Is the Antioxidant Melatonin Dangerous during Chemotherapy and Radiation?

Written By: Dr. Adam McLeod, ND, BSc (Hons)

It is not unusual for patients to be intimidated by their medical oncologists to fear all natural therapies. They are told to specifically avoid all antioxidants because they will neutralize the effects of chemotherapy and radiation. This broad generalization that all antioxidants should be avoided is simply not supported by scientific evidence. On an intuitive level, it makes sense that if chemotherapy is creating oxidative damage as its mechanism of action then providing the body with antioxidants would theoretically neutralize this mechanism. There are legitimate concerns with specific chemotherapies and high doses of synthetic antioxidants. However, there are many double blind human trials which demonstrate that antioxidant supplementation at moderate doses decreases side effects without interfering with the effects of the chemotherapy^12,13,14. There is also no debating that patients who consume natural sources of antioxidants respond better to chemotherapy and radiation with less side effects^33,7. If antioxidants are to be feared, then why do patients with better antioxidant capacity in their blood respond better to these conventional therapies?

There are several things which must be considered. First of all this simplistic view that all antioxidants are bad has long been debunked and this is not supported in the scientific literature³¹. Secondly, not all chemotherapies work by creating oxidative damage so the argument against antioxidants in these cases is nonsense. Another important point is that antioxidants can help your healthy cells to recover from the residual toxic effects of chemotherapy^28,29,30. To add to the hypocrisy of the “avoid all antioxidant stance”, it is not unusual for oncologists to administer powerful pharmaceutical antioxidants such as theophylline to reduce side effects from chemotherapy³⁴.

The antioxidant capacity of your blood is a measure of how effectively your blood is capable of neutralizing free radicals. The consumption of antioxidant rich foods dramatically increases the concentration of antioxidants in the blood which consequently increases antioxidant capacity³. It is well known that patients who have lower antioxidant capacity in their blood have greater side effects to chemotherapy³².

The notion that all medical oncologists share this view of fearing antioxidants is simply not true. There are major integrative cancer centres in the US where naturopathic doctors work along-side medical oncologists and things like melatonin and Vitamin C are given as standard therapies to patients undergoing chemotherapy or radiation. Of course there are specific interactions that must be avoided and a Naturopathic Doctor who is skilled in integrative cancer treatments will be able to guide you to develop a safe and effective plan. You must have professional guidance when developing a treatment plan in the complicated clinical context of cancer.

One of the most common natural therapies given to patients undergoing chemotherapy is melatonin. I have heard on numerous occasions from patients who were warned from the cancer agency pharmacist that melatonin is contraindicated during chemotherapy and radiation because it is an antioxidant. What I find so bizarre about this statement is that virtually all of the available scientific literature literally says the opposite and strongly supports the use of melatonin with chemotherapy and radiation. The position of scaring patients about melatonin is not grounded in scientific evidence, they take this position because from a legal perspective it is easier to say avoid any and all antioxidants.

What does the research say about melatonin used in combination with chemotherapy? Several randomized double blind trials have tested patients with lung cancer who were treated with chemotherapy alone or chemotherapy in combination with melatonin. The melatonin group not only lived longer they also had significantly better quality of life when compared to the group not given melatonin^15,16,17. Melatonin has been consistently shown to enhance the effects of chemotherapy while reducing side effects^18,19,20,25. It is however important to point out that not all cancers are the same and melatonin is not indicated for all cancers. In fact, it is contraindicated with many blood cancers such as leukemia.

What does the scientific literature actually say about combining melatonin with radiation therapy? Patients who concurrently take melatonin during radiation therapy for glioblastoma live significantly longer than those who just received radiation therapy²¹. Melatonin helps to protect damage to the immune system during radiation^22,23,24. Although melatonin is a well documented antioxidant, there are numerous studies which demonstrate that melatonin actually makes cancer cells more sensitive to the effects of radiation^26,27.

When used appropriately certain antioxidants such as melatonin can reduce side effects from conventional cancer therapies without interfering with their effectiveness. Healthy cells need antioxidants too and when you consume natural sources of antioxidants the net effect is that it protects healthy cells much more than cancer cells. Ultimately this makes the drugs work just as well and the healthy cells are less damaged from the drug. When you consume a diet rich in antioxidants, the antioxidant capacity of your blood increases dramatically and the research clearly demonstrates that this is a good thing during chemotherapy and radiation.

Lets take a moment to look at the data about melatonin and its activity as an antioxidant. After consuming 80mg of melatonin the serum levels peak at approximately 100,000 pg/mL before rapidly dropping by the end of the day². The standard dose of melatonin given during chemotherapy or radiation is 20mg. Based on this number it is fair to assume that the amount of melatonin in the blood would be approximately 25,000 pg/mL. At first glance this seems like a shockingly high number. It is well documented that when patients eat a diet high in antioxidant rich foods, that the antioxidant capacity of their blood increases and some of this is due to the melatonin in the food³. In one well controlled study after consuming approximately 1L of orange juice the participants had serum melatonin levels rise from 40 to 150 pg/mL¹. This is still 150 times less than values that would be expected after consuming 20mg of melatonin.

The data must be taken into the proper context. True antioxidant capacity in the blood is never determined by one single molecule. It is the entire antioxidant network that gives the blood the capacity to neutralize free radicals. There is a potent synergy between hundreds of different antioxidants which counteracts oxidative damage in a balanced way. Each molecule on its own is only one small piece of the complicated antioxidant network. The mechanism by which melatonin neutralizes free radicals is very different from that of Vitamin C and Vitamin E⁵. Melatonin is often described in the literature as a terminal antioxidant which distinguishes itself from so called opportunistic antioxidants. The bottom line is that the addition of a single antioxidant does not necessarily impact the entire antioxidant capacity of the blood in a linear fashion.

This next section is a bit heavy in math but I feel that it is important to break down these details. Melatonin is approximately 2.04 times more potent of an antioxidant than a molecule called Trolox. This molecule Trolox is often used as a standard to measure the antioxidant capacity in the blood. Blueberries, which are best known for their antioxidant capacity have an ORAC value of 6552. This means that 100g of blueberries will have the same antioxidant capacity as 6552 micromoles of Trolox. Based on this information it is easy to calculate that 15.26mg of blueberries is the equivalent antioxidant capacity of 1 micromol of Trolox. If you convert these values to make it relevant to melatonin, each mg of melatonin is equivalent to 31.13g of blueberries. The standard dose of 20mg of melatonin during chemotherapy is the equivalent of a patient eating 622.71g of blueberries. In other words, if you eat a little over 1 pound of blueberries this should have the equivalent antioxidant effect as 20mg of melatonin.

There is no evidence to suggest that antioxidants from natural sources are dangerous during chemotherapy or radiation. In fact, virtually all of the literature clearly states that it is beneficial to get antioxidants from natural sources. By consuming antioxidant rich foods, patients have fewer side effects during conventional cancer treatments. Many studies have also clearly demonstrated that these foods do not interfere with the effectiveness of these therapies^{6,7,8,9,10,11}. The debate is around synthetic supplementation with high doses of antioxidants during chemotherapy and radiation. Natural sources are well established as beneficial in these cases, as they protect healthy cells without interfering with the effects of conventional therapies⁹.

Blueberries are a great source of nutrients and they provide a balanced antioxidant support that is synergistic with chemotherapy and radiation. What is particularly interesting is that wild blueberries are much more effective at neutralizing free radicals than cultivated blueberries. Depending on which measurements you use, in some cases the wild blueberries have almost double the antioxidant capacity. So make sure you eat your blueberries and give your cells the nutrients they need!

Dr. Adam McLeod is a Naturopathic Doctor (ND), BSc. (Hon) Molecular biology, Motivational Speaker and International Best Selling Author. He currently practices at his clinic in Vancouver, British Columbia where he focuses on integrative cancer care. https://www.yaletownnaturopathic.com

References:

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