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Old 12-12-2004, 08:54 PM   #1
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DGAT1 Inhibitors for Acne treatment

DGAT1 inhibition decreases or eliminates acne. The fact is being researched right now in industry according to someone in the know.

red sage is the most potent DGAT1 inhibitor, but it is usually not standardized for the inhibiting substance in it.

Has anyone researched the fact?

I have taken DGAT1 inhibitors and they work. Just looking for a cheaper route.

 
Old 12-29-2004, 10:01 PM   #2
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Re: DGAT1 Inhibitors for Acne treatment

I also propose that the reason that Niacin works (marginally) is due to the fact that it has recently been discovered to be a DGAT2 inhibitor:

------------------

Niacin is a widely used lipid-regulating agent in dyslipidemic patients. Previously, we have shown that niacin inhibits triacylglycerol synthesis. In this report, using HepG2 cells, we have examined the effect of niacin on the mRNA expression and microsomal activity of diacylglycerol acyltransferase 1 and 2 (DGAT1 and DGAT2), the last committed but distinctly different enzymes for triglyceride synthesis. Addition of niacin to the DGAT assay reaction mixture dose-dependently (0–3 mM) inhibited DGAT activity by 35–50%, and the IC50 was found to be 0.1 mM. Enzyme kinetic studies showed apparent Km values of 8.3 µM and 100 µM using [14C]oleoyl-CoA and sn-1,2-dioleoylglycerol as substrates, respectively. A decrease in apparent Vmax was observed with niacin, whereas the apparent Km remained constant. A Lineweaver-Burk plot of DGAT inhibition by niacin showed a noncompetitive type of inhibition. Niacin selectively inhibited DGAT2 but not DGAT1 activity. Niacin inhibited overt DGAT activity. Niacin had no effect on the expression of DGAT1 and DGAT2 mRNA.

These data suggest that niacin directly and noncompetitively inhibits DGAT2 but not DGAT1, resulting in decreased triglyceride synthesis and hepatic atherogenic lipoprotein secretion, thus indicating a major target site for its mechanism of action.

--------------------

Keep your eyes open. This is going to be the solution to acne in the near future..

 
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Old 12-29-2004, 10:37 PM   #3
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Re: DGAT1 Inhibitors for Acne treatment

Ahh, so then I should suggest that more people take Nicomide then?

Nicomide is a new oral prescription for acne that's appears to have been out at least 1 or 2 years now that contains a very high dose of a form of Niacin (750mg), along with Zinc (25mg), Folic Acid (500mcg), and Copper (1.5mg) by Sirius. The manufacturer says that it's anti-inflammatory properties are comparable to antibiotics.

I don't know about DGAT2 inhibition, but I have run across various factors involved with lipid production and prostaglandin production that end in inflammation. These factors seem to be high in acne sufferers, among other people with health problems (such as Metabolic Syndrome/Insulin Resistance Syndrome). For example, one of these factors among twins with acne was a deficiency of Apoliprotein A1 (a part of HDL cholesterol). So when I'm not so tired I'll definately check into DGAT2.

Thanks =)

 
Old 12-29-2004, 11:18 PM   #4
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Re: DGAT1 Inhibitors for Acne treatment

It may be oversimplistic of me, but the common ground here is blood TAG levels and fat storage signaling. The lemon juice thread caught my attention because citric acid may increase Malonyl-CoA which causes (i think) higher FFA/TAG ratio. This ratio is very very important in research right now (for diabetes, obesity, etc.).

Also, I think that DGAT inhibition has effects on sebum production, not inflammation. Not sure though.

Last edited by Paracelsus; 12-29-2004 at 11:19 PM.

 
Old 12-29-2004, 11:34 PM   #5
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Re: DGAT1 Inhibitors for Acne treatment

No I don't think it's oversimplistic. Our bodies produce the steriod hormones neccessary for acne from fats, more specifically cholesterol. Fats, fatty acids, are also responsible for production of pro-inflammatory products. I guess the question is which is more important.

If you go the route that you are headed, I would say it's the reduction of inflammatory products as sebum production (high or low amounts) doesn't appear to be neccessary for acne formation. Yet it could be what's IN the sebum that may be of concern, particularly when we are looking at those that produce lots of sebum that have severe acne. Again inflammatory products comes to mind. Have you run into anything dealing with pro-inflammatory cytokines (Interleukin 1 or 6) or the "bad" prostaglandin (PGE2), or inflammatory arachidonic acid (fatty acid) along with DGAT2?

Also did you investigate NACs (n-acetyl cysteine) role in this and did you ever make your ECGC patch?

Last edited by SweetJade1; 12-29-2004 at 11:47 PM.

 
Old 12-30-2004, 02:41 AM   #6
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Re: DGAT1 Inhibitors for Acne treatment

Wow, I understood almost none of what you two just said, but I'm going to start researching all of it. I think you two need to keep corresponding and let us know what you guys discover.

With any luck, after enough research, I'll be able to add some kind of valuable insight.
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Old 12-30-2004, 04:03 PM   #7
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Re: DGAT1 Inhibitors for Acne treatment

Great guys this does sound very interesting. I have read that Chinese Medicine actively promotes the use of Red Sage in dealing with skin conditions especially with females that have hormonal problems. I'm not very clued up on the science behind it i.e. that it is a DGAT1 inhibitor but I'm definitely willing to give it a try if Paracelsus you say it worked for you Did you stop taking Red Sage because it is expensive? Is it safe for males to take this herb because if it affects the hormones in any way I really don't wanna risk ending up becoming a female lol?

If Niacin in high doses works well why can't you combine the two to increase the chances of efficacy?

Thanks for the info guys and keep up the good work

 
Old 12-30-2004, 06:54 PM   #8
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Re: DGAT1 Inhibitors for Acne treatment

Well I have to admit that the expert in DGAT1 inhibitors in salvia is not I. If you search on google you will find him - i think his handle comes up as the first 10 hits

and he is the one I will ask about niacin. I seriously doubt that it has been overlooked.

Also, red sage extract is usually standardized for tanshinone IIA and IIB which are the weakest of the DGAT inhibitors. The strongest DGAT inhibiting extracts are a trade secret. I'm workin on it though.

and no i never stopped taking it - i take it in a "proprietary blend" developed by Avant Labs for metabolic repartitioning... and all 3 ingredients in the blend also help skin. Its no suprise to me that metabolic alterations have a huge impact on acne (specifically, ones that target fatty acid trafficking, signaling, and storage).

As far as my research in DGAT2- i just accidentally came accrossed a new study so I was just poking around to see if this is new or old news. Perhaps the incorrect pathway has been previously postulated as to why niacin works (marginally) for acne.

As far as ECGC- well I hate to be a downer but I've come to the biased opinion that it is most likely the fatty acid synthase inhibition of ECG not the 5-ht inhibition of ECGC (5-ht? i forget which enzyme we're talking about) that has the more profound effect on acne. I could probably provide evidence if i could find extracts standardized for each.

 
Old 12-30-2004, 08:07 PM   #9
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Re: DGAT1 Inhibitors for Acne treatment

This is a bit confusing, but I came across a few articles discussing DGAT 1 and obesity, insulin sensitivity as well as sebaceous gland supression.

Basically the studies were done using mice, but a defeciency in DGAT 1 led to seemingly poor functioning sebaceous glands to the point where hair luster & loss even occured. Despite adding androgens (which should fuel sebum production), sebum production did not occur.

Anyway, take a look at these (full text) and tell me what you think as they mention this is aided by an INCREASE in DGAT 2 [url]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11805129[/url]

[url]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12401709[/url]

OK, LOL, I was reading wrong. This makes sense. The goal for this discussion is DGAT 1 inhibition (to a degree), but I was thinking you were talking about DGAT 2 Inhibition (darn niacin article)!

Last edited by SweetJade1; 12-30-2004 at 08:09 PM.

 
Old 12-30-2004, 08:25 PM   #10
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Re: DGAT1 Inhibitors for Acne treatment

yeah there are DGAT1 knockout mice and that is where all of the data comes from... and you are correct: there is a difficiency in sebocyte production when DGAT1 is inhibited...

DGAT1 receptors are located mainly in the liver and DGAT2 receptors mainly in hair and skin.

Impressive how quickly you found that article. Bravo!

btw the suppression of DGAT1 causes activation of DGAT2. Gets yah thinkin

Last edited by Paracelsus; 12-30-2004 at 08:27 PM.

 
Old 12-31-2004, 10:43 AM   #11
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Re: DGAT1 Inhibitors for Acne treatment

Paracelsus where do you get your "proprietary blend" developed by Avant Labs from as I am really interested in purchasing some and what are the remaining 3 'magic ingredients if you don't mind elaborating a little?

Do either of you guys know whether Red Sage is at all similar to the herbal Sage that is used for enhancing memory (or so they say) as I was told by a worker in a health food store that they are however I am sceptical? It was not in tablet/capsule form but rather the herbal form to make tea with.

Furthermore, is it definitely safe for guys to take? Thanks!!!

Quote:
Originally Posted by Paracelsus
The strongest DGAT inhibiting extracts are a trade secret. I'm workin on it though.
Lol are you planning on infiltrating the Red Sage Manufacturing Complex? Only joking but why are they a trade secret and how on earth are we supposed to know which one is the right 'Sage' to get them ? Hope you track it down.

 
Old 12-31-2004, 04:42 PM   #12
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Re: DGAT1 Inhibitors for Acne treatment

Quote:
Originally Posted by Neca
Paracelsus where do you get your "proprietary blend" developed by Avant Labs from as I am really interested in purchasing some and what are the remaining 3 'magic ingredients if you don't mind elaborating a little?

Do either of you guys know whether Red Sage is at all similar to the herbal Sage that is used for enhancing memory (or so they say) as I was told by a worker in a health food store that they are however I am sceptical? It was not in tablet/capsule form but rather the herbal form to make tea with.

Furthermore, is it definitely safe for guys to take? Thanks!!!



Lol are you planning on infiltrating the Red Sage Manufacturing Complex? Only joking but why are they a trade secret and how on earth are we supposed to know which one is the right 'Sage' to get them ? Hope you track it down.
I don't think i can post links but "Bulk Nutrition" has a deal with Avant Labs not to release any raw materials for another 2 months.

The other 2 ingredients in the product are sesamin and GPA. Sesamin is a ppar-alpha agonist and anti-inflammatory which has a mode of action similar to fibric acid--- and i made a post about that a while back. GPA is an AMPK agonist which should theoretically improve skin as well. As of right now it's all that i use for skin treatment. The only problem is that GPA is best when cycled on and off and when its "off", it's obvious.

 
Old 12-31-2004, 06:46 PM   #13
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Re: DGAT1 Inhibitors for Acne treatment

still thinking....

Last edited by SweetJade1; 12-31-2004 at 07:49 PM.

 
Old 01-01-2005, 01:40 AM   #14
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Re: DGAT1 Inhibitors for Acne treatment

Quote:
Originally Posted by Neca
Furthermore, is it definitely safe for guys to take? Thanks!!!

Lol are you planning on infiltrating the Red Sage Manufacturing Complex? Only joking but why are they a trade secret and how on earth are we supposed to know which one is the right 'Sage' to get them ? Hope you track it down.
Yes it's definitely safe for guys to take. Interestingly, ppar-alpha agonists such as strong fibrates will decrease libido in men. A SUPER high dose of the sesamin (a ppar-alpha agonist) could cause sexual side effects. I would guess that this only occurs in very few men and it's entirely reversible under cessation. I wouldn't worry about this though, becuase many people have taken 10x rec'd dose with no decrease in libido. Sesamin is a slight thermogenic. Red Sage has no sides aside from losing fat without trying

Someone has already infiltrated the Red Sage MFR complexes. I think he speaks chinese and he has a year or more of searching in this particular extract all over the world. The golden extract is the one that is not standardized for trashonone IIa and IIb, but another (or other stronger) trashonones. Free articles on this subject are scarce on the internet.

The Salvia plants are quite easy to grow, especially in my area. I would like to extract it myself as I am a biochemical engineer and i work as an organic chemist for the local university.. i think i could do it cheap

 
Old 01-01-2005, 06:22 PM   #15
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Re: DGAT1 Inhibitors for Acne treatment

OK wow well Paracelsus you have definitely got me very interested in this especially after doing some further research into Salvia Miltiorrhiza (Red Sage). It does seem very difficult to track down a good source of the correct version of SM i.e. the trashonones version as you mention above but Avant Labs have a product called Phenogen that contains the Salvia Miltiorrhiza, Sesamin and GPA so I assume this is the one you were referring to in your previous post.

I was browsing the Avant Labs' postings by other people and came across the Salvia post where someone was asking about whether AL could produce/release the 'special' Salvia ingredients but due to this so called 2-month agreement they can't. Well surely we can buy the extracts off them? Why don't they mass produce it for people fighting acne if it is so effective?

There are a few things that worry me about this product Phenogen however: firstly the fact that you said the Sesamin can lower your libido...well I really don't wanna do that if I have the choice and don't wanna risk damaging anything internally that could be permanent (if that is possible). Secondly that the product is used to lose weight but as I am at optimum weight losing any would not be neither my intention nor beneficial.

This is why I really do hope we can find a way to get the Salvia Miltiorrhiza extract from the company either via buying it or from another supplier as SM has NO side effects and it seems like it is potent at preventing acne . Surely all we need it to speak to a Chinese Herbal Practitioner?

Unfortuantely, as you say, there is very little info regarding this matter which doesn't help much but it is great that you are a biochemical engineer/organic chemist so I'm sure you know your stuff

I will keep checking those posts at AG to see if anything new pops up.

 
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