Gonadin - Liquid Steroid Optimizer For Lab/R&D

[chispas]

Is Gonadin a supplement that could be taken alongside K2?

 

[Wagner83]

One of the more interesting studies I stumbled upon (which has been posted on the forum) demonstrated that administration of vitamin K2 (MK-4) to old rats doubled their testosterone levels without any addition of other stimulating agents like thyroid hormone, or NAD, or even precursors like pregnenolone. More importantly, Vitamin K2 did not affect pituitary hormones like LH, which are typically involved in steroidogenesis.

That vitamin K2 study apparently got the authors thinking what could be the reason behind this effect of boosting testosterone synthesis. Given that the quinone structure is the same in both K1 and K2, the only difference is the side chain. Vitamin K2 contains geranylgeraniol (GGOH) as a side chain, while vitamin K1 does not. So, the same authors decided to do another study using just GGOH as well as a few other related substances and examine their effects on steroidogenesis.
http://www.tandfonline.com/doi/abs/10.1080/09168451.2015.1123612?src=recsys&journalCode=tbbb20

As expected, GGOH did boost testosterone levels and in a concentration about the same as the one used in the first study with MK-4 - i.e. 10μM/L - 30μM/L. It also increased the synthesis of progesterone, which is an important direct precursor to steroid synthesis in the gonads, including synthesis of T. So, the testosterone-boosting effects of vitamin K2 (MK-4) appear to be due mostly to that side chain and not the quinone structure, which matches the results from the first study. Moreover, another similar terpene known as Phytol (POH) was even more effective than GGOH in boosting synthesis of both testosterone and progesterone in Leydig cells when used in concentrations of 30μM/L (see attached screenshots).
Phytol - Wikipedia
Phytol is quite an interesting substances as it is a precursor to both vitamin E and K and is used as raw material by some organisms who can synthesize these vitamins endogenously. More importantly, both of these vitamins have been found to raise T levels in animal (and some human) studies, which seems to be due to the presence of that side chain (derived from phytol) attached to the quinone ring. In addition, it was also discovered that phytol is a potent aromatase inhibitor with an IC50 of just 1μM/L, which is quite easily achievable with the amounts present is our product. In fact, in this study phytol (code-named SA-20 in the study and attached screenshots) was as effective as formestane (abbreviated FOR in the study and attached screenshots) in inhibiting estradiol synthesis when used in concentration of 1μM/L (see attached image). Formestane is a steroidal aromatase inhibitor similar to but more potent than exemestane. Perhaps even more importantly, phytol reduced mRNA expression of aromatase itself for up to 24 hours, which suggests that it acts as a long lasting "suicide aromatase inhibitor" just like formestane. In concentrations of 10μM/L, phytol was again as effective as formestane in decreasing actual aromatase expression. As mentioned above, the 100mg dose of phytol per serving (8 drops) of Gonadin should achieve 30μM/L concentrations, so the methods of the study on aromatase should be quite easily replicated. Overall, the aromatase inhibition effects of phytol could very well be responsible at least partly for the observed increase in testosterone levels, in addition to the stimulation of StAR. I am not aware of any other substance that can both inhibit aromatase (and long-lasting at that) AND promote endogenous testosterone/progesterone synthesis.

Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa ... - PubMed - NCBI
"Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). The effects of these two compounds on extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were examined."
"...It is found abundantly in nature as part of the chlorophyll molecule, and a relatively high amount of free phytol is present in dairy products (Brown et al., 1993). The finding in this study that phytol is a potent aromatase inhibitor gives new insight on our understanding of the beneficial effects of vegetables and fruit on human health."
"


The higher the levels of this protein, the more steroids are synthesize from cholesterol and (maybe even more importantly) from other precursors as well. Cholesterol is not the only precursor to steroid synthesis and we are just beginning to understand the role of these other precursors. But as far as the levels of StAR, GGOH (and POH) increased those level more than 6-fold. I am not aware of any other substance with such dramatic effects on upregulating StAR. Finally, contrary to what other studies have suggested and what some forum members have asked for, PDE levels did not correlate with steroid synthesis. So, a PDE inhibitor will probably not be as effective as a steroid booster compared to GGOH or POH.



Squalene is also known to protect from lipophilic xenobiotics like BPA and other aromatic hydrocarbons produced by modern industries, protect from radiation toxicity, reduce cholesterol levels, improve skin health, protect from certain cancers, reduce lipid and muscular lipid accumulation, prevent CVD, and others.

So some of the research in this post is geared towards vitamin K2 / GGOH, you say that phytol can be used by certain organisms to produce vitamin K and E (red), what makes you think humans will convert phytol into vitamin K2 (and Mk4 specifically) or vitamin E so that phytol will lead to their benefits as well?
Apart from its properties to inhibit aromatase (and correct me if I'm wrong but vitamin K2 also inhibit aromatase but boost StAR protein / testosterone level more), what are the advantages and differences between phytol and vitK2? I think estrogens levels can be quite well controlled by vitamin E, well cooked WBM away from meals (I actually get the same symptoms as too much androsterone after consuming lots of them), aspirin and a proper diet among other things.

Do you care to explain the blue part as I'm not sure what it means regarding cAMP ?

As for the purple quote I found the study here (Diet and Refsum's disease - Research Database - University of Hertfordshire) , and there's also this quote " Although humans cannot derive phytanic acid from chlorophyll, they can convert free phytol into phytanic acid. Thus, patients with Refsum disease should limit their intake of phytanic acid and free phytol.[5] The amount of free phytol in numerous food products has been reported.[6] "
Doesn't it suggest opposite effects to niacinamide as per the other study posted on a much discussed thread ?

 

[haidut]

Thanks!

Divided dose, or is the half life such that 1x day is all that is necessary?

One single dose is what I use.

 

[haidut]

Is Gonadin a supplement that could be taken alongside K2?

You can, but I don't know how much K2 will boost the effects.

 

[haidut]

So some of the research in this post is be geared towards vitamin K2 / GGOH, you say that phytol can be used by certain organisms to produce vitamin K and E (red), what makes you think humans will convert phytol into vitamin K2 (and Mk4 specifically) or vitamin E so that phytol will lead to their benefits as well?
Apart from its properties to inhibit aromatase (and correct me if I'm wrong but vitamin K2 also inhibit aromatase but boost StAR protein / testosterone level more), what are the advantages and differences between phytol and vitK2? I think estrogens levels can be quite well controlled by vitamin E, well cooked WBM away from meals (I actually get the same symptoms as too much androsterone after consuming lots of them), aspirin and a proper diet among other things.

Do you care to explain the blue part as I'm not sure what it means regarding cAMP ?

As for the purple quote I found the study here (Diet and Refsum's disease - Research Database - University of Hertfordshire) , and there's also this quote " Although humans cannot derive phytanic acid from chlorophyll, they can convert free phytol into phytanic acid. Thus, patients with Refsum disease should limit their intake of phytanic acid and free phytol.[5] The amount of free phytol in numerous food products has been reported.[6] "
Doesn't it suggest opposite effects to niacinamide as per the other study posted on a much discussed thread ?

Some of that information is in the original post. The very reason the authors of the vitamin K2 study decided to do that second study was because they suspected that the quinone portion of the vitamin K2 molecule is NOT responsible for the T boosting effects but it is the side chain (GGOH). It's even included as one of the quotes in that thread. So, the study is actually about side chains like GGOH, phytol, and farnesol being capable of boosting T. Phytol just happened to be the most potent at concentration of 30uM/L. The second study on aromatase inhibition also suggests that it is again the side chains like GGOH, POH, etc responsible for the aromatase inhibition properties of vitamin K2. I have seen other studies with pure quinones like emodin and 1,4-napthoquinone and they do not inhibit aromatase. Now, the quinone portion is probably very important for the pro-metabolic and anti-cancer effects of vitamin K2, but its hormone effects seem to be due to that side chain. Obviously, I would like to see more studies solidify this hypothesis but for now it is not a bad start.
What study suggested actions of niacinamide opposite to that of phytanic acid?

 

[Wagner83]

It's possible, but only if it inhibits baseline aromatase expression. If it inhibits mostly the abnormal increase due to cortisol and inflammation then it should not lead to rebounds upon stopping.

It would be nice to find more information on that but not sure that will be possible except for the feedback from the forums.

Some of that information is in the original post. The very reason the authors of the vitamin K2 study decided to do that second study was because they suspected that the quinone portion of the vitamin K2 molecule is NOT responsible for the T boosting effects but it is the side chain (GGOH). It's even included as one of the quotes in that thread. So, the study is actually about side chains like GGOH, phytol, and farnesol being capable of boosting T. Phytol just happened to be the most potent at concentration of 30uM/L. The second study on aromatase inhibition also suggests that it is again the side chains like GGOH, POH, etc responsible for the aromatase inhibition properties of vitamin K2. I have seen other studies with pure quinones like emodin and 1,4-napthoquinone and they do not inhibit aromatase. Now, the quinone portion is probably very important for the pro-metabolic and anti-cancer effects of vitamin K2, but its hormone effects seem to be due to that side chain. Obviously, I would like to see more studies solidify this hypothesis but for now it is not a bad start.
What study suggested actions of niacinamide opposite to that of phytanic acid?

What I mean is that some of the research you put forward is done on vitamin K2 and GGOH, not phytol . As you said with vitamin K2 you get the pro metabolic anti cancer effects as well as a boost in testosterone and possibly some anti aromatase effects . The obvious advantage of K2 is that there have been human trials and afaik toxicity is very hard to achieve (if even possible). Phytol worked a little bit better than GGOH (and therefore the 1-4 mg K2 on scrotum is that right?) but looking at the image you attached they were very close, as I recall vit K 2 / GGOH also multiplied the levels of StAR by 6 (in vitro though).
From what I've read it seems we , unlike any other species, can't extract phytol from food so I wonder how good can it be?
The potent anti aromatase effects on certain cells is interesting though, especially if it's more of a regulator of abnormal anti aromatase activity .

The one that was well discussed and showed fat accumulation in muscles (opposite to what squalene did): NIACINAMIDE DECREASES Liver And Muscle GLYCOGEN .

If you have the time I would appreciate if you could explain this:

""Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB)"

Doesn't it suggest that it interferes with the cAMP/PKA pathway? Sorry, my knowledge is limited..

 

[haidut]

It would be nice to find more information on that but not sure that will be possible except for the feedback from the forums.



What I mean is that some of the research you put forward is done on vitamin K2 and GGOH, not phytol . As you said with vitamin K2 you get the pro metabolic anti cancer effects as well as a boost in testosterone and possibly some anti aromatase effects . The obvious advantage of K2 is that there have been human trials and afaik toxicity is very hard to achieve (if even possible). Phytol worked a little bit better than GGOH (and therefore the 1-4 mg K2 on scrotum is that right?) but looking at the image you attached they were very close, as I recall vit K 2 / GGOH also multiplied the levels of StAR by 6 (in vitro though).
From what I've read it seems we , unlike any other species, can't extract phytol from food so I wonder how good can it be?
The potent anti aromatase effects on certain cells is interesting though, especially if it's more of a regulator of abnormal anti aromatase activity .

The one that was well discussed and showed fat accumulation in muscles (opposite to what squalene did): NIACINAMIDE DECREASES Liver And Muscle GLYCOGEN .

If you have the time I would appreciate if you could explain this:
Doesn't it suggest that it interferes with the cAMP/PKA pathway? Sorry, my knowledge is limited..

Apparently, humans obtain 50mg - 100mg phytanic acid from food daily.
Phytanic acid - Wikipedia
"...Phytanic acid (or 3,7,11,15-tetramethyl hexadecanoic acid) is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish.[1] Western diets are estimated to provide 50–100 mg of phytanic acid per day.[2] In a study conducted in Oxford, individuals who consumed meat had, on average, a 6.7-fold higher geometric mean plasma phytanic acid concentration than did vegans."

Given that it is the phytanic acid that caused the issues in Refsum disease and other fat-accumulation pathologies, I doubt that the precursor phytol in basically physiological amounts would cause much harm. But of course, more studies are needed to say with more certainty. Both the squalene and phytol are present in Gonadin in amounts that are achievable with food, albeit with some effort. But I would certainly not gobble it up like candy, as I mentioned it another post.
And yes, that post suggests it is inhibiting the cAMP/PKA pathway, which seems to be the opposite to what the study on GGOH and POH found. Not sure what to make of it, but the cell culture used in the aromatase study was different and maybe the effects are different as well.

 

[Wagner83]

Apparently, humans obtain 50mg - 100mg phytanic acid from food daily.
Phytanic acid - Wikipedia
"...Phytanic acid (or 3,7,11,15-tetramethyl hexadecanoic acid) is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish.[1] Western diets are estimated to provide 50–100 mg of phytanic acid per day.[2] In a study conducted in Oxford, individuals who consumed meat had, on average, a 6.7-fold higher geometric mean plasma phytanic acid concentration than did vegans."

Given that it is the phytanic acid that caused the issues in Refsum disease and other fat-accumulation pathologies, I doubt that the precursor phytol in basically physiological amounts would cause much harm. But of course, more studies are needed to say with more certainty. Both the squalene and phytol are present in Gonadin in amounts that are achievable with food, albeit with some effort. But I would certainly not gobble it up like candy, as I mentioned it another post.
And yes, that post suggests it is inhibiting the cAMP/PKA pathway, which seems to be the opposite to what the study on GGOH and POH found. Not sure what to make of it, but the cell culture used in the aromatase study was different and maybe the effects are different as well.

Well as for the phytol I don't know, unless you consider we turn all the phytol into phytinic acid and therefore 50-100 mg of phytinic acid = 50-100mg phytol. Otherwise ruminants and some other species seem to extract the phytol from plants (chlorophyll) , our intake is close to non existent from what I can see but I have not investigated the matter like a madman (to say the least).
As for squalene in food, this paper suggests shark liver oil is half to 80% squalene , and olive oil can have from 1mg to as much as 6mg / g! Besides olive oil (sounds possible to reach 100 mg with it) there ain't many relevant sources of squalene I can think of.

 

[haidut]

Well as for the phytol I don't know, unless you consider we turn all the phytol into phytinic acid and therefore 50-100 mg of phytinic acid = 50-100mg phytol. Otherwise ruminants and some other species seem to extract the phytol from plants (chlorophyll) , our intake is close to non existent from what I can see but I have not investigated the matter like a madman (to say the least).
As for squalene in food, this paper suggests shark liver oil is half to 80% squalene , and olive oil can have from 1mg to as much as 6mg / g! Besides olive oil (sounds possible to reach 100 mg with it) there ain't many relevant sources of squalene I can think of.

Phytol itself is actually present in milk in decent amounts. As the quote from the main thread says. So, we do get it fro food. And here is another one on phytol contents in milk
Characterization of two steroidal ketones and two isoprenoid alcohols in dairy products. - PubMed - NCBI

Squalene is present in many plants, including olives and olive oil. If you eat a decent amount of olive oil (20g+) daily then you are getting 100mg+ squalene.

 

[miki14]

Effects of squalene/squalane on dopamine levels, antioxidant enzyme activity, and fatty acid composition in the striatum of Parkinson's disease mou... - PubMed - NCBI

The squalene in Gonadin is mostly as a booster. The primary ingredient is Phytol as that is what increased StAR activity 6-fold and T/progesterone levels several fold. The squalene in commercially sold EVOO was tested a few times and it was found to be very low.

I always loved whole olives and found them to have a strong anti-stress effect. I wonder if this is due to the squalene content?

 

[Wagner83]

Phytol itself is actually present in milk in decent amounts. As the quote from the main thread says. So, we do get it fro food. And here is another one on phytol contents in milk
Characterization of two steroidal ketones and two isoprenoid alcohols in dairy products. - PubMed - NCBI

Ok do you have any idea in what amount it is present in milk and dairy products? I could not find anything.

Also from the original post I read: " We showed that GGOH treatment increased the RNA and protein levels of StAR, which acts downstream in the cAMP/PKA pathway." I do not see them mention phytol but haven't found the link to the study. Also if phytol interferes with the cAMP/PKA pathway and StAR acts downstream of that it sounds counterproductive. I wonder if vit K2 + coffee on scrotum (not coffee on scrotum...) would still be effective if phytol is taken orally.

 

[haidut]

Ok do you have any idea in what amount it is present in milk and dairy products? I could not find anything.

Also from the original post I read: " We showed that GGOH treatment increased the RNA and protein levels of StAR, which acts downstream in the cAMP/PKA pathway." I do not see them mention phytol but haven't found the link to the study. Also if phytol interferes with the cAMP/PKA pathway and StAR acts downstream of that it sounds counterproductive. I wonder if vit K2 + coffee on scrotum (not coffee on scrotum...) would still be effective if phytol is taken orally.

That same study used phytol, farnesol and a GGPP as comparison to GGOH. The effectiveness of phytol was through the same mechanism. I think I extracted the quotes mentioning phytol. I think vitamin K2 would not hurt to add on top of Gonadim, especially when used on the scrotum. The higher concentration tested in the original vitamin K2 study was 100uM, so there is quite a bit of room from 30uM to 100uM to add extra vitamin K2 and potentially get even stronger effects.
I will look through some food databases to see how much phytol is in dairy, and post here.

 

[Wagner83]

That same study used phytol, farnesol and a GGPP as comparison to GGOH. The effectiveness of phytol was through the same mechanism. I think I extracted the quotes mentioning phytol. I think vitamin K2 would not hurt to add on top of Gonadim, especially when used on the scrotum. The higher concentration tested in the original vitamin K2 study was 100uM, so there is quite a bit of room from 30uM to 100uM to add extra vitamin K2 and potentially get even stronger effects.

I will look through some food databases to see how much phytol is in dairy, and post here.

I asked since vitamin K2 and coffee seem to work in a different/contradictory way to phytol:
Raising Serum Androgens Using DHEA, Pregnenolone, And Vitamin K

"This means, if you are using vitamin K2 (and DHEA/pregnenolone) without any cAMP stimulation then using a dose of 3mg - 5mg is needed. The dose in milligrams for vitamin K2 (MK-4) is higher than DHEA since the molar mass of MK-4 is much higher than the one for DHEA. So, consequently more mass is needed to achieve the same molar concentration. However, if you are using caffeine on a regular basis, which potently raises cAMP, then the optimal dose of vitamin K2 (MK-4) would be about 1mg per serving, as in the presence of increased cAMP using 30μM of vitamin K2 (MK-4) worked better than 100μM."

and

"Phosphorylation levels of the catalytic subunit of PKA (p-PKA) in I-10 cells were significantly increased by MK-4 treatment at the 2 h and 3 h time points (Figures (Figures7A7A and and7B),7B), while total PKA levels were not changed (data not shown). In addition, phosphorylation levels of CREB (p-CREB), a typical substrate of PKA, were significantly increased by treatment with MK-4 after 3 h (Figure (Figure7B).7B). Both p-PKA and p-CREB levels were higher in I-10 cells at 9 h post-treatment (data not shown). Conversely, enhanced testosterone production induced by MK-4 was abolished by treatment with H89, a specific inhibitor of PKA (Figure (Figure8).8). Together, these results indicate that MK-4 increases testosterone production in I-10 cells by upregulating CYP11A expression through the activation of PKA.""

Versus

"
Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa ... - PubMed - NCBI
"Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). "

So I'm not sure if one is better than an other but it sounds like they wouldn't work too well together, unless one can somehow keep the concentration of phytol at the appropriate level in the tissues and keep the testicles free while MK4 reaches its optimal concentration (with coffee 30μM apparently is better than 100) in the latter two (or latter one for the unlucky). Just a wild guess from a forum member .

Ok thanks.

 

[Constatine]

We'll one study was looking at I-10 cells and the other human ovarian granulosa-like KGN cells. I don't know if the results are comparable.
One of the studies suggested that GGOH worked via upregulating PKA in I-10 cells. Same as mk-4 obviously but how do we know phytol works through the same mechanism (I can't read the full study).

 

[haidut]

I asked since vitamin K2 and coffee seem to work in a different/contradictory way to phytol:
Raising Serum Androgens Using DHEA, Pregnenolone, And Vitamin K


and


Versus



So I'm not sure if one is better than an other but it sounds like they wouldn't work too well together, unless one can somehow keep the concentration of phytol at the appropriate level in the tissues and keep the testicles free while MK4 reaches its optimal concentration (with coffee 30μM apparently is better than 100) in the latter two (or latter one for the unlucky). Just a wild guess from a forum member .

Ok thanks.

Where did you see that vitamin K2 works in a contradictory way to phytol and/or GGOH? Different - maybe, but contradictory - I do not see that implied anywhere. Again, the very reason the study with GGOH and phytol was done was to understand how vitamin K2 increases T synthesis. The conclusions of that study, mostly focusing on GGOH, was this:
"...These isoprenoids - including FOH, GOH and POH - regulate various biological processes [20-22]. The results of this study indicate that not only GGOH, but other isoprenoid derivatives can enhance testosterone and progesterone levels, although the mechanism by which other isoprenoids exert these effects has yet to be determined."

So, I already emailed the authors and asked about both plausible pathways for phytol and also opinion on safety. Let's see what they come back with. As far as phytol contents in food, this study shows that a typical Western diet provides 50mg - 100mg phytanic acid per day.
Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions | BMC Physiology | Full Text
"...The phytanic acid content of Western diets (50-100 mg daily intake) [43] is estimated to be at least 10 × greater than its free phytol content [41, 60]. Since phytanic acid is primarily found in ruminant fats (organic beef fat has >325 mg/100 g), dairy products (45% fat cream cheese has >125 mg/100 g), and fish (canned salmon has >250 mg/100 g) [41], human vegans are appropriate for our studies."

Given that it is phytanic acid that can pose problems for people with Refsum disease and less than 10% of ingested phytol is converted to phytanic acid, the 100mg phytol from a daily dose of Gonadin falls quite within the physiological range of what a person might eat. And if a person eats a lot of ruminant and dairy products the daily ingested amount of phytanic acid may be even higher. Btw, phytol is also present in olive oil but the data on contents is very sparse.
Bottom lime is this - the amounts present in Gonadin of both squalene and phytol fall within the dose range typically ingested from a Western diet. Gonadin also contains vitamin E to protect from possible peroxidation effects of these two unsaturated substances. As I mentioned a few times before, using the recommended dose of 8 drops should keep everything within the physiological range and should not be more dangerous than your typical daily diet.

 

[thyrulian]

Suppressing CREB phosphorylation
(in general) seems the way to go.
Estrogen & BPA especially enhance phospho-CREB, I think through calcium influx, promoting dynorphin's hold on dopaminergic signaling.
It is a major characteristic of the stressed/addicted state.

 

[haidut]

Suppressing CREB phosphorylation
(in general) seems the way to go.
Estrogen & BPA especially enhance phospho-CREB, I think through calcium influx, promoting dynorphin's hold on dopaminergic signaling.
It is a major characteristic of the stressed/addicted state.

Thanks, good to know.

 

[PUTFOT]

Any other effects you noticed this far @haidut ?

 

[Constatine]

Suppressing CREB phosphorylation
(in general) seems the way to go.
Estrogen & BPA especially enhance phospho-CREB, I think through calcium influx, promoting dynorphin's hold on dopaminergic signaling.
It is a major characteristic of the stressed/addicted state.

I supose this means phytol has anti-addiction properties. And that plastic has addiction promoting properties. It does concern me that mk-4 was found to increase CREB phosphorylation. Perhaps this is why some people experience a worse mood on mk-4. Still dynorphin does have vastly different effects depending on where it's located. But I've never heard of any of these effects being very positive. Maybe this effect exsists to make people seek foods high in vitamin k.

 

[Wagner83]

Where did you see that vitamin K2 works in a contradictory way to phytol and/or GGOH?

So, I already emailed the authors and asked about both plausible pathways for phytol and also opinion on safety. Let's see what they come back with.

Given that it is phytanic acid that can pose problems for people with Refsum disease and less than 10% of ingested phytol is converted to phytanic acid, the 100mg phytol from a daily dose of Gonadin falls quite within the physiological range of what a person might eat. And if a person eats a lot of ruminant and dairy products the daily ingested amount of phytanic acid may be even higher. Btw, phytol is also present in olive oil but the data on contents is very sparse.

As Contantine and these quotes said:

Vitamin K2 Mk4 / GGOH:

"Phosphorylation levels of the catalytic subunit of PKA (p-PKA) in I-10 cells were significantly increased by MK-4 treatment at the 2 h and 3 h time points (Figures (Figures7A7A and and7B),7B), while total PKA levels were not changed (data not shown). In addition, phosphorylation levels of CREB (p-CREB), a typical substrate of PKA, were significantly increased by treatment with MK-4 after 3 h (Figure (Figure7B).7B). Both p-PKA and p-CREB levels were higher in I-10 cells at 9 h post-treatment (data not shown). Conversely, enhanced testosterone production induced by MK-4 was abolished by treatment with H89, a specific inhibitor of PKA (Figure (Figure8).8). Together, these results indicate that MK-4 increases testosterone production in I-10 cells by upregulating CYP11A expression through the activation of PKA.""

Phytol:
Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa ... - PubMed - NCBI
"Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). "

--------------------------------
Nice I look forward to their answer. If you can ask them about the potential aromatase rebound effect mentioned earlier it would be great.

Olive oil has quite a few interesting properties then.

Suppressing CREB phosphorylation
(in general) seems the way to go.
Estrogen & BPA especially enhance phospho-CREB, I think through calcium influx, promoting dynorphin's hold on dopaminergic signaling.
It is a major characteristic of the stressed/addicted state.

Thanks I found those links on the matter:
Involvement of cyclic AMP response element binding protein (CREB) and estrogen receptor phosphorylation in the synergistic activation of the estrog... - PubMed - NCBI
Multisite phosphorylation of the cAMP response element-binding protein (CREB) by a diversity of protein kinases. - PubMed - NCBI
Our Stolen Future:Transcription factor CREB activated by low level Bisphenol A.
Low doses of the endocrine disruptor bisphenol-A and the native hormone 17beta-estradiol rapidly activate transcription factor CREB. - PubMed - NCBI

More on BPA:
Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor wit... - PubMed - NCBI