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Milk Thistle active Silymarin decreases Doxorubicin-induced Cardiotoxicity in Children with leukemia

Feb 7, 2020

Highlights

The bioactive Silymarin from the herb Milk Thistle is an antioxidant and has been shown to have certain benefits in cancer patients such as cardio-protective effects through reducing oxidative stress. Use of Milk Thistle active Silymarin along with Doxorubicin benefits children with leukemia by reducing the Doxorubicin-induced cardiotoxicity as demonstrated in a clinical study with children with acute lymphoblastic leukemia.



Doxorubicin Chemotherapy & Cardiotoxicity in Leukemia

Doxorubicin is a chemotherapy drug that has been approved for use as standard of care treatment in many cancer indications including acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), neuroblastoma, sarcomas, breast, ovarian, bladder, thyroid, gastric and many other cancers. Doxorubicin is able to kill the abnormally fast growing cancer cells by causing excessive DNA damage and increasing oxidative stress that also induces cell death. However, this impact of Doxorubicin also results in severe collateral damage to the healthy cells, with cardiotoxicity as one of the most severe side-effects having a probability of fatal congestive heart failure, that could occur either during treatment or months or years after the therapy. Increased probability of cardiotoxicity, as assessed by various signs and symptoms including decline in heart function or change in levels of key enzyme markers of cardiotoxicity, increases with increasing the total cumulative dose of Doxorubicin.

Milk Thistle active Silymarin & Doxorubicin-induced Cardiotoxicity in Children with leukemia, benefits of silymarin in cancer


This conundrum of eliminating the cancer vs. dealing with severe and sometimes irreversible side-effects is an ongoing dilemma in the cancer community. Hence, there are continuous efforts to find approaches that can help alleviate or protect the patient from the severe side-effects. Researchers have studied the effect of different natural plant derived supplements when taken along with Doxorubicin on the cardiotoxicity endpoints in cancer cells and animal disease models, similar ones as used in the drug development process for approved drugs. One such plant derived active Silymarin from the plant Milk thistle has been tested in many experimental studies and has shown protective effects on the heart.

Milk Thistle and its actives


Milk thistle is a plant that has been used for centuries as a treatment for liver and bile disorders in Europe. It is also available as a dietary supplement. Milk thistle got its name from the milky sap that is released when the leaves are broken. The two major bioactive ingredients of Milk Thistle are:

  • Silymarin
  • Silibinin

Milk Thistle active Silymarin for Doxorubicin-induced Cardiotoxicity in Leukemia

Silymarin has been shown experimentally to have cardioprotective effects when given along with Doxorubicin (reducing Doxorubicin-induced cardiotoxicity). Silymarin is able to reduce oxidative stress, the root cause of cardiotoxicity. It is an antioxidant and able to reduce damage to the membranes and proteins by the reactive species, that are created as part of Doxorubicin mechanism of action, by preventing depletion of the inherent antioxidant machinery of healthy cells (Roskovic A et al, Molecules 2011).

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Clinical Study on Silymarin & Doxorubicin-induced Cardiotoxicity


A clinical study from the Tanta University in Egypt tested the benefits/cardio-protective effects of Silymarin from Milk Thistle in children with acute lymphoblastic leukemia (ALL), who are treated with Doxorubicin (Hagag AA et al, Infect Disord Drug Targets. 2019). In this study on 80 children with ALL, 40 of them were treated with Doxorubicin along with Silymarin at 420 mg/day (Group I – experimental) and the remaining 40 were only treated with Doxorubicin without the Silymarin (Group 2 – placebo). The assessment of cardiac function in these children was done through conventional echo-Doppler measures of heart systolic and diastolic function. They found that in the Silymarin group, there was ‘decreased early Doxorubicin-induced left ventricular systolic function disturbances (cardiotoxicity)’ over the placebo group.

Conclusion

The study indicates that Milk Thistle active Silymarin may have benefits in cancer patients such as decreasing Doxorubicin-induced Cardiotoxicity in Children with leukemia. This clinical study, although with a small number of leukemia children, is providing some confirmation of the cardioprotective effects (benefits) of Milk thistle active Silymarin as seen in experimental disease models. Despite the beneficial impact of natural supplements based on experimental and small clinical studies, cancer patients must use caution in taking these supplements along with their cancer treatments. These natural supplements have not gone through extensive testing and regulatory approval and are not meant to treat, prevent or cure the disease. Also, there are possibilities of plant supplement and drug interactions that can interfere with the treatment and could be dangerous in some cases. Hence, cancer patients should always consult with their doctor before using any natural supplement.


Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer. Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.


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