73 replies to this topic

[lucid]

I figured that most all things which we ingest can be dangerous if taken in too high of amounts I figured that it was possible to take too much. Perhaps I was incorrect and a u shaped curve doesn't describe the benefits. I know milk thistle can have a diarrhetic effect if too much is taken via increased bile production, but apparently the body will acclimatize to this and the diarrhetic symptoms should decline.

[bixbyte]

For all you miralax experimenters.
I found this $2 coupon for miralax, while supplies last:

http://www.miralax.com/default.html

click print coupon below (they let me print twice)

Alex

What is optimal dosing for silymarin? I am currently taking 250x2mg (500mg) of thistle milk (80% silymarin) in the morning. It appears that Silymarin has poor bioavailability and is almost impossible to OD on orally:

Something else which some of you might find interesting:

I don't know how one would go about including the β-cyclodextrin (a starch) with silymaring, but maybe someone does.

No 0ne knows the optimum dose; from the structural similarity of silybin, the most active component, to butein, a known SIRT1 activator that is half as potent by weight as resveratrol, one might make a stab at a first approximation that silybin is similarly active. I did the math near the beginning of this thread, and concluded that a capsule containing 170 mg of Silymarin is roughly equivalent to 50 mg of resveratrol. Based on self-administration of this compound and of synthetic and 98% resveratrol extracts, I believe this equivalence is reasonably accurate.

The inclusion of cyclodextrin and silymarin would be similar to the method Proteomist and I have described in another thread on resveratrol bioavailability, and in the 500 mg Resveratrol users thread (the thread that never ends.) The difference is the method calls for PEG 3350, which is readily available in any drug store, but this method should work for Cyclodextrine and Silymarin as well.

Let us say one desires to make a 500 mg dose of resveratrol (or silymarin, in this case.) One needs a good grade of extract with very small particl size, almost dusty. Mirronized would be best.

Weigh 600 mg of Miralax, and stir into 1/4 cup (4 oz, or about 120 milliliters) of water.
Stir until thoroughly dissolved.
Add 500 mg of resveratrol (or silymarin)
Stir thoroughly, until the resveratrol is suspended in the water, resulting in a milky-white lliquid.

The mixture will not settle, but remain in suspension indefinitely, except for any larger resveratrol particles that clump together without being bound by the Miralax. One may drink the liquid.

To make a PEG 3350 "inclusion", one would evaporate the liquid; the resulting powder will be a water soluble form of resveratrol.

This method should work with cyclodextrin as well as PGE3350, and with Silymarin in place of resveratrol. However, I've not actually tried it, and there may be some caveats. Silymarin is usually sold as an 80% extract. The other plant substances present may affect the process in some unpredictable way. I've not used cyclodextrin myself, though the description from those who have indicate the method should wrk, if the mixture is stirred vigorously. Cyclodextrin does not work as a detergent (one end charged,, one end neutral, so it can bond to both insoluble substances and to water.) Cyclodextrin molecules form a ring which traps other molecules, and acts as a carrier: it is water soluble, and so carries insoluble molecules along for the ride, so to speak.

I intend to try Miralax and silymarin within the next few days. I'll report back, if someone (Bixbyte? Lucid?) doesn't beat me to it.

[maxwatt]

I just tried your suggestion and mixed 750mg of Milk Thistle with peg 3350, and Blah, let me tell you, it tastes Horrible much worse than resv mixed with peg. It mixes in with PEG well, but I recommend you keep that milk thistle in its gel cap! Thanks for your advice about silymarin dosages maxwatt.

.....

Sorry about the flavor. Maybe lecithin would taste better?...?

I tried 80% silymarinn powder with Miralax for a Vitamin Shoppe capsule I opened. First observation: the particles were not suffieicntly fine as they were with the 98% resveratrol I import. Therefore the powder didn't go into suspension as well, most of it clumped together and stuck to the sides of the glass. The taste was like bitter grass clippings. Not a tasty treat, but nowhere near as horrible as your description

I may try lecithin as a surfactant. Reports from others suggest it is easier to mix up than Miralax, and it may help mask unpleasant flavors.

[edward]

Sorry to rain on the parade but there is a big concern for me with silymarin. It has been shown to be pro estrogen. Not only being estrogenic in and of itself but also to promote the action of endogenous estrogen. Here is a selected article though there are numerous ones just google estrogen estrogenic and silymarin or milk thistle.

Silymarin as a Estrogen agonist

I do take milk thistle but don't think that taking huge dosages would be very good for males. Resveratrol has been shown to be anti-estrogen which is another reason for men to want to use it.

Another Reference Showing Silymarin as a Pro-Estrogen Compound

[wydell]

When is someone going to come out with micronized resveratrol? Maybe Anthony will? What's involved in micronizing?

I assume that the technique below was learned from the Sirtris patent application. I have not read the application, but I wonder to what extent techniques derived from the application might read on the claims, should the patent be awarded.


[quote][quote]
Let us say one desires to make a 500 mg dose of resveratrol (or silymarin, in this case.) One needs a good grade of extract with very small particl size, almost dusty. Mirronized would be best.

Weigh 600 mg of Miralax, and stir into 1/4 cup (4 oz, or about 120 milliliters) of water.
Stir until thoroughly dissolved.
Add 500 mg of resveratrol (or silymarin)
Stir thoroughly, until the resveratrol is suspended in the water, resulting in a milky-white lliquid.

The mixture will not settle, but remain in suspension indefinitely, except for any larger resveratrol particles that clump together without being bound by the Miralax. One may drink the liquid.

To make a PEG 3350 "inclusion", one would evaporate the liquid; the resulting powder will be a water soluble form of resveratrol.

This method should work with cyclodextrin as well as PGE3350, and with Silymarin in place of resveratrol. However, I've not actually tried it, and there may be some caveats. Silymarin is usually sold as an 80% extract. The other plant substances present may affect the process in some unpredictable way. I've not used cyclodextrin myself, though the description from those who have indicate the method should wrk, if the mixture is stirred vigorously. Cyclodextrin does not work as a detergent (one end charged,, one end neutral, so it can bond to both insoluble substances and to water.) Cyclodextrin molecules form a ring which traps other molecules, and acts as a carrier: it is water soluble, and so carries insoluble molecules along for the ride, so to speak.

I intend to try Miralax and silymarin within the next few days. I'll report back, if someone (Bixbyte? Lucid?) doesn't beat me to it.[/quote]

[bixbyte]

Sorry to rain on the parade but there is a big concern for me with silymarin. It has been shown to be pro estrogen. Not only being estrogenic in and of itself but also to promote the action of endogenous estrogen. Here is a selected article though there are numerous ones just google estrogen estrogenic and silymarin or milk thistle.

Silymarin as a Estrogen agonist

I do take milk thistle but don't think that taking huge dosages would be very good for males. Resveratrol has been shown to be anti-estrogen which is another reason for men to want to use it.

Another Reference Showing Silymarin as a Pro-Estrogen Compound

Edward,

I have read the same Estrogen effect in some studies for Resveratrol:

The similarity in structure between resveratrol and diethylstilbestrol (a synthetic estrogen) has prompted investigations into resveratrol's potential as a phytoestrogen (a plant compound that produces estrogen-like effects). However, these properties also stimulate the growth of human breast cancer cells [5]. This finding seems contrary to its other anticancer activities, and is a cause for concern.

Alex

[edward]

Alex,

I read the article that I think you are referring to a while back when I looked into resveratrol and estrogen , here is a link to the full text.

http://cancerres.aac.../61/20/7456.pdf

It mentions that resveratrol is an anti-estrogen (antagonist) at the Alpha Estrogen receptors and a pro-estrogen (agonist) at the Beta Estrogen receptors. At the time that I read this article I concluded, that along with everything else that I had read that the net effect in a human male would be an over all Anti-Estrogen effect. Looking back at this article by itself I can see how there might be a problem. Its been awhile since I looked into this and if I have time I might sit down and read through all of the estrogen and resveratrol articles again and re-evaluate my conclusion.

However I am completely convinced that Silymarin is very estrogenic (pro-estrogen) and therefore am concerned about high doses.

-E

[maxwatt]

Specific studies of estrogen and silymarin I can find do not show a strong estrogenic effect one way or another. See below. What do you base your conviction f estrogenic effect on?

Toxicology. 2005 Nov 5;215(1-2):80-9. Epub 2005 Aug 1. Links
Effects of silymarin flavonolignans and synthetic silybin derivatives on estrogen and aryl hydrocarbon receptor activation.Plísková M, Vondrácek J, Kren V, Gazák R, Sedmera P, Walterová D, Psotová J, Simánek V, Machala M.
Veterinary Research Institute, Brno, Czech Republic.

Silymarin, a standardized mixture of flavonolignans, or its major constituents could be effective for prevention and treatment of hepatic damage or skin cancer. However, their potential side effects, such as modulation of endocrine functions via the disruption of estrogen receptor (ER) and/or aryl hydrocarbon receptor (AhR) activation, are largely unknown. In the present study, we investigated impact of silymarin, its constituents and a series of their synthetic derivatives on ER- and AhR-mediated activities using in vitro reporter gene assays. We found that none of the compounds under study affected the AhR-mediated activity in rat hepatoma cells. Contrary to that, several compounds behaved as either partial or full ER agonists. Silymarin elicited partial ER activation, with silybin B being probably responsible for a majority of the weak ER-mediated activity of silymarin; silybin A and other flavonolignans were found to be inactive and potent ER agonist taxifolin is only a minor constituent of silymarin. To our knowledge, this is probably the first time, when receptor-specific in vitro effects of separated diastereomers have been demonstrated. In contrast to silymarin constituents, the synthetic silybin derivatives, potentially useful as chemoprotective agents, did not modulate the ER-mediated activity, with exception of 23-O-pivaloylsilybin. Interestingly, 7-O-benzylsilybin potentiated ER-mediated activity of 17beta-estradiol despite possessing no estrogenic activity. In conclusion, our data suggest that estrogenicity of some silymarin constituents should be taken in account as their potential side effect when considered as chemopreventive compounds. These results also stress the need to study biological activities of purified or synthesized diastereomers of silybin derivatives.

PMID: 16076518
--------------

J Steroid Biochem Mol Biol. 2003 Aug;86(2):179-88. Links
Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx) rats.Seidlová-Wuttke D, Becker T, Christoffel V, Jarry H, Wuttke W.
Department of Clinical and Experimental Endocrinology, University of Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany.

Silymarin is a widely used standardized mixture of flavonolignans and its major component Silybinin binds to cytosolic estrogen receptors. Here, we demonstrate that this binding is exclusive to the estrogen receptor beta (ERbeta). Treatment of ovariectomized (ovx) rats with silymarin or estradiol (E2) may allow differentiation of biological effects mediated by the ERalpha or ERbeta. E2 inhibited serum LH, cholesterol, LDL and HDL concentrations in the blood and increased gene expression of IGF1, HbEGF and C3 in the uterus, while silymarin was totally ineffective or antagonistic in altering these parameters. Both, E2 and silymarin inhibited expression of uterine ERbeta gene. Hence, in the pituitary, liver (where the lipoproteins are synthesized) and uterus E2 acts primarily via the ERalpha. Exclusive estrogenic effects of silymarin were observed in the metaphysis of the femur (MF), on osteoblast parameters (gene expression of IGF1, TGFbeta1, osteoprotegerin, collagen-1alpha1, osteocalcin (OC)) and on the osteoclast activity marker tartrate resistant acid phosphatase (TRAP) gene expression of adult ovx rats. Our RT-PCR method detects ERbeta gene expression in all organs including developing bones but not in the MF of adult ovx rats. We conclude therefore, that the effects of silymarin in this part of the bone cannot be exerted via the ERalpha because it does not bind to this receptor subtype. Despite the failure to detect ERbeta mRNA in the MF of our animals the possibility exists that ERbeta protein is present and may mediate the effects of silymarin. Another possibility may be that the effect of silymarin and therefore possibly also of E2 in the MF may be mediated via other possibly not yet identified receptors or via an ERbeta splice variant which is not detected by our PCR-method.

PMID: 14568570

[inawe]

Seems that the bioavailability of silybin is not that good. But there
is a compound by the name of Silipide (Siliphos) of silybin and
lecithin.
According to some papers the bioavailability increases 10 fold. For
example, in PMID: 17348898 [PubMed - indexed for MEDLINE]:
"These data show that a phytosome complex of phosphatidylcholine and
silybin markedly enhances bioavailability in dogs."
I couldn't find a website of the manufacturer Siliphos, or see
anywhere the proportion of lecithin to silybin. I'll like to know if it's just a mixture
or what it takes to make that "phytosome complex".

Correction: Siliphos is the trade name, not the manufacturer.

[sdxl]

I did a little research on Siliphos a few years ago. Manufacturing involves nasty solvents as I can recall. Not something you can easily do at home. Search the US patent database. It's made by Indena btw.

[inawe]

I did a little research on Siliphos a few years ago. Manufacturing involves nasty solvents as I can recall. Not something you can easily do at home. Search the US patent database. It's made by Indena btw.

Wont try. I already blew my kitchen sink mixing something else.
Silipide was invented by S. Malandrino and G. Pifferi, Drugs Future,
15, 226-227 (1990). See also PMID: 8149949.

[curious_sle]

It would seem NSI offers Siliphos. Now if i trusted them... also Natural Factors has a product at 21$ for 45x 100mg plus other stuff.

[health_nutty]

Anyone else taking high dose silymarin because of this study?

[lucid]

i take about 800 mg / day 400 in the morning and 400 in the evening