Niacinamide Is Androgenic And Increases Dht Effects/signaling

haidut

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I just posted a study showing that inhibition of SIRT1 is anti-estrogenic, and SIRT1 inhibitors like niacinamide have similar effects to the estrogen receptor antagonist fulvestrant.
Niacinamide Is Anti-estrogenic | Ray Peat Forum

This study shows that, again through inhibition of SIRT1, niacinamide enhances AR expression and effects of the powerful androgen DHT. Given the anti-cortisol effects of niacinamide that I also posted about it seems that niacinamide is one of the most versatile substances that can stop stop the stress response and maybe even reverse the catabolic state. Also, there should be nice synergy with DHEA and glycine to potentiate the androgenic effect even more, given glycine's upregulation of 5-AR.

Glycine Strongly Upregulates 5-alpha Reductase (5-ar) Activity | Ray Peat Forum
Glycine Powerfully Lowers Cortisol | Ray Peat Forum

The androgenic mechanism of action of niacinamide is inhibition of the sirtuins. The EC50 of niacinamide for sirtuin inhibition is 11uM, which in humans is achievable with less then 100mg niacinamide. Interestingly, Hoffer apparently sent somebody recommendations for 1,500mg niacinamide daily being optimal for longevity and health. This is the same dose successfully used in humans for diabetes type II and metabolic syndrome.
Niacinamide and SIRT - what is the minimum dose required for inhibition? - Supplements
"...According to Pubchem, the concentration required for 50% inhibition of SIRT2 is 11uM, although I have no idea how this translates to mg/kg)."

"...Upregulation of SIRT1 may increase lifespan in fruit flies and roundworms, but may actually have detrimental effects in strokes, some types of cancer and dementia, particularly when NAD+ levels are insufficient. The types of cancer in question apparently include prostate cancer and SCLC. The anticancer protocol which the late Abram Hoffer faxed me 16 years ago included 1,500 mg of niacinamide. Inhibition of SIRT1 is apparently one of the pathways in which niacinamide fights cancer."

In summary, the ability of both niacinamide and glycine to lower cortisol, oppose estrogen, and promote androgenic signalling may also make them potential drugs for osteoporosis, depression, PTSD, sarcopenia, stress-induced ulcers, heart disease, hair loss, and even some neurodegenerative conditions like ALS and Huntington that have been shown to benefit from androgenic therapy.


Hormonal control of androgen receptor function through SIRT1. - PubMed - NCBI

"...The NAD-dependent histone deacetylase Sir2 plays a key role in connecting cellular metabolism with gene silencing and aging. The androgen receptor (AR) is a ligand-regulated modular nuclear receptor governing prostate cancer cellular proliferation, differentiation, and apoptosis in response to androgens, including dihydrotestosterone (DHT). Here, SIRT1 antagonists induce endogenous AR expression and enhance DHT-mediated AR expression. SIRT1 binds and deacetylates the AR at a conserved lysine motif. Human SIRT1 (hSIRT1) repression of DHT-induced AR signaling requires the NAD-dependent catalytic function of hSIRT1 and the AR lysine residues deacetylated by SIRT1. SIRT1 inhibited coactivator-induced interactions between the AR amino and carboxyl termini. DHT-induced prostate cancer cellular contact-independent growth is also blocked by SIRT1, providing a direct functional link between the AR, which is a critical determinant of progression of human prostate cancer, and the sirtuins."

"...What might be the significance of the finding that AR expression and DHT signaling are regulated by nicotinamide and NAD-dependent deacetylation? The requirement for NAD in Sir2 enzymatic activity has led to suggestions that Sir2 activity may be regulated by the intracellular concentration of NAD, by the NAD/NADH ratio, or by the intracellular concentration of nicotinamide (2, 35, 36, 45). Endogenous levels of nicotinamide may limit Sir2 activity (49), suggesting that the concentration of nicotinamide in response to physiological changes could affect Sir2 function. Metabolic changes in muscle induced by pyruvate, for example, increase the NAD+/NADH ratio and inhibit muscle gene expression, whereas lactate reduces the NAD/NADH ratio and stimulates muscle gene expression (21). Androgens maintain male muscle mass (10a, 26, 50) and induce muscle cellular gene expression. During prostate cancer progression, metabolism shifts toward cytosolic glycolysis (1, 12). The increased production of lactate that occurs during prostate cancer progression (5, 46) is predicted to inhibit SIRT1 and thereby enhance AR function. A recent study also suggested that global histone modification in prostate tumor tissues, including acetylation of H3K18 and H4 K12, dimethylation of H3K4 and H4R3, and acetylation of H3K9, a target of SirT1 (54), predict a risk of prostate cancer recurrence (51)."

"...Here, SIRT1 inhibited androgen-dependent prostate cancer cellular growth and repressed the endogenous androgen-responsive target gene, AR. AR is an androgen-responsive gene, and sirtinol, a Sir2-specific inhibitor, increased the abundance of acetylated-AR acetylation. Nicotinamide, a noncompetitive inhibitor of Sir2, induced expression of the endogenous androgen-responsive AR gene. The selective chemical inhibitor of SIRT activity, splitomycin, enhanced AR-dependent gene expression, suggesting that endogenous SirT1 contributes to maintenance of the AR in a repressed state.
 
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Gl;itch.e

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Haidut, lately I have added DHEA (2-5mg) into my supplement regime. I currently take it in one dose after training in the evening or with dinner on non training days. I was doing so mostly in an attempt to help with lowering cortisol and enhancing recovery from training (which it seems to be doing). This post of yours makes me think I should add Niacinamide and Glycine back into my regime at the same time. Do you think 500mg Niacinamide and 5g of Glycine would have beneficial synergistic effects? Any other things you think might help synergise with these 3 compounds?
 

haidut

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Haidut, lately I have added DHEA (2-5mg) into my supplement regime. I currently take it in one dose after training in the evening or with dinner on non training days. I was doing so mostly in an attempt to help with lowering cortisol and enhancing recovery from training (which it seems to be doing). This post of yours makes me think I should add Niacinamide and Glycine back into my regime at the same time. Do you think 500mg Niacinamide and 5g of Glycine would have beneficial synergistic effects? Any other things you think might help synergise with these 3 compounds?

I don't think you need 5g glycine for the androgenic effects. The study I posted showed maximum stimulation of 5-AR from about 130uM glycine, which is achievable by 500mg oral glycine. How much niacinamide you need depends on your health state and it seems that it is highly individual, but even 100mg a few times daily should have an effect.
 

Tarmander

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I was reading posts about hair loss on Reddit and I came across one posted on nofap...the author and commentators basically posited that masturbation led to higher levels of DHT which then led to hair loss. This sounded ridiculous because that would mean we could jack our way off to great health through raised DHT levels...which definitely is NOT the case.

But if you follow the logic, then niacinamide would be an anti hair nutrient because of raised DHT levels! We should let those guys know ;)
 

FredSonoma

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I don't think you need 5g glycine for the androgenic effects. The study I posted showed maximum stimulation of 5-AR from about 130uM glycine, which is achievable by 500mg oral glycine. How much niacinamide you need depends on your health state and it seems that it is highly individual, but even 100mg a few times daily should have an effect.
Is it true that it if I have liver problems it might be better to hold off on the niacinamide until my liver problems clear up?
 

haidut

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I was reading posts about hair loss on Reddit and I came across one posted on nofap...the author and commentators basically posited that masturbation led to higher levels of DHT which then led to hair loss. This sounded ridiculous because that would mean we could jack our way off to great health through raised DHT levels...which definitely is NOT the case.

But if you follow the logic, then niacinamide would be an anti hair nutrient because of raised DHT levels! We should let those guys know ;)

Fapping too much will raise prolactin, and should actually contribute to hair loss. So, I guess Reddit is right on the cause (fapping) but not the mechanism (DHT).
 

haidut

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superhuman

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Haidut, lately I have added DHEA (2-5mg) into my supplement regime. I currently take it in one dose after training in the evening or with dinner on non training days. I was doing so mostly in an attempt to help with lowering cortisol and enhancing recovery from training (which it seems to be doing). This post of yours makes me think I should add Niacinamide and Glycine back into my regime at the same time. Do you think 500mg Niacinamide and 5g of Glycine would have beneficial synergistic effects? Any other things you think might help synergise with these 3 compounds?

Isnt it best to take DHEA in the morning when cortisol is highest? together with pregnenolone
 

haidut

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Isnt it best to take DHEA in the morning when cortisol is highest? together with pregnenolone

I think it's best to take in the evening so that it gets a chance to metabolize properly before cortisol starts to rise. Once cortisol is high, DHEA may actually get turned to estrone since cortisol activates aromatase. So, yes, pregnenolone + DHEA is a good idea but probably best taken before stress hormones rise. Once cortisol is high, I'd stick to pure pregnenolone, progesterone, glycine, niacinamide, theanine, etc.
 

superhuman

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I think it's best to take in the evening so that it gets a chance to metabolize properly before cortisol starts to rise. Once cortisol is high, DHEA may actually get turned to estrone since cortisol activates aromatase. So, yes, pregnenolone + DHEA is a good idea but probably best taken before stress hormones rise. Once cortisol is high, I'd stick to pure pregnenolone, progesterone, glycine, niacinamide, theanine, etc.

Thats awesome, thanx
 

Gl;itch.e

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Isnt it best to take DHEA in the morning when cortisol is highest? together with pregnenolone
I think it's best to take in the evening so that it gets a chance to metabolize properly before cortisol starts to rise. Once cortisol is high, DHEA may actually get turned to estrone since cortisol activates aromatase. So, yes, pregnenolone + DHEA is a good idea but probably best taken before stress hormones rise. Once cortisol is high, I'd stick to pure pregnenolone, progesterone, glycine, niacinamide, theanine, etc.
My reasoning is that it is normal to have higher cortisol in the morning and that lowering it when it shouldn't be high (evenings) is more beneficial.
 

superhuman

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My reasoning is that it is normal to have higher cortisol in the morning and that lowering it when it shouldn't be high (evenings) is more beneficial.

We all know that normal does not always mean its good :) the reason its high is because night is high stress. RP told me that the most important time of the day to get sugar is for breakfast to get cortisol and stress down
 

matty

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Quick question for clarification. In the study that uses low dose niacinamide, 3mg/kg, is that a conversion for 3mg per kilogram of body weight? Such that someone weighing 100 pounds would take 135mg niacinamide?
 

haidut

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Quick question for clarification. In the study that uses low dose niacinamide, 3mg/kg, is that a conversion for 3mg per kilogram of body weight? Such that someone weighing 100 pounds would take 135mg niacinamide?

Which study are you referring to? In the original post above I mentioned that the EC50 for sirtuin inhibition is 11uM, which is achievable in humans by taking about 100mg niacinamide.
 

haidut

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tca300

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I don't think you need 5g glycine for the androgenic effects. The study I posted showed maximum stimulation of 5-AR from about 130uM glycine, which is achievable by 500mg oral glycine. How much niacinamide you need depends on your health state and it seems that it is highly individual, but even 100mg a few times daily should have an effect.
In your Glycine strongly upregulates 5-AR thread you said "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. " So 16 grams of Glycine per day has the exact same effect on 5-AR as 500mg?!? Thanks!
 

DaveFoster

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I was reading posts about hair loss on Reddit and I came across one posted on nofap...the author and commentators basically posited that masturbation led to higher levels of DHT which then led to hair loss. This sounded ridiculous because that would mean we could jack our way off to great health through raised DHT levels...which definitely is NOT the case. ;)
I'll come out with a new product: Fapsteride.

It's a combination of finasteride and amphetamine so you can go to town for 8 hours.
 
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