perforatum seems to be heavily dependent on its hyperforin content.[30]

Hyperforin has been found to be a potent inhibitor of COX-1 and 5-LO with IC50 values of 300nM and 90nM respectively, approximately 3-18 times stronger than aspirin.[31]

Hyperforin is active against methicillin-resistant strains of Staphylococcus aureus (MRSA) with a minimal inhibitory concentration (MIC) value of 1.0 μg/mL (1.86μM),[32] as well as against other gram-positive bacteria.[33]Chemical analogues of hyperforin have also exhibited in vitro activity against various bacterial species.[34] Hyperforin also has the ability to kill Plasmodium falciparum in vitro .[35]

Hyperforin also has anticancer effects in vitro and in vivo, which are likely the result of both its anti-angiogenic and pro-apoptotic effects,[36] and potentially anticlastogenic effect.[37] Several chemical analogues of hyperforin have also exhibited anticancer effects in vitro and in vivo.[38][39][40] Hyperforin also inhibits SIRT1 and SIRT2 with a IC50 of 15±0.5μM and 28±0.2μM respectively.[41]"
 

Regina

Member
Joined
Aug 17, 2016
Messages
6,511
Location
Chicago
I still would not take extract of the whole plant. It has been proven to cause serotonin syndrome in people. The hyperforin does have some pretty interesting properties. No wonder Peat is interested in it. The SIRT inhibition is especially interesting as there are very few chemical that have that functionality. But I am not very keen on its cholinergic, glutamatergic and GABA antagonism effects. I guess you can't get everything good and none of the bad...
Hyperforin - Wikipedia
"...Hyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort.[13] It acts as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, and of GABA and glutamate, with IC50 values of 0.05-0.10 μg/mL for all compounds, with the exception of glutamate, which is in the 0.5 μg/mL range.[14] Hyperforin also inhibits the reuptake of glycine[15] and choline (IC50=8.5μM).[16] It also modulates acetylcholine release in rat hippocampus and facilitates acetylcholine release in the striatum.[17][18] It appears to exert these effects by activating the transient receptor potential ion channel TRPC6.[19] Activation of TRPC6 induces the entry of sodium and calcium into the cell which causes inhibition of monoamine reuptake.[19] It also antagonises the NMDA receptor, AMPA receptor and GABA receptors.[20][21]

It inhibits TRPC6-degradation.[22] Its action on the TRPC6 cation channel is also believed to be responsible for its BDNF-like modulation of dendritic spine morphology in hippocampal pyramidal neurons.[23]

Nootropic effects of hyperforin have been observed in rats.[12] There is in vivo evidence that it can reduce biomarkers of Alzheimer's Disease in animal models and in vitro,[20][24] an action it seems to share with its analogue, tetrahydrohyperforin.[25][26][27] Hyperforin promotes mitochondrial function and the development of oligodendrocytes.[28]

Hyperforin also induces cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor (PXR).[29] The induction of CYP3A caused by hypericum perforatum seems to be heavily dependent on its hyperforin content.[30]

Hyperforin has been found to be a potent inhibitor of COX-1 and 5-LO with IC50 values of 300nM and 90nM respectively, approximately 3-18 times stronger than aspirin.[31]

Hyperforin is active against methicillin-resistant strains of Staphylococcus aureus (MRSA) with a minimal inhibitory concentration (MIC) value of 1.0 μg/mL (1.86μM),[32] as well as against other gram-positive bacteria.[33]Chemical analogues of hyperforin have also exhibited in vitro activity against various bacterial species.[34] Hyperforin also has the ability to kill Plasmodium falciparum in vitro .[35]

Hyperforin also has anticancer effects in vitro and in vivo, which are likely the result of both its anti-angiogenic and pro-apoptotic effects,[36] and potentially anticlastogenic effect.[37] Several chemical analogues of hyperforin have also exhibited anticancer effects in vitro and in vivo.[38][39][40] Hyperforin also inhibits SIRT1 and SIRT2 with a IC50 of 15±0.5μM and 28±0.2μM respectively.[41]"
Just as an example, my dog experienced blindness is one dose of St. John's Wart tincture. It was recommended by my holistic Vet for his anxiety. It took a week before he would go outside during the day again.
 

Drareg

Member
Joined
Feb 18, 2016
Messages
4,772
Just as an example, my dog experienced blindness is one dose of St. John's Wart tincture. It was recommended by my holistic Vet for his anxiety. It took a week before he would go outside during the day again.

Have you tried lowering its serotonin since? I think it was mentioned on here somewhere before about dogs and high serotonin.
 

Regina

Member
Joined
Aug 17, 2016
Messages
6,511
Location
Chicago
Have you tried lowering its serotonin since? I think it was mentioned on here somewhere before about dogs and high serotonin.
For sure, that was my dog's (Mr. Phineas) issue. In the shelter he had black eyes (huge pupils) with blood red whites and was raging away in the cage. That's when I knew I had to have him. LOL
Seriously though, he has taught me a lot. Took me years and probably 10's of 1000's of $$$ with oh so many Vets to learn that it is the serotonin stupid. I just had to find Peat and this forum.
Yes, a couple drops of cyproheptidine and he turns into a golden retriever.
 

Xisca

Member
Joined
Mar 30, 2015
Messages
2,273
Location
Canary Spain
Last edited:

DaveFoster

Member
Joined
Jul 23, 2015
Messages
5,027
Location
Portland, Oregon
Q. Do you eat fibers (carrot/mushrrom/bamboo) alone or with other foods? Does adding other foods negate the beneficial effects of the fibers?
"the intestine makes appropriate adjustments when the diet is consistent." That's pretty neat! More detail on that would be nice.
 

Peatit

Member
Joined
Apr 17, 2015
Messages
181
Location
France
I'm posting this since Ray Peat is recommending an antihistamine (ketotifen)that, as far as I know, is new in his recommendations.

"Have you tried other types of antihistamine, such as ketotifen, diphenhydramine, or cyproheptadine?"

In which context was he recommending ketotifen? It seems that it doesn't have the anticholinergic action of the two others.
 

HDD

Member
Joined
Nov 1, 2012
Messages
2,075
In which context was he recommending ketotifen? It seems that it doesn't have the anticholinergic action of the two others.

I had asked if increased irritability and symptoms were from taking famotidine or from the addition of Cynoplus.

He also suggested small amounts of coffee for the nerve steadying effect.
 

Optimus

Member
Joined
May 6, 2017
Messages
61
Ray peat
Every tissue of the body that has been tested for it has the enzymes needed to metabolize thyroxine; toxins, such as lipid peroxides, can affect some tissues more than others, making a T3 supplement more valuable for them

Does it mean that topically thyroxine (t4) is suitable for normal subjects without toxins? And that t3 wouldn't is unnecessary? What concentration.
 

Similar threads

Back
Top Bottom