If you have oestrogen receptor-positive (ER+) breast cancer, it is likely that you are on tamoxifen. But, did you know that the effectiveness of this drug can be boosted or compromised based on everyday foods and drinks?
How does tamoxifen work?
Tamoxifen is one of the widely prescribed breast cancer treatments for premenopausal women. It works by blocking oestrogen receptors in breast cancer cells, preventing oestrogen from activating the cancer cells to grow further.
For tamoxifen to work, your body needs to process it to turn it into its active form, endoxifen. At each step in the process, a specific liver enzyme – a protein that speeds up a process within cells – is used to convert one form of the drug into another, until endoxifen is formed (see diagram). The main enzyme involved in the conversion of tamoxifen to endoxifen is called CYP2D6.
In order to make sure that tamoxifen is converted into its active form (endoxifen), all the liver’s CYP2D6 enzyme should be utilised. However, this enzyme is also needed to break down other substances. Therefore, these substances can “occupy” this CYP2D6, leaving it less available to convert tamoxifen into endoxifen. This would essentially result in the tamoxifen you took as being labelled ineffective as the body would not be able to process it1.
Did you know that you can track your side effects, including those most commonly caused by tamoxifen, such as hot flushes, nausea and weight gain, with OWise? Being able to visualise how your symptoms change over time can help you improve communication with your care team and make sure you receive the best care possible. Download the free app today.
Certain foods, drinks and medications can interfere with the conversion of tamoxifen to endoxifen by the CYP2D6 enzyme to different extents. If this process is altered, the effectiveness of tamoxifen in your body can also change. Although this enzyme is very important in this process, other enzymes such as CYP3A4/5 are also involved (see the diagram).
Is there anything that I should avoid eating or drinking while on Tamoxifen?
Grapefruit and grapefruit juice are well-known disruptors of numerous medications 2. This is mainly due to chemicals called “furanocoumarins” present in grapefruit. They bind with the enzyme CYP3A4 3, which means that drugs such as tamoxifen cannot use the engaged CYP3A4 enzymes to convert into their active forms in the body, reducing the drug’s effectiveness. In some cases, just one grapefruit or one glass of grapefruit juice is enough to limit the effectiveness of CYP3A4 2. Seville oranges (often used in marmalade) also produce furanocoumarins 3, 4, so you may want to limit your intake of these as well.
“I would strongly discourage patients on tamoxifen to have grapefruit juice. Research has shown that the enzyme that components of grapefruit juice block [CYP3A4] is very important for the production of endoxifen and can reduce the effect of the tamoxifen treatment as a whole.”
Curcumin, the bright orange-yellow substance in turmeric, is a popular spice to ingest, especially in those undergoing cancer treatments, due to its supposed anti-cancer effects 5,6. Due to its poor absorption and rapid metabolism in the body, curcumin is often ingested in combination with black pepper, as it contains piperine, which increases the effectiveness of curcumin in the body by about 20 fold 7.
Previous studies have found mixed results when it comes to whether curcumin would increase or decrease the effectiveness of tamoxifen 8,9,10. However, a recent breakthrough found an overall negative relationship between tamoxifen and curcumin 11. The study found that with curcumin consumption, the amount of active endoxifen circulating the body decreased. This amount further decreased with the additional consumption of piperine. Therefore, if you are on tamoxifen it may be best to avoid turmeric and curcumin (particularly in concentrated supplement form), as it can lower the concentration of endoxifen in the body such that it interferes with the therapeutic impact of the drug.
You may have heard of black cohosh as being a herbal alternative to counteract menopausal symptoms such as hot flushes. Although some people may find it helpful, there is a lack of evidence supporting the efficacy of black cohosh for reduction of hot flushes 12, and according to the NICE guidelines, the herb is “not recommended for the treatment of menopausal symptoms in women with breast cancer.”
Lab research has shown that black cohosh can inhibit the two core enzymes that convert tamoxifen to endoxifen, meaning it may reduce the function of tamoxifen. As this research studies human interactions in a very basic form, more clinical research is needed to actually show whether the effect in the body is significant. It may be best to avoid black cohosh if you are taking Tamoxifen, and speak to your doctor about alternatives to counteract your hot flushes and other menopausal symptoms. You can also head to our previous instagram post for tips on how to manage them.
St. John’s Wort
St. John’s Wort is a herb that is often used to treat depression, anxiety, hot flashes and sleep issues. It is particularly popular amongst cancer patients, as it is often seen as a safe natural remedy13 14. However, due to some of its properties, St. John’s Wort may interact with cancer medications and cause them to be less effective. It has been found that St. John’s Wort acts as an inducer of CYP enzymes, and in particular of the enzyme CYP3A4. In other words, substances within St. John’s Wort can lead to more CYP enzymes and increase their activity15, 16, 17, 18, 19.
St. John’s Wort and CYP enzyme interactions
As discussed previously, CYP enzymes are key in breaking down tamoxifen into its active form endoxifen. Increasing the number of these enzymes may lead to tamoxifen being cleared out of your body too quickly, before it can have the desired effect on blocking the cancer cell growth. Clinical trials have shown that St. John’s Wort interacts with the chemotherapy drugs irinotecan 20, imatinib 21 and docetaxel 22 by reducing the amount of medication circulating in the blood. This was due to the increased CYP3A4 enzymes which cause the chemo-drugs to be removed too quickly23.
It may be best to avoid St. John’s Wort supplements if you are on tamoxifen or discuss this with your doctor. It is notable, for example, that a clinical trial investigating the use of St. John’s Wort to relieve hot flashes in breast cancer patients has been stopped due to “concerns about interaction between St. John’s Wort and tamoxifen”24.
Did you know there is more than one type of ginseng? Two common ones are American ginseng (the scientific name is Panax quinquefolius), and Asian ginseng (the scientific name is Panax ginseng). Most studies are focused on Asian ginseng, and for this blog we refer mainly to Asian ginseng.
Ginseng is a strong inhibitor of the enzymes CYP3A4 and CYP2D6 19, 27, 28. This means that it stops these enzymes from working, and may affect your body’s ability to process certain drugs which require the use of these enzymes. In one case, the use of ginseng alongside imatinib (a chemotherapy drug) led to liver damage which researchers linked to interactions between ginseng and imatinib 29. Due to ginseng’s known inhibition of important CYP enzymes, it is perhaps best to avoid high levels of this supplement whilst taking tamoxifen.
Is there anything that I should eat or drink in moderation while on Tamoxifen?
Some foods are recommended to be taken in moderation while you are on tamoxifen as some studies have shown a link between them and the metabolism of this treatment. However, their effects are small so having these foods once in a while is okay.
Chamomile tea is a soothing drink enjoyed daily by many and has seemingly countless benefits. However, studies have found that in lab experiments, chamomile has the ability to interact and inhibit CYP2D6 and CYP3A4 enzymes 30. This means that theoretically, chamomile could interfere with the conversion of tamoxifen into its active endoxifen form in the body. But there is currently no clinical evidence to show this – there is no doubt that more research on this link needs to be carried out, especially with clinical studies that directly look into whether chamomile could affect the effectiveness of tamoxifen in the body. For now, it is best to enquire with your doctor or nutritionist for guidance on whether to start or continue ingesting chamomile whilst taking tamoxifen.
Consuming soya remains controversial amongst those diagnosed with breast cancer. The concern often stems from the fact that soya contains what is known as “phytoestrogens” – chemicals which have structures similar to oestrogen. Because of the potential for these chemicals to bind to oestrogen receptors, it was hypothesised that they could potentially stimulate the growth of ER+ breast cancers 31, 32.
However, there is actually increasing evidence to suggest that soy consumption may be beneficial in reducing breast cancer risk, mortality and recurrence 31, 33, 34, even whilst on tamoxifen 35. Currently, there are no definitive answers to whether soy should or shouldn’t be included in the diet. With more human clinical studies, our understanding can develop.
There is no clear evidence to suggest that you should stop consuming soya after being diagnosed with breast cancer and whilst taking tamoxifen – it may even be beneficial. So, if you do regularly have soya, or cut it out because you thought it could affect your treatment, feel free to carry on consuming it as part of a well-balanced diet. If you don’t like soya or never included it in your diet before, there’s no need to start now, but if you would like to include it, talk to your doctor or nutritionist who can advise you further.
To learn more about Tamoxifen side effects and how to deal with them, head to our previous blog.
Like soya, flaxseeds also contain phytoestrogens, which have caused concern for women with breast cancer over the years. However, current evidence seems to suggest that flaxseeds are safe for people who are on tamoxifen. Not only are they safe, but also like soya, flaxseeds may, in fact, be beneficial to those with breast cancer and who are on tamoxifen, with studies suggesting that its consumption may reduce the risk, growth and recurrence of breast cancer 36, 37, 38,39, 40.
Tangerines and other citrus peels contain a chemical called tangeretin, which has been shown to reduce the effectiveness of tamoxifen 41. However, the actual flesh of the fruit contains a lot less tangeretin than the peel, so eating moderate amounts of tangerines and other such citrus fruits should be okay. You may want to be more careful with the amount of marmalades you consume, however, as these tend to include the peel.
Is there anything that I can eat or drink to boost the effectiveness of tamoxifen?
Green tea is a relaxing and comforting drink that pops up time and time again in health forums, with seemingly countless benefits. And it doesn’t stop there – studies have shown that green tea interacts together with tamoxifen, boosting its effectiveness 42,43. The mechanism leading to the beneficial interaction is thought to involve flavonoids (substances with a chemical structure called “phenolic”) such as EGCG (Epigallocatechin gallate) present in green tea.
Interestingly, these green tea flavonoids have even been reported to reverse the mechanisms by which cancer cells could manage to escape from tamoxifen and become resistant to it 44, 45, 46. Therefore, co-administration of green tea with tamoxifen could also be useful in tamoxifen-resistant breast cancer cases 47.
Which medications should I be aware of on Tamoxifen?
Antidepressive agents are often prescribed to women with breast cancer, not only to target depression but also for anxiety and hot flushes 48. However many antidepressants inhibit CYP2D6 to various extents, which can interfere with the conversion of tamoxifen to endoxifen 49, 50,51 (see diagram). In particular, the antidepressants fluoxetine (Prozac® and Sarafem®) and paroxetine have the ability to greatly reduce the effectiveness of tamoxifen as they are strong inhibitors of CYP2D6, therefore they should not be prescribed in conjunction with tamoxifen.
Safer antidepressants to take when on Tamoxifen
However, there are safer alternative antidepressants to take whilst on Tamoxifen that do not inhibit CYP2D6, such as escitalopram, venlafaxine and mirtazapine 52. Escitalopram (Cipralex® or Lexapro®) is the preferred prescribed antidepressant to breast cancer patients who are on tamoxifen, as it interacts less in the conversion of tamoxifen into endoxifen compared to other antidepressants such as fluoxetine 53. If you are on tamoxifen and taking prescribed antidepressants, you will likely be taking one of these three options. If your antidepressant is not one of the three, it may be worth having a conversation with your oncologist at your next appointment to enquire whether the antidepressant you are on is the best option for you and why.
Several antipsychotic medications have also been shown to be inhibitors of CYP2D6 51, 54, 55, 56. In particular of the common antipsychotics, thioridazine, perphenazine and pimozide are the strongest CYP2D6 inhibitors and therefore should not be prescribed alongside tamoxifen. Chlorpromazine, fluphenazine and aloperidol are also CYP2D6 inhibitors, but to a lesser extent. If you have been prescribed any of the antipsychotics mentioned and you are on tamoxifen, you may want to speak to your doctor about whether the antipsychotic you are on is the best option for you – there are several alternatives that are safer to take on tamoxifen that you may want to discuss with them.
Did you know that the British National Formulary is published and updated regularly by NICE? It is a great resource to check for drug interactions, you can search according to the drug name and it provides you with information about known interactions and side effects.
The medication warfarin is used as a blood thinner. Warfarin and Tamoxifen are known to interact with each other, leading to an increased risk of bleeding57. The exact mechanism of this interaction is unknown, but there have been several cases of bleeding complications in people who are taking both warfarin and Tamoxifen58. As a result of this evidence, the BNF (British National Formulary) has listed warfarin and Tamoxifen as having a severe interaction due to the increased risk of bleeding59. If these medications are prescribed to the same person, close and constant monitoring is recommended.
The important takeaways
It’s important to note here that most foods and drinks are perfectly fine to have, especially in moderation, and some are even beneficial to ingest whilst on tamoxifen. However, remember that too much of a good thing can sometimes have negative effects so always be careful with taking concentrated supplements and speak to your doctor or cancer nutritionist about your diet before introducing something new or making any drastic changes.
Since most foods are okay in moderation it may be helpful to make notes of what you have eaten on a daily basis – you can do this right in the OWise app! This way, you can keep track of how often you are eating certain foods or drinking certain drinks so that you can plan when to cut back on something you have been having too often, or know when to treat yourself to something you don’t often have.
If you want to learn more about how tamoxifen works, see our previous blog.
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