St. John's Wort

Note: This review is focused only on aspects of St. John’s wort that may be of greatest interest to individuals with cancer. Please seek additional information sources for a more comprehensive review of St. John’s wort as it relates to other health conditions and diseases.

Overview & Background

St. John’s wort is one of the most commonly used herbs in the United States today. People take this herb for a variety of reasons. Some popular reasons for using St. John’s wort include:

• Treatment and management of mild to moderate depression.
• Treatment and management of seasonal affective disorder (SAD), a type of depression associated with certain seasons of the year.
• To manage anxiety.
• To treat or manage cancer, HIV/AIDS, and hepatitis C, most often in conjunction with conventional medical approaches such as medication, surgery, chemotherapy, and/or radiation therapy (research does not support St. John's wort alone as an effective treatment for these conditions).
• To treat nerve pain (neuropathy/neuralgia due to diabetes and neuropathy of other causes).
• To help people quit smoking.
• To manage symptoms of menopause.

There are many other proposed uses for St. John’s wort, but these are some of the more common reasons for which people may try this herb.

Effectiveness

Depression and Anxiety

St. John’s wort has been studied most extensively for treating mild to moderate depression. Research on this topic is mixed. Some research supports that St. John’s wort is effective for treating mild to moderate depression, but some studies do not demonstrate that St. John’s wort is an effective anti-depressant.

There are a number of reasons for why the research is unclear and conflicting in this area.

• Hypericum perforatum is the species of St. John’s wort that is most commonly used in over-the-counter herbal preparations. This plant is one of 450 species of related plants. Herbal supplements are unregulated and it is possible that different species of plants in different products will give conflicting results.
• The dosages and active ingredients in over-the-counter St. John’s wort products are not always standardized. It is difficult to know if all research studies are using equivalent products.
• Various parts of the St. John’s wort plant may contain different active components. Herbal products that are formulated from different plant parts may have different actions in the body.
• The time of year and location from which St. John’s wort is harvested may affect the active ingredients in the plants
• Some herbal products are formulated from “wild crafted” St. John’s wort, while others are made from cultivated or farmed St. John’s wort. This may affect active plant components as well.

For all of these reasons, we cannot know with certainty that St. John’s wort is as effective as other medications for treating and managing mild to moderate depression. Nevertheless, there is reasonable evidence that St. John’s wort is more effective than placebo (no treatment) and as effective as certain types of antidepressants known as SSRIs (selective serotonin reuptake inhibitors) for treating mild to moderate depression. St. John’s Wort may not be effective for treating more severe depression.

Cancer

Cell and animal studies suggest that St. John’s wort may provide benefit to people undergoing cancer treatment. Well controlled human studies are not yet published, but clinical trials have been conducted. Published results from these trials should become available within the next few years. Generally, this research has focused using St. John’s wort to manage or alleviate some of the side effects of cancer and its treatment including menopause, fatigue, and depression.

Beyond the potential anti-cancer benefits or symptom management applications for St. John’s wort, cell and animal studies have demonstrated that St. John’s wort may be useful as part of a type of cancer treatment called photodynamic therapy. St. John’s wort can make cancer (and other) cells more sensitive to light therapies and in this way provide benefit to patients undergoing this type of treatment. It is likely that future studies in humans will further clarify the benefits and risks of using St. John’s wort as part of photodynamic therapy.

Finally, cell and animal studies have suggested that St. John’s wort may have the most significant anti-cancer activity against hematologic cancers, such as leukemia. Human studies of hematologic cancers will be required to determine if these same benefits can be realized in people.

Other Uses

The use of St. John’s wort to treat or manage other diseases and conditions is not well-studied. There are no well-controlled human trials to support that St. John’s wort is effective for managing seasonal affective disorder (SAD), anxiety, neuropathy, HIV/AIDS, or hepatitis C. This does not mean it is proven that St. John’s wort will not be helpful in these circumstances, just that we simply do not have enough information to draw well-supported conclusions in these cases.

Neuropathy

Neuropathy (nerve pain, numbness, and tingling) is of particular interest to individuals being treated for cancer because some of the medications used in cancer treatment can cause neuropathy. Unfortunately, there is no research to support that St. John’s wort will prevent or treat neuropathy.

Of more concern is one case report suggesting that St. John’s wort may cause neuropathy in certain situations. For this reason, St. John’s wort should not be used for treatment of cancer treatment-related neuropathy.

Smoking Cessation

There are two small published studies on the use of St. John’s wort to help with smoking cessation. These studies suggest that St. John’s wort may improve the likelihood of success for people who are trying to quit smoking.  A double-blinded, placebo-controlled clinical trial to investigate the benefits of St. John’s wort for smoking cessation is on-going. When results of this trial become available, they should help to clarify whether St. John’s wort is of benefit to individuals who are trying to quit smoking.

Symptoms of Menopause

It is difficult to know with certainty whether St. John’s wort can alleviate symptoms of menopause such as hot flashes and insomnia. To date, the research that has been conducted on this topic has used a combination of St. John’s wort and black cohosh, so it is not possible to know which herb or whether it is truly the combination of these two herbs that may alleviate symptoms of menopause. A clinical trial examining benefits of St. John’s wort alone for alleviating hot flashes in postmenopausal women with a history of non-metastatic breast cancer.

Contraindications & Cautions for St. John’s Wort

St. John’s is considered safe for use ranging from 8 weeks to one year. However, the use of St. John’s wort by people who are being treated for cancer should be avoided. Numerous studies have demonstrated that St. John’s wort can interact with many medications, including several that are commonly used in cancer treatment.

Some oncologists and health experts believe that interactions between chemotherapeutic cancer medications and herbs such as St. John’s wort are responsible for many of the unexpected toxicities seen in the cancer clinic. As well, many oncologists are concerned about possible undertreatment of some cancer patients that may occur when herbs such as St. John’s wort cause decreased levels of cancer medications in the body.

St. John’s wort may interact negatively with any of the following cancer treatment-related medications:

• Irinotecan (Camptosar®) or Topotecan (Hycamptin®)
• Imatinib (Gleevec®)
• Warfarin (Coumadin®)
• Any Immunosuppressant Medication including cyclosporine (Sandimmune®, Neoral®, Gengraf®), azathioprine (Azasan®, Imuran®), daclizumab (Zenapax®), mycophenolate (CellCept®), tacrolimus (Prograf®), basiliximab (Simulect®), sirolimus (Rapamune®), muromonab-CD3 (OKT3®, Orthoclone®), and prednisone (Prednisone Intensol®, Sterapred®, Sterapred DS®, Deltasone®, Orasone®)
• Tamoxifen (Nolvadex®)
• Odansetron (Zofran®)
• Taxanes (Taxotere® and Taxol®)
• Vinca Alkaloids (Vinblastine [Velban®], Vincristine [Oncovin®], Vindesine [Eldisine®], and Vinorelbine[Navelbine®])
• Etoposide (VP-16®, Etopophos®, Vepesid®, Eposin®)
• Corticosteroids such as prednisone (Intensol®, Sterapred®, Sterapred® DS, and Deltasone®)
• Phenytoin (Dilantin®)
• Procarbazine (Matulane®)
• Any medication that is used to treat depression or mood disorders such as paroxetine (Paxil®), and sertraline (Zoloft®), amitriptyline (Elavil®), and others.

For all of these reasons, St. John’s wort should not be used by people who are receiving cancer chemotherapy medications. If you are using St. John’s wort to manage another medical condition such as depression, do not suddenly or abruptly stop using this herb without talking to your doctor first. You may have serious side effects if you stop using this herb all at once.

As well, it is important to keep in mind that depression is a serious medical condition. Do not try to manage this on your own. You should work with your oncologist and your mental health care provider to find the best, safest way to manage depression during and after your cancer treatment.

One additional concern with St. John’s wort is the quality of the product. Independent researchers have confirmed that some St. John’s wort products do not contain the ingredients as claimed on the product label. As well, some products have been found to be contaminated with cadmium and other heavy metals. For more information on how to choose a good quality dietary supplement, please see the American Cancer Society's information  Dietary Supplements: How To Know What Is Safe.

Disclaimer

This list of contraindications is not guaranteed to be complete and is based upon currently available evidence, which is subject to change as new research emerges. There are many other medications that may interact negatively with St. John’s wort. This list addresses medications commonly used to treat individuals with cancer and does not address all possible medication interactions. Always discuss your use of dietary supplements with your doctor. Be sure to let your doctor know about any dietary supplements or other over-the-counter medications that you currently use or plan to use during your cancer care.

References

1. Saw CL, Heng PW, Olivo M. Potentiation of the photodynamic action of hypericin. J Environ Pathol Toxicol Oncol. 2008;27(1):23-33.
2. Hellum BH, Nilsen OG. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol. 2008;102(5):466-75.
3. Wessels JT, Busse AC, Rave-Fränk M, Zänker S, Hermann R, Grabbe E, Müller GA. Photosensitizing and radiosensitizing effects of hypericin on human renal carcinoma cells in vitro. Photochem Photobiol. 2008;84(1):228-35.
4. Clinicaltrials.gov. Hypericum Perforatum (St. John's Wort) in Relieving Hot Flashes in Postmenopausal Women With Non-Metastatic Breast Cancer. Clinical Trials Identifier NCT00110136. Available at: http://www.clinicaltrials.gov/. Accessed Feb 1, 2008.
5. Clinicaltrials.gov. Sertraline Compared With Hypericum Perforatum (St. John's Wort) in Treating Mild to Moderate Depression in Patients With Cancer. Clinical Trials Identifier NCT00066859. Available at: http://www.clinicaltrials.gov/. Accessed Feb 1, 2008.
6. Clinicaltrials.gov. St. John's Wort in Relieving Fatigue in Patients Undergoing Chemotherapy or Hormone Therapy for Cancer. Clinical Trials Identifier NCT00005805. Available at: http://www.clinicaltrials.gov/. Accessed Feb 1, 2008.
7. Clinicaltrials.gov. St. John's Wort for Tobacco Cessation. Clinical Trials Identifier NCT00405912. Available at: http://www.clinicaltrials.gov/. Accessed Feb 1, 2008.
8. National Center for Complementary and Alternative Medicine. Herbs at a Glance: St. John’s Wort. Available at: http://nccam.nih.gov/health/stjohnswort/index.htm. Accessed Feb 1, 2008.
9. National Center for Complementary and Alternative Medicine. Get the Facts: St. John’s Wort and Depression. Available at: http://nccam.nih.gov/health/stjohnswort/sjwataglance.htm. Accessed Feb 1, 2008.
10. Natural Medicines Comprehensive Database. St. John’s Wort. Full Monograph. Available at: http://www.naturaldatabase.com. Accessed February 1, 2008.
11. Hu ZP, Yang XX, Chen X, Cao J, Chan E, Duan W, Huang M, Yu XQ, Wen JY, Zhou SF. A mechanistic study on altered pharmacokinetics of irinotecan by St. John's wort. Curr Drug Metab. 2007;8(2):157-71.
12. Bhuvaneswari R, Yuen GY, Chee SK, Olivo M. Hypericin-mediated photodynamic therapy in combination with Avastin (bevacizumab) improves tumor response by downregulating angiogenic proteins. Photochem Photobiol Sci. 2007;6(12):1275-83.
13. Hellum BH, Nilsen OG. The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol. Basic Clin Pharmacol Toxicol. 2007;101(5):350-8.
14. Kleban J, Mikes J, Szilárdiová B, Koval J, Sacková V, Solár P, Horváth V, Hofmanová J, Kozubík A, Fedorocko P. Modulation of hypericin photodynamic therapy by pretreatment with 12 various inhibitors of arachidonic acid metabolism in colon adenocarcinoma HT-29 cells. Photochem Photobiol. 2007;83(5):1174-85.
15. Bhuvaneswari R, Gan YY, Yee KK, Soo KC, Olivo M. Effect of hypericin-mediated photodynamic therapy on the expression of vascular endothelial growth factor in human nasopharyngeal carcinoma. Int J Mol Med. 2007;20(4):421-8.
16. Marchetti S, Mazzanti R, Beijnen JH, Schellens JH. Concise review: Clinical relevance of drug drug and herb drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein). Oncologist. 2007;12(8):927-41.
17. Quiney C, Billard C, Faussat AM, Salanoubat C, Kolb JP. Hyperforin inhibits P-gp and BCRP activities in chronic lymphocytic leukaemia cells and myeloid cells. Leuk Lymphoma. 2007;48(8):1587-99.
18. Ritz R, Wein HT, Dietz K, Schenk M, Roser F, Tatagiba M, Strauss WS. Photodynamic therapy of malignant glioma with hypericin: comprehensive in vitro study in human glioblastoma cell lines. Int J Oncol. 2007;30(3):659-67.
19. Meijerman I, Beijnen JH, Schellens JH. Herb-drug interactions in oncology: focus on mechanisms of induction. Oncologist. 2006;11(7):742-52.
20. Kiesslich T, Krammer B, Plaetzer K. Cellular mechanisms and prospective applications of hypericin in photodynamic therapy. Curr Med Chem. 2006;13(18):2189-204.
21. Lawvere S, Mahoney MC, Cummings KM, Kepner JL, Hyland A, Lawrence DD, Murphy JM. A Phase II study of St. John's Wort for smoking cessation. Complement Ther Med. 2006;14(3):175-84.
22. Quiney C, Billard C, Salanoubat C, Fourneron JD, Kolb JP. Hyperforin, a new lead compound against the progression of cancer and leukemia? Leukemia. 2006;20(9):1519-25.
23. Barnes J, Barber N, Wheatley D, Williamson EM. A pilot randomised, open, uncontrolled, clinical study of two dosages of St John's wort (Hypericum perforatum) herb extract (LI-160) as an aid to motivational/behavioural support in smoking cessation. Planta Med. 2006;72(4):378-82.
24. Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin HH. Black cohosh with or without St. John's wort for symptom-specific climacteric treatment--results of a large-scale, controlled, observational study. Maturitas. 2007;57(4):405-14.
25. Chung DJ, Kim HY, Park KH, Jeong KA, Lee SK, Lee YI, Hur SE, Cho MS, Lee BS, Bai SW, Kim CM, Cho SH, Hwang JY, Park JH. Black cohosh and St. John's wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J. 2007;48(2):289-94.
26. Uebelhack R, Blohmer JU, Graubaum HJ, Busch R, Gruenwald J, Wernecke KD. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol. 2006;107(2 Pt 1):247-55.

Publish Date: February 2008