Naringin inhibition of CYP450?

[Right Hook]

D_ in this thread we started to discuss Naringin's inhibition of CYP450 and you made this comment in regards to my post:

Originally Posted by Right Hook

It inhibits cytochrome P450 enzymes. One P450 enzyme is CYP19A....which apparently increases aromatization. So inhibiting P450 enzymes and assuming it is selective to only (and this is probably a big assumption) the CYP19A enzyme then yes it should theoretically work. To what real world extent I have no idea...
.

Originally Posted by dinoiii

CyP19A is another name for aromatase.

Still, the level of inhibition is relatively inconsequential.

D_

My question is whether you were referring to the inhibition of CyP19A (aromatase) or the inhibition of CyP450.....or both?

Reason I ask is that the first step in testosterone synthesis would be the conversion of Cholesterol to Pregnenolone, via CyP450 (CyP450 side chain cleavage to be exact) enzymatic reaction. Therefor it would make me think Naringin would be something one would want to avoid during PCT. Right? Wrong? Way off likely....

Thanks in advance.

[Right Hook]

Btw, not really relevant to my question but the Scivation guys seem up on naringin for its fat loss properties and its ability to enhance/prolong the effects of caffeine. This is taken from The Ultimate Diet book:

Grapefruit—The Great Fruit
We recommend obtaining your carbohydrates in every meal during the Cut Diet
(not including the carbohydrate meal) from leafy green vegetables and grapefruit. Why
grapefruit?
Grapefruit is loaded with naringin. The majority of caffeine and other alkaloids
are metabolized by various enzymes such as CYP1A2, CYP2E1 and CYP3A4. However,
naringin has been documented to inhibit CYP34A (as well as CYP1A2) activity in human
liver. This means that naringin may increase the half life (extending the activity) of
various alkaloids, especially caffeine. Many fat burners utilize naringin for enhanced
alkaloid effect. We got hooked on in it 10-11 years ago in the Cut Diet and since then, we
have never dealt with anything else. We will allow oranges if necessary but they do not
contain as much naringin as grapefruit. So unless you cannot stomach them at all, eat
your grapefruit! We recommend sprinkling a packet or two of Splenda® on them. In a
recent study in La Jolla, CA, grapefruit consumption was found to be associated with a
reduction in weight. Moreover, 2-hour post-glucose insulin levels were significantly
reduced among subjects consuming half a grapefruit with each meal, as compared to a
placebo.

[dinoiii]

[quote=Right Hook;67024]My question is whether you were referring to the inhibition of CyP19A (aromatase) or the inhibition of CyP450.....or both?[quote]

Both, but in all likelihood, you need huge quantities to impact this desmolase system to any large degree.

Reason I ask is that the first step in testosterone synthesis would be the conversion of Cholesterol to Pregnenolone, via CyP450 (CyP450 side chain cleavage to be exact) enzymatic reaction. Therefor it would make me think Naringin would be something one would want to avoid during PCT. Right? Wrong? Way off likely....

Interesting thoughts, that do minimally display steroidogenesis is not as neat and clean as many supplement companies like to portray perhaps. Still steroids derived from Cholesterol (27 carbons) come in different fashions
(1) 80% from LDL
(2) 20% from HDL & Acetate (de novo synthesis)


Subsequently, cholesterol to Pregnenolone (21 carbons) is what is known as the rate limiting step with
(1) Cytochrome P450 Side Chain Cleavage enzyme (desmolase) which you mentioned, but also
(2) Controlled by ACTH, LH, FSH, etc., which are down in immediate post-cycle realms - especially gonadotropins without the use of something like Clomid and/or hCG
(3) This process only occurs in mitochondria

What happens beyond the chol-->preg conversion is divergence of pathways
(1) Glucocorticoids
i. Cortisol
ii. Corticosterone
(2) Mineralocorticoids
i. Aldosterone
(3) Sex Steroids
1. Progestins
(a) pregnenelone
2. Progesterone (w/ interconversion amongst them all)
(a) Androgens
1. Testosterone
2. Androstendione
(b) Estrogens
1. Estradiol
2. Estrone
3. Estriol

The problem is you do not merely have adrenal sourcing alone in solitude. Here's where the imperative level of dosing, serum steady states and HPAA and HPTA crossover mechanisms all interplay. It gets quite complex.

I do think you'd have to ingest huge tallies of this stuff to have any level of impact to be honest with you and over long periods of time. Personally, as my initial post suggested in that other thread, it is likely to be relatively inconsequential in the grand scheme.


D_

[dinoiii]

Keep in mind, each of these adrenal cascades have pertinence in PCT. Mineralocorticoids, Glucocorticoids and Sex Steroids all interplay for a successful PCT in regards to body comp. Only incomplete PCT regimes don't consider that fact.

D_

[Right Hook]

[quote=dinoiii;67082][quote=Right Hook]My question is whether you were referring to the inhibition of CyP19A (aromatase) or the inhibition of CyP450.....or both?

Both, but in all likelihood, you need huge quantities to impact this desmolase system to any large degree.




Interesting thoughts, that do minimally display steroidogenesis is not as neat and clean as many supplement companies like to portray perhaps. Still steroids derived from Cholesterol (27 carbons) come in different fashions
(1) 80% from LDL
(2) 20% from HDL & Acetate (de novo synthesis)

Good info, cannot say that I've seen it broke down like that before.

Subsequently, cholesterol to Pregnenolone (21 carbons) is what is known as the rate limiting step with
(1) Cytochrome P450 Side Chain Cleavage enzyme (desmolase) which you mentioned, but also
(2) Controlled by ACTH, LH, FSH, etc., which are down in immediate post-cycle realms - especially gonadotropins without the use of something like Clomid and/or hCG
(3) This process only occurs in mitochondria

When you say rate limiting step doesnt that also make it the most important step in this process (steroidogenesis)? Also this would make sense as to the reason you would want to increase any of these variables:

1. LH
2. cAMP ------> protein kinase A (PKA)
3. StAR protein

What happens beyond the chol-->preg conversion is divergence of pathways
(1) Glucocorticoids
i. Cortisol
ii. Corticosterone
(2) Mineralocorticoids
i. Aldosterone
(3) Sex Steroids
1. Progestins
(a) pregnenelone
2. Progesterone (w/ interconversion amongst them all)
(a) Androgens
1. Testosterone
2. Androstendione
(b) Estrogens
1. Estradiol
2. Estrone
3. Estriol

The problem is you do not merely have adrenal sourcing alone in solitude. Here's where the imperative level of dosing, serum steady states and HPAA and HPTA crossover mechanisms all interplay. It gets quite complex.

Yeah I tend to get tunnel vision on these things. I guess it makes it easier for me to understand the smaller pieces first before putting it into the big picture.

I do think you'd have to ingest huge tallies of this stuff to have any level of impact to be honest with you and over long periods of time. Personally, as my initial post suggested in that other thread, it is likely to be relatively inconsequential in the grand scheme.


D_

Good info.

[Right Hook]

Originally Posted by dinoiii

Keep in mind, each of these adrenal cascades have pertinence in PCT. Mineralocorticoids, Glucocorticoids and Sex Steroids all interplay for a successful PCT in regards to body comp. Only incomplete PCT regimes don't consider that fact.

D_

I have to ask but is the adrenal really all that important when it accounts for such a small percentage of steroidogenesis? I realize it should not be completely written off but doesnt seem like it should be a focus.

Summary of Relative Contributions (appx. %) of major steroid origins

Testosterone
Testicular Secretion: ~ 95%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 4%

Dihydrotestosterone
Testicular Secretion: ~ 20%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 79%

Estradiol
Testicular Secretion: ~ 20%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 79%

Estrone
Testicular Secretion: ~ 2%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 97%

DHEA-S
Testicular Secretion: ~ 10%
Adrenal Secretion: ~ 90%
Peripheral Conversion of Precursors: Not usually detected

[dinoiii]

Originally Posted by Right Hook

I have to ask but is the adrenal really all that important when it accounts for such a small percentage of steroidogenesis? I realize it should not be completely written off but doesnt seem like it should be a focus.

Interesting notion, but the adrenal gland is what will work as your relative knight in shining armour while your testicular axes are wading their way out of disarray (i.e. - potential hypogonadism) in PCT.

Think of it in a time-dependent manner:

Post PCT:

Week 1: Both HPTA and HPAA shutdown
Week 2: Both HPTA and HPAA shutdown
Week 3: HPTA shutdown / HPAA upregulation
Week 4: HPTA shutdown / HPAA upregulation

The quicker you can regain control of the HPAA, the higher likelihood you will be able to regain control of testicular axes. Of course, I am not a fan of testicular axes per se (i.e. - HPTA) because that too can mean "thyroidal" axes, so I further breakdown into HPLCA and HPSTA for those who are avid readers of the PCT: ACV series.


D_

[dinoiii]

Originally Posted by Right Hook

Good info, cannot say that I've seen it broke down like that before.

This is actually one of the reason that I laugh when people suggest things like RYR have a place. Cholesterol is NOT the bad guy its made out to be, IF we are not talking about atherogenic dyslipidemia of course - but far too many "expert" authors have no idea what the hell I am talking about when I reference that, so I merely digress...

When you say rate limiting step doesnt that also make it the most important step in this process (steroidogenesis)? Also this would make sense as to the reason you would want to increase any of these variables:

1. LH
2. cAMP ------> protein kinase A (PKA)
3. StAR protein

I suppose that is a way to look at it. "Rate limitation" would dictate that everything downstream is subject to how fast (relative to respective substrate) that particular conversion in question occurs.

Again, this will dictate your success into PCT and how quickly you regain control of the essential endocrinologic disarray.



D_