m1t: The quick and dirty guide to using it

[bobbydigital07]

*Testicular atrophy a.k.a my balls are shrinking :
Yes, this is a common side effect of using any prohormone. However this is nothing to worry about. Under normal circumstances, you will get back to your normal size after the PCT.
Incase of extreme cases the following can be tried.
Day 1 Clomid @ 300mg
Week 5 Clomid @ 100mg
Week 5/6 Clomid @ 50mg

To the best of my knowledge this has cured most cases of testicular atrophy.

yes, i deff need some of this, this happens to me with any prohormone, where can i get some clomid?

[gymnast212]

is M1T even worse for people that are still in their teens?? cause a buddy of mine took it for about 3 weeks...and said the only side effects he had were his nipples. And he said the pumps and gains from it were amazing. Couldn't M1T be relatively safe if you do it correcty? but still, i doubt it could be that good for people my age, health wise. Also, is it considered a test booster a PH or what? i

m not even thinkin about using it, just lookin out for a buddy cause he wants to do another cycle. what are some safer test boosters that he could use. (Do people my age, 18, even need test, considering now is the time our test is highest)...?

[gymnast212]

bump it

[Squacher]

bump

[nitrous]

is M1T even worse for people that are still in their teens?? cause a buddy of mine took it for about 3 weeks...and said the only side effects he had were his nipples. And he said the pumps and gains from it were amazing. Couldn't M1T be relatively safe if you do it correcty? but still, i doubt it could be that good for people my age, health wise. Also, is it considered a test booster a PH or what? i

m not even thinkin about using it, just lookin out for a buddy cause he wants to do another cycle. what are some safer test boosters that he could use. (Do people my age, 18, even need test, considering now is the time our test is highest)...?

at 18 do you really need to worry about test boosters? injecting actual test is more safe than m1-t...you tell me if its worth it...

[daponik]

Bump. So...is anyone still using M1T?

[Estopell]

Bump. So...is anyone still using M1T?

Nope, they don't like having huge muscles with yellow eyes.

[ayomo]

Bump. So...is anyone still using M1T?

starting a 2-3 week cycle over the summer. gotta plan it out first and get some stuff together.

[daponik]

Nope, they don't like having huge muscles with yellow eyes.

Phew...finishing up the last few days of a 4-week cycle. I did really good in my training and nutrition this time around and gained 13 pounds. Now to see how much I actually keep over the next few weeks.

Anyway, I don't have access to Clomid or HCG, so here's to hoping that OTC Gaspari Novedex XT suffices for PCT. Guess I'm gonna be the guinea pig on this one.

[prickleferret]

i don't think that Novadex XT will be enough. i am surprised you only got 13 pounds off it. while that is good, every M1 T cycle i ever did gave me 20 pounds or more and i have kept it all. oh well, maybe i just respond better to it. you may be in for some vicious sides with only Novadex XT for your PCT.

[daponik]

i don't think that Novadex XT will be enough. i am surprised you only got 13 pounds off it. while that is good, every M1 T cycle i ever did gave me 20 pounds or more and i have kept it all. oh well, maybe i just respond better to it. you may be in for some vicious sides with only Novadex XT for your PCT.

Thanks for the feedback, ferret. I got one more weigh in this Monday, I'm hoping I might get a few more pounds. I started at 180 and was hoping to hit 200 with this cycle. As of now, 195 seems more realistic. I should have mentioned that I have been training for several years and this is not my first cycle of M1T, but this is the one I've been most consistent on.

You think I should be worried during PCT? Man, the sides are killing me now. Headaches, nosebleeds, lack of sex drive, lethargy...about the only thing I didn't get this cycle was the sore nipples. I guess I better get off BB.com for a lil bit and go find me some Clomid then.

[prickleferret]

dude, if your sides are that bad, maybe you shouldn't be taking it. i know everyone wants the quickest way to size and strength but when you get sides like you are describing, it may be time to look into something else. i never got a single side effect from M1 T. i am lucky though. definitely get some Nolva for your PCT too. if you go on to do another cycle of it in a few months, keep an eye on your lower back. if you are experiencing crippling lower back pain too, immediately increase your water intake. that pain is your kidneys telling you you need more water. i used to get that from time to time on M1 T. all things said, i would stay away from M1 T if it is doing these things to you. just my opinion.

[Estopell]

Thanks for the feedback, ferret. I got one more weigh in this Monday, I'm hoping I might get a few more pounds. I started at 180 and was hoping to hit 200 with this cycle. As of now, 195 seems more realistic. I should have mentioned that I have been training for several years and this is not my first cycle of M1T, but this is the one I've been most consistent on.

You think I should be worried during PCT? Man, the sides are killing me now. Headaches, nosebleeds, lack of sex drive, lethargy...about the only thing I didn't get this cycle was the sore nipples. I guess I better get off BB.com for a lil bit and go find me some Clomid then.

How old are you? Please tell me you'll be taking Nolva for PCT.

[animalfan]

How old are you? Please tell me you'll be taking Nolva for PCT.

he's only got novadex xt from gaspari. sounds like blood pressure is giving him nosebleeds and headaches. wonder if he's used any support supps during his cycle, or what the m1t dose is...

[ayomo]

Thanks for the feedback, ferret. I got one more weigh in this Monday, I'm hoping I might get a few more pounds. I started at 180 and was hoping to hit 200 with this cycle. As of now, 195 seems more realistic. I should have mentioned that I have been training for several years and this is not my first cycle of M1T, but this is the one I've been most consistent on.

You think I should be worried during PCT? Man, the sides are killing me now. Headaches, nosebleeds, lack of sex drive, lethargy...about the only thing I didn't get this cycle was the sore nipples. I guess I better get off BB.com for a lil bit and go find me some Clomid then.

you need nolva (tamoxifin citrate) for pct that is a 100% must for m1t cycles, clomid i didnt need but if my nuts would have shrank i had some on hand.

like above poster said headaches and nosebleeds are from high blood pressure, hawthorn berries should have been preloaded before cycle and taken during, i have a home bp tester that I use while on cycle and dose my hawthorn berries accordingly.

letharty is one of the big sides of m1t, are you taking it by itself or stacking it with something?

your sex drive will be dead thats a for sure, the nova i mentioned earlier will help that, so will clomid.

whats your dosage at? you been taking milk thistle? your lowerback will start hurtnig soon from your kidneys and liver.

just a few pct supps i took were retain, fenugreek, zma, dhea, perfect cycle and a few more did you do any research before you started this cycle and by research i dont mean, oh this guy took m1t and gained 20lbs.

good luck man, hope you can have kids some day

[daponik]

you need nolva (tamoxifin citrate) for pct that is a 100% must for m1t cycles, clomid i didnt need but if my nuts would have shrank i had some on hand.

like above poster said headaches and nosebleeds are from high blood pressure, hawthorn berries should have been preloaded before cycle and taken during, i have a home bp tester that I use while on cycle and dose my hawthorn berries accordingly.

letharty is one of the big sides of m1t, are you taking it by itself or stacking it with something?

your sex drive will be dead thats a for sure, the nova i mentioned earlier will help that, so will clomid.

whats your dosage at? you been taking milk thistle? your lowerback will start hurtnig soon from your kidneys and liver.

just a few pct supps i took were retain, fenugreek, zma, dhea, perfect cycle and a few more did you do any research before you started this cycle and by research i dont mean, oh this guy took m1t and gained 20lbs.

good luck man, hope you can have kids some day

Reps to you, brother. Thanks for looking out for me. I did finally order the Clomid last nite...yes, ball shrinkage was evident after the first week.

The headaches were very mild, nothing that I had to take anything for, but they were there...not enough for me to miss work or workouts. Hawthorne berry, saw palmetto, and milk thistle started in mid-cycle helped alleviate all of those sides, though, so the last week and a half has been pretty good. I only had the lower back pain once, but it was before I introduced all these other supps, plus I just increased my water intake, that helped a lot.

The nosebleeds were nothing really. Not even bleeding really. Just noticed some small dried blood spots if I ever blew or cleaned my nose. I'm not stacking it with anything else. Just a good high-protein diet and my vitamin packs and lots of rest.

Sex drive has been diminished - went from doing it EOD to once or twice a week during this cycle. You can bet my wife was glad I told her I was coming off-cycle soon and the Clomid I was getting would help. I forgot to mention earlier (I'll edit my profile after this) that I'm 34, been training for almost 10 years, and already have 4 kids. ;-) so that is a little less of a worry.

But now you got me thinking I should have bought that liquid Nolva last night when I got the Clomid. I was thinking I'd only need one or the other.

Dose was 10mg/day, split into 2 doses during week one 1 and 4. 15mg/day during week 2 and 3, split into 3 doses per day.

I look forward to continued discussion on this.

[ayomo]

about that nolva, id never do pct w/o using it

gl with everything

[Krzna]

Reps to you, brother. Thanks for looking out for me. I did finally order the Clomid last nite...yes, ball shrinkage was evident after the first week.

The headaches were very mild, nothing that I had to take anything for, but they were there...not enough for me to miss work or workouts. Hawthorne berry, saw palmetto, and milk thistle started in mid-cycle helped alleviate all of those sides, though, so the last week and a half has been pretty good. I only had the lower back pain once, but it was before I introduced all these other supps, plus I just increased my water intake, that helped a lot.

The nosebleeds were nothing really. Not even bleeding really. Just noticed some small dried blood spots if I ever blew or cleaned my nose. I'm not stacking it with anything else. Just a good high-protein diet and my vitamin packs and lots of rest.

Sex drive has been diminished - went from doing it EOD to once or twice a week during this cycle. You can bet my wife was glad I told her I was coming off-cycle soon and the Clomid I was getting would help. I forgot to mention earlier (I'll edit my profile after this) that I'm 34, been training for almost 10 years, and already have 4 kids. ;-) so that is a little less of a worry.

But now you got me thinking I should have bought that liquid Nolva last night when I got the Clomid. I was thinking I'd only need one or the other.

Dose was 10mg/day, split into 2 doses during week one 1 and 4. 15mg/day during week 2 and 3, split into 3 doses per day.

I look forward to continued discussion on this.

u want the killer? if u r ready to spend some money, get some cialis and dostinex. Try it and thank me later. **** it reduces prolactin like crazy and gets to to multiple orgasms. Your wife will look at you in awe , trust me , mine does

[Lynch22]

I've been on 5mg of underground lab M1T for one week and I feel like crap. The lethargy is severe. My nipples are tender and the left is starting to look puffy. I need some advice on PCT, how much nolva and 6oxo to take for only a short time being on M1T. Without 4ad this stuff is useless.

[Kevin N]

I tried emailing and Pm'ing Krzna but his mailbox is full. Where can I purchase Nolvadex online?

[Thunder KAT]

wow great thread KRZNA! lots of good info and yea u should deff. do some more threads for other PH'S/AAS i think providing info like this to everyone on the forms is very beneficial!! keep up the good work!

[Carmen0857]

u want the killer? if u r ready to spend some money, get some cialis and dostinex. Try it and thank me later. **** it reduces prolactin like crazy and gets to to multiple orgasms. Your wife will look at you in awe , trust me , mine does

Makes sense because prolactin rises rigth after an orgasm, If there is too much prolactin preasent one will not be able to maintain an erection, I beleive this is called the "refractory period."

[SKYWALKER09]

FYI brotha's....Toremifene is also getting great reviews as a SERM for PCT. I know I got mine on the way to try instead of nolva or clomid. Research it biottch.

Except you KRNZA, you already know all dis shizzy.

[Krzna]

Makes sense because prolactin rises rigth after an orgasm, If there is too much prolactin preasent one will not be able to maintain an erection, I beleive this is called the "refractory period."

RF is immediately after sex in men and prolonged durin periods of pregnancy and sometimes during lactation in women. Coming to think of it, viagra+dostinex maybe better than cialis and dostinex. That way you are not only a porn star but also an energiser bunny.

Think of this
Clomid+Dostinex+Vialis (50/50-tadafil/via) + some argenine + yohimbine bark etc + maca


I can paint my woman white and give my celing a new coat too

[zfactor2004]

i was told (and sold) by a competing site a while back the ul m1t they also told me to use and stack it with methyl rage?? this is a 17?? why would they have told me this? anyone...

[budlight1]

If you think that milk thistle and other herbal supplements will acctually help your liver then you are a moron. Show me one scientific study where milk thistle or any of the liver supplements do anything

[Krzna]

If you think that milk thistle and other herbal supplements will acctually help your liver then you are a moron. Show me one scientific study where milk thistle or any of the liver supplements do anything

show me a study where milk thistle or other herbal dont do anything and i will show u 10 studies where they do a lot of benefit to liver health.

Mr wise ass ...

[Krzna]

You asked for one, i give you five. Now reply



University Institute Of Pharmaceutical Sciences, Panjab University, Chandigarh, India.

The aim of the present study was to study the synergistic hepatoprotective effect of silymarin with phospholipids when it is encaged in microspheres so as to passively target it to liver and to compare these silymarin formulations with silymarin solution. Various silymarin loaded lipid emulsions were formulated which include formulation A prepared with soyabean oil as an internal oily phase, soya lecithin as surfactant and tween 80 as cosurfactant; formulation B which was same as formulation A but was filtered through 0.45 micro membrane filter and finally steam sterilized for intravenous administration; formulation C containing soyabean oil as an internal oily phase, soya lecithin as surfactant, tween 80 and propylene glycol as cosurfactant/ cosolvent. These formulations were compared for their release profile with silymarin solution in propylene glycol, i.e. formulation D. In vivo evaluation was carried out using three models i.e. phenobarbitone induced sleep time in mice, biochemical estimation of SGOT and SGPT enzyme levels and histopathological examination of rat livers. Results revealed that there was significant reduction in sleep time in the mice treated with silymarin loaded lipid microspheres (both p.o. as well as i.v.) when compared with control and even with plain lipid microspheres and silymarin solution and significant reduction in enzyme levels in silymarin lipid microspheres treated group when compared with control, plain lipid microspheres as well as silymarin solution treated group. Histopathological studies also supported the results obtained from the other two models. A positive outcome of these studies gave an insight that if silymarin is coupled with phospholipid in such microparticulate delivery systems, hepatoprotective effect of drug molecules can be pronounced further by self targeting nature and synergistic action.



http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract


Silymarin inhibits TNF-alpha-induced expression of adhesion molecules in human umbilical vein endothelial cells.
FEBS Lett. 2003 Aug 28;550(1-3):89-93.
Silymarin is known to have an anti-atherosclerotic activity, but the mechanism responsible for it remains unclear. Here, we demonstrate a possible mechanism involved in the anti-atherosclerotic activity of silymarin. Silymarin inhibited THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs). Silymarin also suppressed the TNF-alpha-induced protein and mRNA expression of adhesion molecules, such as VCAM-1, ICAM-1 and E-selectin, in HUVECs. Moreover, silymarin suppressed the TNF-alpha-induced DNA binding of NF-kappaB/Rel in HUVECs. Taken together, these results demonstrate that silymarin exerts an anti-atherosclerotic activity, at least in part, by inhibiting the expression of adhesion molecules.

Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation.
Eur J Neurosci. 2002 Dec;16(11):2103-12.
An inflammatory response in the central nervous system mediated by activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. Silymarin is a polyphenolic flavonoid derived from milk thistle that has anti-inflammatory, cytoprotective and anti-carcinogenic effects. In this study, we first investigated the neuroprotective effect of silymarin against lipopolysaccharide (LPS)-induced neurotoxicity in mesencephalic mixed neuron-glia cultures. The results showed that silymarin significantly inhibited the LPS-induced activation of microglia and the production of inflammatory mediators, such as tumor necrosis factor-alpha and nitric oxide (NO), and reduced the damage to dopaminergic neurons. Therefore, the inhibitory mechanisms of silymarin on microglia activation were studied further. The production of inducible nitric oxide synthase (iNOS) was studied in LPS-stimulated BV-2 cells as a model of microglia activation. Silymarin significantly reduced the LPS-induced nitrite, iNOS mRNA and protein levels in a dose-dependent manner. Moreover, LPS could induce the activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase but not extracellular signal-regulated kinase. The LPS-induced production of NO was inhibited by the selective p38 MAPK inhibitor SB203580. These results indicated that the p38 MAPK signaling pathway was involved in the LPS-induced NO production. However, the activation of p38 MAPK was not inhibited by silymarin. Nevertheless, silymarin could effectively reduce LPS-induced superoxide generation and nuclear factor kappaB (NF-kappaB) activation. It suggests that the inhibitory effect of silymarin on microglia activation is mediated through the inhibition of NF-kappaB activation.

Treatment of silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin.
Int J Oncol. 2002 Dec;21(6):1213-22. Katiyar SK.
University of Alabama at Birmingham, Birmingham, AL.
It is well documented that ultraviolet (UV) light-induced immune suppression and oxidative stress play an important role in the induction of skin cancers. Earlier, we have shown that topical treatment of silymarin, a plant flavonoid from milk thistle (Silybum marianum), to mouse skin prevents photocarcinogenesis, but the preventive mechanism of photocarcinogenesis in vivo animal system by silymarin is not well defined and understood. To define the mechanism of prevention, we employed immunostaining, analytical assays and ELISA which revealed that topical treatment of silymarin (1 mg/cm2 skin area) to C3H/HeN mice inhibits UVB-induced suppression of contact hypersensitivity (CHS) response to contact sensitizer dinitrofluorobenzene. Prevention of UVB-induced suppression of CHS by silymarin was found to be associated with the inhibition of infiltrating leukocytes, particularly CD11b+ cell type, and myeloperoxidase activity (50-71%). Silymarin treatment also resulted in significant reduction of UVB-induced immunosuppressive cytokine interleukin-10 producing cells and its production. Topical treatment of silymarin also resulted in significant reduction of the number of UVB-induced H2O2 producing cells and inducible nitric oxide synthase expressing cells concomitant with decrease in H2O2 (58-65%) and nitric oxide (65-68%) production. Together, these data suggest that prevention of UVB-induced immuno-suppression and oxidative stress by silymarin may be associated with the prevention of photocarcinogenesis in mice. The data obtained from this study also suggest: i) phase-I clinical trial of silymarin in high skin cancer risk human population and ii) development of sunscreen containing silymarin as an antioxidant (chemopreventive agent) or silymarin can be supplemented in skin care products.

[Krzna]

A flavonoid antioxidant, silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells.
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Cancer Res. 1998 May 1;58(9):1920-9.
Prostate cancer (PCA) is the most common nonskin malignancy and the second leading cause of cancer deaths in United States males. One practical and translational approach to control PCA is to define a mechanism-based anti-carcinogenic agent(s). Recently, we showed that silymarin, a flavonoid antioxidant isolated from milk thistle, possesses exceptionally high to complete protective effects against experimentally induced tumorigenesis. Because the epidermal growth factor receptor (erbB1) and other members of the erbB family have been shown to play important roles in human PCA, efforts should be directed to identify inhibitors of this pathway for PCA intervention. In this study, we assessed whether silymarin inhibits erbB1 activation and associated downstream events and modulates cell cycle regulatory proteins and progression, leading to growth inhibition of human prostate carcinoma DU145 cells. Treatment of serum-starved cells with silymarin resulted in a significant inhibition of transforming growth factor alpha-mediated activation of erbB1 but no change in its protein levels. Silymarin treatment of cells also resulted in a significant decrease in tyrosine phosphorylation of an immediate downstream target of erbB1, the adapter protein SHC, together with a decrease in its binding to erbB1. In the studies analyzing cell cycle regulatory molecules, silymarin treatment of cells also resulted in a significant induction of cyclin-dependent kinase inhibitors (CDKIs) Cip1/p21 and Kip1/p27, concomitant with a significant decrease in CDK4 expression, but no change in the levels of CDK2 and CDK6 and their associated cyclins E and D1, respectively. Cells treated with silymarin also showed an increased binding of CDKIs with CDKs, together with a marked decrease in the kinase activity of CDKs and associated cyclins. In additional studies, treatment of cells grown in 10% serum with anti-epidermal growth factor receptor monoclonal antibody clone 225 or different doses of silymarin also resulted in significant inhibition of constitutive tyrosine phosphorylation of both erbB1 and SHC but no change in their protein levels. Furthermore, whereas silymarin treatment resulted in a significant increase in the protein levels of both Cip1/p21 and Kip1/p27, monoclonal antibody 225 showed an increase only in Kip1/p27. These findings suggest that silymarin also inhibits constitutive activation of erbB1 and that the observed effect of silymarin on an increase in CDKI protein levels is mediated via inhibition of erbB1 activation only in the case of Kip1/p27; however, additional pathways independent of inhibition of erbB1 activation are possibly responsible for the silymarin-caused increase in Cip1/p21 in DU145 cells. In other studies, silymarin treatment also induced a G1 arrest in the cell cycle progression of DU145 cells and resulted in a highly significant to complete inhibition of both anchorage-dependent and anchorage-independent growth of DU145 cells in a dose- and time-dependent manner. Taken together, these results suggest that silymarin may exert a strong anticarcinogenic effect against PCA and that this effect is likely to involve impairment of erbB1-SHC-mediated signaling pathway, induction of CDKIs, and a resultant G1 arrest.

Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients.
J Hepatol. 1997 Apr;26(4):871-9.
Several studies have demonstrated that diabetic patients with cirrhosis require insulin treatment because of insulin resistance. As chronic alcoholic liver damage is partly due to the lipoperoxidation of hepatic cell membranes, anti-oxidizing agents may be useful in treating or preventing damage due to free radicals. The aim of this study was to ascertain whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis. METHODS: A 12-month open, controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis. One group (n=30) received 600 mg silymarin per day plus standard therapy, while the control group (n=30) received standard therapy alone. The efficacy parameters, measured regularly during the study, included fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria levels, glycosylated hemoglobin (HbA1c) and malondialdehyde levels. RESULTS: There was a significant decrease in fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria and HbA1c levels already after 4 months of treatment in the silymarin group. In addition, there was a significant decrease in fasting insulin levels and mean exogenous insulin requirements in the treated group, while the untreated group showed a significant increase in fasting insulin levels and a stabilized insulin need. These findings are consistent with the significant decrease in basal and glucagon-stimulated C-peptide levels in the treated group and the significant increase in both parameters in the control group. Another interesting finding was the significant decrease in malondialdehyde/levels observed in the treated group. CONCLUSIONS: These results show that treatment with silymarin may reduce the lipoperoxidation of cell membranes and insulin resistance, significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration.

[Krzna]

Next time, think before u type.

Research studies conducted in the laboratory have investigated the properties of silymarin or its isomer silibinin using cell lines and animal models. Other substances in milk thistle have not been extensively studied.

Several research studies have investigated the effects of silymarin or silibinin in a noncancer context. These studies have tested silymarin or silibinin:

* In healthy animal liver and kidney cells.
* As a prophylaxis against toxic chemicals.
* In stimulating detoxification pathways (enzyme concentrations and activity).
* For antioxidant properties.

Silymarin or silibinin has also been investigated in cancer models. The effects of silymarin and/or silibinin have been invested in prostate (DU 145, LNCaP, PC-3),[1-5] breast (MDA-MB 468, MCF-7),[6-8] hepatic (HepG2),[9,10] epidermoid (A431),[10] colon (Caco-2),[11] ovarian (OVCA 433, A2780),[12] histiocytic lymphoma (U-937),[13] and leukemia (HL-60) [14,15] cells. In animal tumor models, tongue cancer,[16] skin cancer,[17-22] bladder cancer,[23] and adenocarcinoma of the colon [24,25] and small intestine [25] have been investigated. These studies have tested the ability of silymarin or silibinin to:

* Mitigate the toxicity associated with chemotherapy agents.
* Enhance the efficacy of chemotherapy agents.
* Inhibit the growth of cancer cell lines and inhibit tumor initiation or tumor promotion.

Although many of these studies have produced encouraging results, none of the findings have been replicated in human clinical trials.

Laboratory data suggest that silymarin and silibinin protect the liver from damage induced by toxic chemicals. Animal studies have found that liver cells treated with silibinin and then exposed to toxins do not incur cell damage or death at the same rate as liver cells that are not treated with silibinin. This finding suggests that silibinin can prevent toxins from entering the cell or effectively exports toxins out of the cell before damage ensues.[10,26-30] Alternatively, this may be related to the effect of silymarin on detoxification systems. In vitro data have shown silibinin to stimulate and/or inhibit phase I detoxification pathways in silibinin-treated human liver cells. However, this effect was found to be dose-dependent, and these levels are not physiologically attainable with the current dose recommendations.[31,32]

Silymarin has been shown to stimulate phase II detoxification pathways in mice. Administration of silymarin (100 or 200 mg/kg body weight/day) to SENCAR mice for 3 days significantly increased glutathione S-transferase activity in the liver (P <.01-.001), lung (P <.05-.01), stomach (P <.05), small bowel (P <.01), and skin (P <.01). This effect appeared to be dose-dependent.(9) Administration of silymarin to rats challenged with a toxin (50 mg/kg body weight) resulted in higher levels of glutathione in liver cells, decreased levels of oxidative stress (measured by malondialdehyde concentrations), and less elevated liver function tests (measured by levels of serum glutamic-oxaloacetic transaminase [SGOT] and serum glutamate pyruvate transaminase [SGPT]).[30] Silymarin and silibinin have also been found to accelerate cell regeneration in the liver through stimulation of precursors to DNA synthesis and enhancement of production of the cellular enzymes required for synthesis of DNA.[33-38] Laboratory studies have also shown silymarin and silibinin to be potent antioxidants.[27,28,39-46] Silymarin has been shown to mitigate oxidative stress in cells treated with pro-oxidant compounds.

A number of laboratory studies have investigated the effect of silymarin or silibinin on the efficacy and toxicity of chemotherapy agents or have measured their direct cytotoxic activity. In an investigation of the effect of a variety of flavonoids on the formation of DNA damage, silymarin did not induce DNA damage in colon (Caco-2) cells, hepatoma (HepG2) cells, and human lymphocytes.[11] At higher concentrations of silymarin (400-1,000 μmol/L), DNA damage was induced in an epithelial cell line (HeLa cells). At higher concentrations (1,000 μmol/L), DNA damage was observed in human lymphocytes. Cell growth was inhibited as the flavonoid concentration was increased in human lymphocytes and HeLa cells. Only at very high concentrations was cell viability affected by silymarin in HepG2 cells. Although this study demonstrated that flavonoids are capable of inhibiting cellular proliferation and inducing DNA strand breaks, the results were obtained at very high concentrations that may be difficult to achieve in humans. This study also showed that silymarin does not stimulate cell growth in the HeLa, Burkitt’s lymphoma, and human hepatoma cell lines.

Silymarin has also been investigated as a possible adjunctive agent in mitigating some of the toxicity associated with chemotherapy agents. Silibinin and silychristin exerted a protective effect on monkey kidney cells exposed to vincristine and especially cisplatin chemotherapy.[47] Silibinin (200 mg/kg body weight) administration with cisplatin in rats resulted in statistically significant reductions in measures of kidney toxicity.[48] Significant decreases in weight loss, faster recovery of urinary osmolality measures, and depressions in the increase in activity of urinary alanine aminopeptidase (AAP, a marker of kidney toxicity) were observed. Silibinin had no effect on magnesium excretion or glomerular function. Silibinin (2 g/kg body weight) administration in rats receiving cisplatin prevented reductions in creatinine clearance, increases in urea plasma levels, and large increases in urinary AAP.[49] No effect on magnesium excretion was observed. Silibinin did not interfere with the antineoplastic effects of cisplatin or ifosfamide in germ cell tumors. In experiments with ovarian and breast cancer cell lines, silibinin potentiated the effect of cisplatin and doxorubicin.[12] IdB 1016, a form of silibinin bound to a phospholipid complex, was found to enhance the activity of cisplatin against A2780 ovarian cancer cells, but had no effect on its own.[50] Silibinin may increase the chemosensitivity of DU 145 prostate cancer cells resistant to chemotherapy.[51]

Studies have also investigated the effect of silymarin on tumor initiation and promotion. Silymarin appears to have a chemopreventive effect through perturbations in the cell cycle, altering cell-to-cell signaling that induces cellular proliferation, affecting angiogenesis, or through its anti-inflammatory properties.[1,6,12,18,52] These findings have been supported in human prostate, breast, ectocervical, ovarian, hepatic, leukemia, and epidermoid cell lines.[4,6,8,9,14,53] An investigation of the effect of silymarin on ultraviolet B (UVB) radiation-induced nonmelanoma skin cancer in mice found that silymarin treatment significantly reduced tumor incidence (P <.003), tumor multiplicity (P <.0001), and tumor volume (P <.0001) in cells treated with UVB to induce tumor promotion, but not in cells treated with UVB to induce tumor initiation.[18] These findings suggest that silymarin plays a more prominent role in the progression of cancer cells, rather than preventing the formation of cancer cells. A number of studies have investigated the mechanism through which silymarin may affect tumor promotion in mouse skin tumor models. Studies have found that silymarin reduces transcription of markers of tumor promotion and activity,[18] inhibits transcription of tumor promoters,[54] stimulates antioxidant activities,[18,22] interferes with cell-to-cell signaling,[53] inhibits inflammatory actions,[18,21] and modulates cell-cycle regulation.[55]

In prostate cancer cell lines, silibinin has been shown to inhibit growth factors and signaling that stimulate cell growth,[1-3,5] promote cell cycle arrest,[1,4] and inhibit antiapoptotic activity.[51] In rats with azoxymethane-induced colon cancer, dietary silymarin resulted in a reduction in the incidence and multiplicity of adenocarcinoma of the colon in a dose-dependent manner.[24,25] Dietary silymarin had no effect on small intestinal adenocarcinoma,[25] but exerted a preventive effect in mice with N-butyl-N-(4-hydroxybutyl) nitrosamine–induced bladder cancer [23] and in F344 rats with 4-nitroquinoline 1-oxide–induced cancer of the tongue.[16] Dietary silibinin administered to rats with prostate carcinoma increased production of insulin-like growth factor-binding protein-3 in the plasma of rats and significantly inhibited tumor volume (P <.05).[2]