Milk thistle

[Wileyl]

Any one been taking milk thistle with stage 4 prostate cancer and seeing good results?

[teamkv]

Giving it to my husband. On the CT scan the doc said there was perhaps a bit of liver issues so I started him on it for that. I have heard that the life extension brand has something in it that is good for Prostate cancer

[teamkv in reply to teamkv]

I have read on here though not to take it with Zytiga

[CalBear74 in reply to teamkv]

I believe you are referring to isosylibin A and B, both of these can be the basis of searches at pubmed.gov. You will also find this informative, albeit marketing literature:

lifeextension.com/Magazine/...

[HopingForTheBest1]

Just in case you had not seen the below post from several months ago -

Abiraterone & Milk Thistle not a good combo

ronton2•

10 months ago•21 Replies

I am on the new protocol for PCa: Lupron w Zytiga. A friend suggested that I add milk thistle to enhance liver protection as these drugs can effect liver function. After two days adding this to my regimen I thought to call the pharmacist where my oncologist practices (Seattle Cancer Care Alliance). Word back: milk thistle might inhibit the metabolism of abiraterone, meaning it could lead to an increased concentration of the drug in my system, putting me at risk for more or increased side effects. Suffice it to say, I have stopped the milk thistle. Latest PSA: Lowest since I was diagnosed in 2005 @0.0- I can only hope this continues into the future.

[snoraste]

I have been taking it with Zytiga with little discernible side effects. I have not seen the study mentioned above about the interaction between Zytiga and milk thistle. Be curious to see it.

[Thinus]

Hallo Wiley

I take the milkthistle/dandelion combo.

Attached a copy out of the Livestrong website:

In animal research, silibinin was found to exert cancer-fighting effects against an advanced form of human prostate tumor cells, resulting in decreased proliferation and increased cancer-cell apoptosis.123Silibinin has high bioavailability in the prostate after oral administration, and scientists concluded that it has strong potential to be developed as an intervention for hormone-refractory (castration-resistant) human prostate cancer.121 Silibinin may also work synergistically with the chemotherapy drug doxorubicin to help kill cancer cells, making it a potential candidate for adjuvant therapy.

[cesanon]

Are there any clinical trials of Milk thistle on human beings (as opposed to mice or Petri dishes)?

What is the mechanism of interference that it has with prescription drugs. You definitely want you doc to be aware of that as he is prescribing other drugs.

When something interferes with one drug, it typically interferes with multiple unrelated drugs.

[kainasar in reply to cesanon]

from Memorial Sloan Kettering Cancer Center’s Integrative Medicine Service, provides evidence-based information

Herb - Drug Interactions

* Cytochrome P450 3A4 substrates: Milk thistle inhibits cytochrome P450 3A4 (4) and can affect the intracellular concentration of drugs metabolized by this enzyme. However, conflicting data indicate no such effects (13)(14)(38). In another study, consumption of milk thistle did not reduce levels of indinavir, an AIDS drug (15).

* UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrates: Milk thistle modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (26).

* Sirolimus: Milk thistle may decrease clearance. Monitor therapy especially when combined with nivolumab, which may interfere with the potential to help prevent rejection of donor kidney in transplant patients (44)(45).

* Haloperidol or Risperidone: 7 cases of pancreatitis were reported following concomitant use of milk thistle (49)

* Aripiprazole: A case of hepatotoxicity was reported with combined use of milk thistle (49).

References

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3. Elyasi S, Hosseini S, Niazi Moghadam MR et al. Aledavood SA, Karimi G. Effect of Oral Silymarin Administration on Prevention of Radiotherapy Induced Mucositis: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. Phytother Res. 2016 Nov;30(11):1879-1885. doi: 10.1002/ptr.5704.

4. Venkataramanan R, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucoronosyl transferase in human hepatocyte cultures. Drug Metab Dispos. 2000;28:1270-3.

5. Adverse Drug Reactions Advisory Committee. An adverse reaction to the herbal medication milk thistle (Silybum marianum). Med J Aust. 1999;170:218-9.

6. Elyasi S, Shojaee FSR, Allahyari A, et al. Topical Silymarin Administration for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. Phytother Res. 2017 Sep;31(9):1323-1329. doi: 10.1002/ptr.5857.

7. Kohno H, et al. Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer. 2002;101:461-8.

8. Tyagi A, et al. Antiproliferative and apoptotic effects of silibinin in rat prostate cancer cells. Prostate 2002 ;53:211-217.

9. Feher J, et al. Liver-protective action of silymarin therapy in chronic alcoholic liver diseases. Orv Hetil. 1989;130:2723-7.

10. Brandon-Warner E, Eheim AL, Foureau DM, et al. Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice. Cancer Lett. Dec 29 2012;326(1):88-95.

11. Ferenci P, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol.1989;1:105-13.

12. Thelen P, Wuttke W, Jarry H, Grzmil M, Ringert RH. Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells. J Urol. 2004 May;171(5):1934-8.

13. Gurley B, Hubbard MA, Williams KD, et al. Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin. J Clin Pharmacol. 2006 ;46(2):201-13.

14. Fuhr U, Beckmann-Knopp S, Jetter A, et al. The effect of silymarin on oral nifedipine pharmacokinetics. Planta Med. 2007;73(14):1429-35.

15. Mills E, Wilson K, Clarke M, et al. Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis. Eur J Clin Pharmacol. 2005;61(1):1-7.

16. Ramasamy K and Agarwal R. Multitargeted therapy of cancer by silymarin. Cancer Lett. 2008 Oct 8;269(2):352-62.

17. Verschoyle RD, Greaves P, Patel K, et al. Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse models of prostate and intestinal carcinogenesis: relationship with silibinin levels. Eur J Cancer. 2008 ;44(6):898-906.

18. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res. 2006;20(12):1036-9.

19. Saller R, Brignoli R, Melzer J, Meier R. An updated systematic review with meta-analysis for the clinical evidence of silymarin.Forsch Komplementmed 2008;15(1):9-20.

20. Ladas EJ, Kroll DJ, Oberlies NH, et al. A Randomized, Controlled, Double-Blind, Pilot Study of Milk Thistle for the Treatment of Hepatotoxicity in Childhood Acute Lymphoblastic Leukemia (ALL).Cancer. 2010;116(2):506-13.

21. Payer BA, Reiberger T, Rutter K, et al. Successful HCV eradication and inhibition of HIV replication by intravenous silibinin in an HIV-HCV coinfected patient. J Clin Virol. 2010 Oct;49(2):131-3.

22. Shakeel M, Trinidade A, McCluney N, Clive B. Complementary and alternative medicine in epistaxis: a point worth considering during the patient’s history. Eur J Emerg Med. 2010 Feb;17(1):17-9.

23. Murata N, Murakami K, Ozawa Y, et al. Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer’s disease mouse model. Biosci Biotechnol Biochem. 2010 Nov 23;74(11):2299-306.

24. Yin F, Liu J, Ji X, et al. Silibinin: A novel inhibitor of Aβ aggregation. Neurochem Int. 2011 Feb;58(3):399-403.

25. Flaig TW, Gustafson DL, Su LJ, et al. A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs. 2007 Apr;25(2):139-46.

26. Mohamed ME, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med. 2011 Mar;77(4):311-21.

27. El-Shitany NA, Hegazy S, El-Desoky K. Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats. Phytomedicine. 2010 Feb;17(2):116-25.

28. Ninsontia C, Pongjit K, Chaotham C, Chanvorachote P. Silymarin selectively protects human renal cells from cisplatin-induced cell death. Pharm Biol. 2011 Oct;49(10):1082-90.

29. Ramakrishnan G, Jagan S, Kamaraj S, Anandakumar P, Devaki T. Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteinases-2 and 9 in rat liver carcinogenesis. Invest New Drugs. 2009 Jun;27(3):233-40.

30. Murata N, Murakami K, Ozawa Y, et al. Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer’s disease mouse model. Biosci Biotechnol Biochem. 2010;74(11):2299-306.

31. Bannwart CF, Peraçoli JC, Nakaira-Takahagi E, Peraçoli MT. Inhibitory effect of silibinin on tumour necrosis factor-alpha and hydrogen peroxide production by human monocytes. Nat Prod Res. 2010 Nov;24(18):1747-57.

32. Li Volti G, Salomone S, Sorrenti V, et al. Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice. Cardiovasc Diabetol. 2011 Jul 14;10:62.

33. Kim S, Han J, Kim JS, et al. Silibinin suppresses EGFR ligand-induced CD44 expression through inhibition of EGFR activity in breast cancer cells. Anticancer Res. 2011 Nov;31(11):3767-73.

34. Blaising J, Lévy PL, Gondeau C, et al. Silibinin inhibits hepatitis C virus entry into hepatocytes by hindering clathrin-dependent trafficking. Cell Microbiol. Cell Microbiol. 2013 Nov;15(11):1866-82.

35. Mooiman KD, Maas-Bakker RF, Moret EE, et al. Milk Thistle’s Active Components Silybin and Isosilybin: Novel Inhibitors of PXR-mediated CYP3A4 Induction. Drug Metab Dispos. 2013 Aug;41(8):1494-504.

36. Zhang S, Yang Y, Liang Z, et al. Silybin-mediated inhibition of notch signaling exerts antitumor activity in human hepatocellular carcinoma cells. PLoS One. 2013 Dec 27;8(12):e83699.

37. Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future. Phytother Res. 2010 Oct;24(10):1423-32.

38. Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The Effects of Milk Thistle (Silybum marianum) on Human Cytochrome P450 Activity. Drug Metab Dispos. 2014 Oct;42(10):1611-6.

39. Wah Kheong C, Nik Mustapha NR, Mahadeva S. A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. Dec 2017;15(12):1940-1949.e1948.

40. Ebrahimpour-Koujan S, Gargari BP, Mobasseri M, et al. Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A Triple-blinded randomized controlled clinical trial. Phytomedicine. May 15 2018;44:39-44.

41. Seeff LB, Curto TM, Szabo G, et al. Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. Hepatology. Feb 2008;47(2):605-612.

42. Fried MW, Navarro VJ, Afdhal N, et al. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA. Jul 18 2012;308(3):274-282.

43. Freedman ND, Curto TM, Morishima C, et al. Silymarin use and liver disease progression in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial. Aliment Pharmacol Ther. Jan 2011;33(1):127-137.

44. Jiao Z, Shi XJ, Li ZD, et al. Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients. Br J Clin Pharmacol. Jul 2009;68(1):47-60.

45. Barnett R, Barta VS, Jhaveri KD. Preserved Renal-Allograft Function and the PD-1 Pathway Inhibitor Nivolumab. N Engl J Med. Jan 12 2017;376(2):191-192.

46. Grant JE, Redden SA, Chamberlain SR. Milk Thistle Treatment for Children and Adults with Trichotillomania: A Double-Blind, Placebo-Controlled, Crossover Negative Study. J Clin Psychopharmacol. 2019 Mar/Apr;39(2):129-134.

47. Karbasforooshan H, Hosseini S, Elyasi S, Fani Pakdel A, Karimi G. Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2019 Feb;33(2):379-386.

48. Dupuis ML, Conti F, Maselli A, et al. The Natural Agonist of Estrogen Receptor β Silibinin Plays an Immunosuppressive Role Representing a Potential Therapeutic Tool in Rheumatoid Arthritis. Front Immunol. 2018 Aug 17;9:1903.

49. Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018 Dec 29;52(6):983-996.

[kainasar in reply to cesanon]

also, using references above

Silibinin, one of the flavonoids, demonstrated antioxidant and anti-inflammatory effects by inhibiting release of hydrogen peroxide and production of tumor necrosis factor alpha (31). Another study showed improvement in endothelial dysfunction via reduction in circulating and vascular asymmetric dimethylarginine (ADMA) levels. ADMA is an endogenous inhibitor of nitric oxide synthase (NOS) and is believed to play a role in endothelial dysfunction, associated with cardiovascular disease (32). Silibinin also inhibits the early phase of hepatitis C viral infection by affecting endosomal trafficking of virions (34).

Other studies indicate milk thistle flavonoids exert anticancer effects by arresting G1 and S phases of the cell cycle (8). Silybin inhibited hepatocellular carcinoma cell growth via the Notch signaling pathway (36). Silibinin suppressed the epidermal growth factor receptor (EGFR)-induced expression of CD44, the transmembrane receptor for hyaluronan implicated in tumor cell invasion and metastasis by inhibiting EGFR activity in breast cancer cells (33). Suggested mechanisms for reduced efficacy of silibinin in liver tumor-bearing animals that were co-administered ethanol include impaired hepatic processing of silibinin (10).

Silybin and isosilybin were shown to strongly inhibit PXR-mediated CYP3A4 induction (35)

High doses of silibinin can elevate bilirubin and liver enzymes (25).

Hope this helps.

[j-o-h-n]

Give a little Thistle:

youtube.com/watch?v=wSY8qOO...(Not working as expected?)

Oops....

Good Luck and Good Health.

j-o-h-n Monday 08/13/2018 5:10 PM EDT

[Mormon1]

it may contraindicate certain c meds check with pharacist and c doc