Antioxidants may Prevent "Chemo-Brain"

A new animal study shows that antioxidant therapy may protect against memory and attention problems commonly seen in cancer patients who are undergoing chemotherapy.

When cancer treatment interferes with thinking, it is sometimes called "chemo-brain" or "chemo-fog." Chemo-brain is estimated to affect about 20-30 percent of chemotherapy patients, but its cause remains unknown. The condition is generally mild and symptoms gradually improve over time after chemotherapy is completed. 

Researchers from West Virginia University School of Medicine tested whether injections with the antioxidant N-acetyl cysteine (NAC) could prevent chemo-related memory changes in rats.

One group of rats received two common cancer drugs, doxorubicin (Adriamycin®) and cyclophosphamide (Cytoxan®), four times weekly. Compared to the control animals, the rats that received chemotherapy had lower memory scores, indicating chemo-brain.

However, chemo-brain was prevented when rats received NAC injections three times weekly during chemotherapy.

Although these results, published in the journal Metabolic Brain Disease, are promising, additional research in humans is needed before recommendations can be made in humans. In the meantime, cancer patients should not take antioxidant supplements unless under the supervision of their healthcare providers. There has been concern that antioxidants may theoretically interfere with the effectiveness of chemotherapy in humans, but study results are inconclusive.

In a related review article, researchers have found that antioxidant supplementation during chemotherapy may reduce toxicities, thereby reducing side effects. While most studies showed that antioxidants had positive effects on toxicity, statistical power and poor study quality were concerns with some studies.

Comments

[david c.]

This study seems to show yet another benefit of these wonderful antioxidants. Antioxidants are also thought to actually prevent cancer by neutralizing free radicals as the natural byproduct of normal cell processes. Free radicals are molecules with incomplete electron shells that make them more chemically reactive than those with complete electron shells. Exposure to various environmental factors, including tobacco smoke and radiation, can also lead to free radical formation.

In humans, the most common form of free radicals is oxygen. When an oxygen molecule (O2) becomes electrically charged or "radicalized," it tries to steal electrons from other molecules, causing damage to the DNA and other molecules. Over time, such damage may become irreversible and lead to diseases, including cancer. Antioxidants are often described as "mopping up" free radicals; meaning they neutralize the electrical charge and prevent the free radical from taking electrons from other molecules.

[Yvonne]

N-acetyl-cysteine is commonly used to detoxify acetaminophen (Tylenol) overdoses. When a patient takes more than four grams of acetaminophen per day, liver damage begins to occur. The production of NAPQI, the chemical that causes the liver damage, occurs through a metabolic pathway in which only two percent of the acetaminophen is metabolized. After NAPQI is formed, glutathione normally binds to NAPQI to form a non-toxic metabolite, to be excreted via urination. However, when a patient takes more than four grams per day, the body runs out of glutathione to detoxify the NAPQI, leading to a build up of the toxin, thus leading to “Tylenol toxicity." N-acetyl-cysteine has sulfahydryl groups that act to detoxify NAPQI in place of glutathione.

[Hank]

I am concerned with the theoretic interference of the chemo by the antioxidants in humans. Cancer can be very difficult to treat and having to increase the dose to offset a reduced effect could cause increase adverse effects. The chemo that the rats received in the study can cause particularly serious side effects. Doxorubicin in particular has a limited lifetime dose, so interfering with that could be problematic in treatment.

[LK]

It sounds like this condition can be debilitating to some patients, so it's nice to know there are active studies going on to try and stop it. Here is a little background on chemo-brain. Chemo-brain or chemo-fog refers to cognitive changes during and after cancer diagnosis and treatment. There may or may not be a relationship to chemotherapy. It can affect one in the following ways: word finding, memory, multitasking, learning and processing speed. The chemo-fog can last for years, even after ceasing treatment. Does anyone know someone who has experienced this? Oddly enough, I had not heard of the term until this article.

[liz]

N-acetyl cysteine functions as a detoxifier and antioxidant. It is used as liver protectant, as well as to break-up pulmonary and bronchial mucous. It is recommended to be taken with Vitamin C to help keep the glutathione that is produced from the cysteine in its reduced form so that it can continue to act as an antioxidant. There has been evidence that NAC has the ability to modulate a variety of DNA damage and cancer related end-points.

Although “Chemo-Brain” is generally mild and symptoms gradually improves over time, for some, the cognitive problem is long-term. I think the current findings warrant for further research in humans.

[dave]

I’m glad that this article cautions against the potential harm of antioxidant compounds. While we tend to view them as universally beneficial, these are, in fact, biologically active compounds (which is why we take them!), and there are a lot of factors that may influence the effect they have on health status and disease outcomes. For example, the point in time at which antioxidants are introduced may influence the type of effect they have. While an antioxidant may have a beneficial effect at one point in time, there is some evidence that it may have harmful effects at another point in time. It’s definitely advisable to avoid taking anything except under medical supervision.

[charlotte]

It's good to know that there is a natural option to treating this frustrating problem, but I feel that the concern of antioxidants theoretically interfering with chemotherapy will prevent this from becoming a mainstream treatment. Chemotherapy is not 100 percent effective as it is, and the possibility of decreasing chemo’s effectiveness would really deter patients and their families from wanting to use such products. I’ve seen “chemo brain” on a few occasions, and it can impair your cognitive function even after chemotherapy, sometimes for years. Perhaps using antioxidants on the days the patient is not receiving chemo would not affect the effectiveness of the chemotherapy?

[Sheri]

It is scary to think that chemo-brain, or cognitive effects from chemotherapy, can be felt even after the chemotherapy is over. I had never heard of this condition before. According to the Mayo Clinic, some of the aspects affected by chemo-brain is memory, learning new things and processing speeds. Hopefully, antioxidant N-acetyl cysteine (NAC) can provide some sort of relief from these symptoms with more research.

[Tom M]

Dave, I think you bring up a great point about the potential harm that these antioxidants could cause. Although I think it’s great that research is being done to understand how antioxidant N-acetyl cysteine (NAC) could prevent the effects of chemotherapy on memory, antioxidants can act in other ways, and more research definitely has to be done in order to better understand how they are working in the body in this situation.

[Darcy]

Yvonne, I didn't know that antioxidant N-acetyl cysteine (NAC) could be used as a detoxifying agent. Does anyone know if it is used for anything else other than acetaminophen overdoses? And how is it generally administered?

[Kristy]

Within the 33 studies on concurrent use of specific antioxidants, there was no mention of the diets of these patients. Many foods are antioxidant-rich, and it is possible that in those nine studies where no difference was noted that some patients studies may have consumed antioxidant-rich foods in their diets. It would be interesting to see the post-treatment impact of antioxidants on “chemo-brain” as well.

[SUMA]

In some patients, chemotherapy has been associated with cognitive problems — problems with thinking, learning and memory. Cognitive deficits may include forgetfulness or difficulty concentrating. Problems with memory and concentration can be very frustrating for patients undergoing chemotherapy.

The American Cancer Society published an article in 2004 stating how in the past, doctors assumed chemo-brain was a byproduct of other chemotherapy side effects like anemia, fatigue or depression. Treating these conditions often resolved the problem. The challenge was, and is, helping those patients whose symptoms are not caused by one of these factors. The results of this study are promising and warrant further research to determine the role antioxidants can play in helping patients deal with chemo-brain. Other factors to consider are that antioxidants are found in leafy vegetables, fruits, wine and chocolate. Antioxidants can also be found in certain vitamins and minerals such as vitamins A, C and E; zinc and selenium.

Antioxidants can minimize free radical damage. A diet containing a balance of the various forms of antioxidants will maintain overall good health, and could even impact serious diseases. The American Cancer Society encourages people to eat five servings of fruits and vegetables per day and emphasizes the benefits of getting antioxidants through foods rather than supplements. The key "is to eat a variety of fruits, vegetables, and nuts to ensure that we are taking advantage of all the health benefits that antioxidants can provide."

I do agree with the authors that “cancer patients should not take antioxidant supplements unless under the supervision of their healthcare providers, as there has been concern that antioxidants may theoretically interfere with the effectiveness of chemotherapy in humans”.

[Tamara .S]

This study indicates that a diet rich in antioxidants in general has neuroprotective effects and might contribute to the lower incidence of neuro-degenerative diseases

[charlene]

Darcy, N-acetyl cysteine is used to treat other causes of liver failure besides from acetaminophen overdose. It's also a chelating agent for heavy-metal toxicity from heavy metals such as lead, mercury and arsenic. It may reduce the risk of developing colon cancer and also helps break up mucoproteins in lung mucus. It's thought to increase absorption of glutathione, which helps transport nutrients to several types of immune cells. Because of this, N-acetyl cysteine is also being investigated as a cure for AIDS.

[tom]

The Mayo Clinic also says that chemo-brain may not actually be a direct result of chemotherapy, but it may also be related to stress and fluctuating hormone levels. While the rats used in the study did have cognitive impairment, this may not be the exact same symptom being described by human cancer patients. It's good that this article stresses the possible dangers of taking antioxidant supplements as a cancer patient until further research is conclusive.

[Sarah]

It seems like the best way to get the antioxidants you need is through the fruits and vegetables you eat and not resorting to antioxidant supplements. It might pose a risk for cancer patients, but should others be taking antioxidant supplements? I am always weary of putting something into my body if I don’t really need it.

[Becca]

Even though antioxidants are generally looked at as great for us because of their ability to fight free radicals, I wouldn’t feel comfortable with the mixed study results in cancer patients until further studies prove it is safe.

[Hosh]

N-acetyl-cysteine can also be used to prevent acute kidney failure in patients receiving non-ionic contrast media. Non-ionic contrast media is used to help radiologist easily view parts of the body during MRI and CT scans. This happens to be an unlabeled use for the drug, so maybe some others exist as well. Does anyone know if there are any other antioxidants that may have similar actions?

[lauren e.]

In an article that was published in the April 29, 2007 issue of The New York Times, it states that chemo-brain is a very real phenomenon that can affect one’s quality of life, years after cancer treatment. Some examples of “mental fog” by breast cancer survivors: one woman had to ask her husband which toothbrush was hers, another women found five unopened gallons of milk in her fridge and had no recollection of buying the first four. At a family dinner, another woman filled her water glasses with turkey gravy. The article also says that some oncologists are offering acupuncture and stimulants usually used for attention deficit disorder to combat chemo-brain. Many of these patients improve after initial treatment; only about 15 percent still have effects years later.

[karen]

Since people have basically covered everything that needs to be said about antioxidants, I figure I’d give a little background on doxorubicin (the chemo drug given to the rats) so that we can perhaps speculate why chemo-brain occurs in the first place.

Doxorubicin’s trade name is Adriamycin®. It is an anthracycline antibiotic that intercalates DNA. It is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft-tissue sarcomas. The drug is administered intravenously.

The exact mechanism of action of doxorubicin is complex and still somewhat unclear, though it is thought to interact with DNA by intercalation. Doxorubicin is known to interact with DNA by intercalation and inhibition of macromolecular biosynthesis. This inhibits the progression of the enzyme topoisomerase II, which unwinds DNA for transcription. Doxorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication.

[Bill]

As Charlene stated, NAC is also used as a mucolytic. One of the uses of this mucolytic is for the pulmonary manifestations of cystic fibrosis. Cystic fibrosis is characterized by a defect in the CFTR gene which creates a protein that regulates chloride ion transport through the cells' interior and exterior fluids. When a defect in this gene leads to defective CFTR protein, chloride accumulates either inside or outside of the cell, depending on the cell type (skin, lung, digestive tract, etc.), leading to ion imbalances. In the pulmonary system, this imbalance leads to thickening of the mucus in the respiratory tract, allowing bacteria to grow within, hence the need for a mucolytic such as NAC.

[Anna H.]

It's interesting, but very controversial in nature. I hope further studies can help solve the contradictory information presented in the article about antioxidants and how their free radicals scavengers may help relieve toxicity and side effects caused by chemotherapy.

[Anna H.]

If the study of antioxidants confirmed, I think it will be a positive move for treatment - at least for the short-term treatment of memory loss. As long as it does not prolong the painful (emotionally, physically or mentally) process of chemo, then I do believe it is worth it. The plus side of this treatment is the reduction of side effects during chemotherapy. Cancer patients go through enough painful events and even reducing the slightest of pain is considered positive.

[Rollie]

Chemo-brain can be a debilitating side effect from chemotherapy. I am glad that there may be a treatment for it. Hopefully, more studies will confirm the use of antioxidants in this state. If antioxidants reduce the toxicity of the chemotherapy drugs, I wonder if the chemo drugs would be as effective? Part of why they work on cancer cells is because they do have some toxicity.

The second trial was a review of antioxidant supplementation in cancer; however, only two of the 33 trials used N-acetyl cysteine (NAC). The most common antioxidants in the trials were glutathione and melatonin.

[CC]

In reference to Lauren's comment, I've heard of acupuncture having great results, but to resolve chemo-brain after one treatment? That is amazing! Chemo-brain is a major quality-of-life issue associated with chemotherapy. Chemo-brain is such a serious side effect that it can actually influence treatment decisions, resulting in patients rejecting or switching to different regimens that may not be as effective for their particular cancer. More research needs to be done to help find treatments or methods to help prevent or lessen chemo-brain.