Do Supplements Interfere With Chemotherapy?

Should You Avoid Supplement Use During Chemotherapy?

cancerSince much of my research career was devoted to cancer research, specifically developing new chemotherapeutic drugs for treating cancer, many of you have asked me the question: “Do food supplements interfere with chemotherapy?”

My answer has always been that it is theoretically possible, but that we don’t really know the answer because the necessary studies have not been done.

However, I do know that most cancer drugs are retained in the body for a short period of time. So, my pragmatic advice has always been to avoid supplementation for a day or two before to a day or two after each round of chemotherapy. That is a strategy designed to minimize the possibility that supplementation would interfere with chemotherapy and maximize the possibility that supplementation might aid in recovery between rounds of chemotherapy.

That is why I was interested when I saw the recent headlines claiming certain supplements may interfere with chemotherapy for breast cancer. I wanted to find out if someone had finally done a definitive study on the effect of supplementation on chemotherapy.

So, I have reviewed the study (CB Ambrosone et al, Journal of Clinical Oncology, 38, 804-815, 2020) behind the headlines and will share what I discovered.

How Was The Study Done?

Clinical StudyThis study was an offshoot of a much larger Phase III clinical trial designed to determine the best schedule for administering three drugs (doxorubicin, cyclophosphamide, and paclitaxel) to patients with high-risk early-stage breast cancer.

The 1,134 patients enrolled in this study were given questionnaires on their use of supplements when they registered for the study to determine supplement use prior to the study. They were also given questionnaires when they completed chemotherapy to determine supplement use during chemotherapy.

The questionnaires documented use of:

  • Multivitamins
  • The antioxidants vitamin C, vitamin A, vitamin E, carotenoids, and coenzyme Q10.
  • Vitamin D.
  • The B vitamins vitamin B6, vitamin B12, and folic acid.
  • The minerals iron and calcium.
  • Omega-3 fatty acids.
  • Glucosamine, melatonin, and acidophilus.

Recurrence of the breast cancer and death from breast cancer were measured 6 months after chemotherapy ended.

Do Supplements Interfere With Chemotherapy?

Questioning WomanThe study reported:

  • The number of patients using individual antioxidant supplements was too low to determine whether individual antioxidants had any effect on treatment outcomes.
  • When the patients using any antioxidant supplement were pooled into a single group, there was a nonsignificant association between antioxidant supplement use during chemotherapy and an increased risk of breast cancer recurrence and death from breast cancer.
  • Iron use during chemotherapy was significant associated with an increased risk of breast cancer recurrence.
  • Vitamin B12 use during chemotherapy was significantly associated with increased risk of breast cancer recurrence and death from breast cancer.
  • Multivitamin use was not associated with either recurrence or death from breast cancer.
  • The number of patients using the other supplements was too low to determine whether those supplements had any effect on treatment outcomes.

The authors concluded: “Associations between survival outcomes and use of antioxidant and other dietary supplements are consistent with recommendations for caution among patients when considering the use of supplements, other than a multivitamin, during chemotherapy.”

This is the conclusion that generated the headlines you may have seen.

However, in their discussion the authors conceded that a previous review concluded that, “…insufficient evidence existed with regard to the safety of dietary supplements [during chemotherapy] to make recommendations, and that still may be the case.”

I will discuss the reasons for their disclaimer below. However, I will point out that disclaimers like this never seem to make it into the headlines you read.

What Are The Strengths And Weaknesses Of This Study?

strengths and weaknessesThe only strength of this study is that it was performed in the context of an ongoing clinical trial, with surveys conducted before chemotherapy and during chemotherapy to assess supplement use.

However, the study had multiple weaknesses that limit the ability to draw any firm conclusions from the study.

#1: The number of people using supplements in this study was very small. For example:

  • Only 200 people took any antioxidants during chemotherapy.
  • Only 137 people took a vitamin B12 supplement during chemotherapy.
  • Only 109 people took an iron supplement during chemotherapy.

To put this into perspective, if a drug company were submitting a new drug for approval to the FDA, they would be required to submit data from ~50-100-fold more cancer patients to prove that the drug was effective.

With this small number of supplement users, even “statistically significant” observations are questionable.

In contrast, the number of people taking a multivitamin during chemotherapy was 497. Thus, those data were a little stronger than the data for individual supplements.

#2: They did not ask why people were taking supplements. It turns out that the patients who used supplements were older and sicker. They were more likely to be overweight and to have type 2 diabetes.

These are patients who are also more likely to have poor outcomes from chemotherapy. The authors tried to correct for that, but it is virtually impossible to make these corrections when the number of patients taking supplements is so low.

#3: They did not ask about the dose of supplements people were taking.

  • Multivitamins typically contain RDA levels of antioxidants and vitamin B12, so it would be safe to assume that RDA levels of antioxidants and vitamin B12 are safe during chemotherapy.
  • Approximately 50% of the women in the study were premenopausal, so it is likely that they were taking a multivitamin with iron. That suggests that RDA levels of iron are safe during chemotherapy for premenopausal women.

In short, the association between supplement use and poorer outcomes from chemotherapy is tenuous. If there is any association, it is likely with high dose individual supplements rather the lower levels of the same nutrients found in a multivitamin.

Is An Effect Of Supplement Use On Chemotherapy Plausible?

As a biochemist, the next question I ask is whether there is a plausible mechanism for an effect of any of these Look forsupplements on chemotherapy outcomes.

  • For two of the drugs in the regimen (paclitaxel and cyclophosphamide), free radical formation may contribute to their effectiveness, but it is not their main mechanism of action. Thus, it is plausible that high dose antioxidant supplements could make these drugs less effective, but the effect should be relatively small.
  • Tumors require high amounts of iron for proliferation, so it is plausible that excess iron could make tumors more resistant to chemotherapy. However, for premenopausal women, multivitamins with iron did not interfere with the drugs used in this study. Thus, it appears likely that RDA levels of iron, where appropriate, do not interfere with chemotherapy.
  • The authors said that the reason for the observed effects of vitamin B12 on chemotherapy in their study “remains to be understood”. However, the answer might be found in the dosage of vitamin B12. A previous study reported that doses of vitamin B12 that were greater than 20 times the RDA increased the risk of lung cancer.

If people in this study were taking doses of vitamin B12 in excess of 20 times the RDA, it would provide a plausible explanation for B12 interfering with chemotherapy. If not, there is no known explanation. In any case, I do not recommend taking such high doses of any supplement.

Should You Avoid Supplement Use During Chemotherapy?

AvoidNow, let’s get back to the original question: “Should you avoid supplement use during chemotherapy?” If you read the headlines saying, “Supplement Use During Chemotherapy May Be Risky”, you might think that the answer is an unqualified yes. That is also what your doctor is likely to think.

However, when you analyze the study behind the headlines you realize that the evidence supporting the headlines is very weak.

So, that puts us back to where we were before the study was published. Simply put:

  • It is theoretically possible that supplements interfere with chemotherapy, but we don’t know for sure.
  • A pragmatic approach is to avoid supplementation for a day or two before to a day or two after each round of chemotherapy. This is a strategy designed to minimize the possibility that supplementation would interfere with chemotherapy and maximize the possibility that supplementation might aid in recovery between rounds of chemotherapy.

Note: This is generic advice. I am not a medical doctor, so it would be unethical for me to provide individualized advice on how to minimize interactions between supplements and chemotherapy. What I recommend is that you ask your doctor whether my generic recommendations make sense for your cancer and your drug regimen.

If this study advanced our knowledge at all, it would be that:

  • The supplements most likely to interfere with chemotherapy appear to be high dose antioxidants, vitamin B12, and iron supplements.
  • Multivitamins, even multivitamins with iron when appropriate, are unlikely to interfere with chemotherapy.

The Bottom Line 

Recent headlines have warned, “Supplement Use During Chemotherapy May Be Risky”. Is that true?

However, when you analyze the study behind the headlines you realize that the evidence supporting the headlines is very weak.

So, that puts us back to where we were before the study was published. Simply put:

  • It is theoretically possible that supplements interfere with chemotherapy, but we don’t know for sure.
  • A pragmatic approach is to avoid supplementation for a day or two before to a day or two after each round of chemotherapy. This is a strategy designed to minimize the possibility that supplementation would interfere with chemotherapy and maximize the possibility that supplementation might aid in recovery between rounds of chemotherapy.

Note: This is generic advice. I am not a medical doctor, so it would be unethical for me to provide individualized advice on how to minimize interactions between supplements and the chemotherapy drugs you are on. What I recommend is that you ask your doctor whether my generic recommendations make sense for your cancer and your drug regimen.

If this study advanced our knowledge at all, it would be that:

  • The supplements most likely to interfere with chemotherapy appear to be high dose antioxidants, vitamin B12, and iron supplements.
  • Multivitamins, even multivitamins with iron when appropriate, are unlikely to interfere with chemotherapy.

For more details read the article above.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

 

Does Fiber Reduce Breast Cancer Risk?

Start Young And Finish Strong

Vegan FoodsThe idea that dietary fiber reduces the risk of breast cancer has been around for a long time. But it is controversial. It has been difficult to prove.

Part of the difficulty arises from what scientists call confounding variables. What do I mean by confounding variables? Let me explain.

A high fiber diet is usually a primarily plant-based diet. Plant foods contain much more than just fiber. They are full of antioxidants and phytonutrients. A primarily plant-based diet is, by definition, low in refined grains. It is usually low in sugar and saturated fat as well.

People who eat primarily plant-based diets are often health conscious. They tend to exercise more, weigh less, and smoke less than the general public.

Each of these things are confounding variables. They could reduce the risk of breast cancer on their own. That confounds (makes it more difficult to interpret) the data. Was the reduction in breast cancer risk due to the high fiber diet or to these factors that go along with a high fiber diet?

It is possible to correct for these confounding variables statistically, but that requires a very large study (a large population group) for the correction to be accurate. Large studies are expensive. Thus, you tend to end up with lots of small studies. And once they have been corrected for confounding variables, small studies give conflicting results. Some show a benefit of fiber. Some do not.

That is why this study (MS Farvid et al, Cancer, DOI: 10.1002/cncr.32816) is important. It is a meta-analysis of 20 clinical studies with almost 2 million women.

How Was The Study Done?

Clinical StudyThe meta-analysis combined data from 20 clinical studies with 1,994,910 women. Fiber intake was calculated from a food frequency questionnaire administered at the beginning of the study for all except one study that used 24-hour dietary records administered at the beginning of the study.

  • Study duration ranged from 2 to 20 years. Nine of the studies (1.37 million women) lasted for 10 years or more.
  • Four studies reported results for premenopausal breast cancer, fifteen studies reported results for postmenopausal breast cancer, and one study reported results for both.

Does Fiber Reduce Breast Cancer Risk?

breast cancerAfter correcting for confounding variables, the results of the study were as follows:

  • When comparing the highest intake with the lowest intake, total fiber consumption was associated with an 8% lower risk of breast cancer.
  • The effect was stronger for premenopausal breast cancer (18%) than for postmenopausal breast cancer (9%).
  • The effect was greater with soluble fiber (10% decreased risk) than for insoluble fiber (7% decreased risk).
    • Note: All plant foods contain a mixture of soluble fiber and insoluble fiber. However, the common foods richest in soluble fiber are fruits, oatmeal, nuts, beans, peas, and lentils.

The authors concluded, “A random-effects meta-analysis of prospective observational studies demonstrated that high total fiber consumption was associated with a reduced risk of breast cancer. This finding was consistent for soluble fiber as well as for women with premenopausal and postmenopausal cancer.”

Start Young And Finish Strong

Mother & Daughter Eating ApplesAn 8% risk reduction doesn’t seem like very much, but the 18% risk reduction in premenopausal breast cancer caught my eye. With a little digging I found a study (MS Farvid et al, Pediatrics 137, March 2016: e20151226) that focused on the effect of fiber intake in young women on their subsequent risk developing both premenopausal and postmenopausal breast cancer. This was, in fact, one of the studies included in the meta-analysis I described above.

This study followed 90,534 women (mean age 36 years) for 20 years. The women competed a food frequency questionnaire at enrollment and every four years thereafter. They also completed a questionnaire about their diet during their teenage years.

When comparing the highest versus the lowest fiber intake:

  • High fiber intake reduced total breast cancer risk by 19%.
    • Postmenopausal breast cancer risk was reduced by 13%.
    • Premenopausal breast cancer risk was reduced by 23%.

Interestingly, only 34% of women who consumed high fiber diets during their teenage years continued to consume high fiber diets as young adults. However, high fiber diets in the teenage years were important. When they looked at teenage diets:

  • High fiber intake reduced total breast cancer risk by 16%.
    • Postmenopausal breast cancer risk was reduced by 15%.
    • Premenopausal breast cancer risk was reduced by 25%.

Other important observations from this study were:

  • There was a 13% decrease in breast cancer risk for every 10 gram increase in fiber intake.
    • 10 grams of fiber is equivalent to one apple plus two slices of 100% whole wheat toast or half a cup of cooked kidney beans plus half a cup of cooked cauliflower or squash.
  • Both soluble fiber (14% decreased risk) and insoluble fiber (20% decreased risk) were effective.
    • In terms of foods, the most significant effects were seen with fruits and vegetables.

The authors concluded, “Our findings support the hypothesis that higher fiber intakes reduce breast cancer risk and suggest that intake during adolescence and early adulthood may be particularly important.”

What Does This Mean For You?

Questioning WomanAs I said before, an 8% decrease in breast cancer risk may not sound like much. You might be tempted to say, “Why bother? Why should I give up my favorite processed and convenience foods and switch to a more whole food, plant-based diet?”

Here are some thoughts to consider:

1) As I mentioned above, there are side benefits to a plant-based diet.

    • Plant based diets have a lower caloric density, so you are less likely to be overweight.
    • Your intake of antioxidants and phytonutrients is increased.
    • Plant foods feed beneficial gut bacteria.
    • Your diet is likely to be lower in sugar, highly processed foods, and saturated fat.

All these factors decrease your risk of developing breast cancer, but they were statistically factored out in calculating the 8% reduction in risk. In other words, the 8% reduction in risk was based on fiber intake only. When you consider all the beneficial effects that accompany a high fiber diet, your actual reduction in risk is likely to be substantially more than 8%.

2) When you consume a high fiber diet, your risk of developing premenopausal breast cancer is decreased by 18%. That is twice the risk reduction seen for postmenopausal breast cancer. This is consistent with several other studies showing the premenopausal breast cancer is more influenced by diet than postmenopausal breast cancer. There are a couple of likely explanations for this.

    • By the time they reach menopause women are more likely to be overweight and some of those fat calls accumulate in breast tissue. Those fat cells continue to produce estrogen after menopause. Even worse, that estrogen is produced right next to the breast cells, where it can do the maximum damage.
    • Mutations accumulate in breast tissue as we age, and some of those mutations increase the risk of breast cancer.

3) When you start consuming a healthy, high fiber diet early in life your risk reduction is much greater (a 13-15% decreased risk of developing postmenopausal breast cancer and a 23-25% decreased risk of developing premenopausal breast cancer). Now, we are talking about numbers that should get your attention!

Plus, these numbers are based on fiber intake only. Once again, when you consider all the other benefits of a high fiber diet, your real risk reduction is likely to be much greater.

In closing I should mention that none of the studies were done with fiber supplements. A fiber supplement may help you be more regular, but there is no evidence that a fiber supplement will reduce your risk of breast cancer.

The Bottom Line

Two recent studies have looked at the effect of fiber intake on the risk of developing breast cancer.

The first study showed that:

  • High fiber diets decreased the overall risk of breast cancer by 8% and the risk of premenopausal breast cancer by 18%.
  • As I describe in the article above, these reductions in risk were based on fiber intake only. If you consider all the side benefits of a high fiber diet, the actual risk reduction is likely to be much greater.

The second study looked at fiber intake during adolescence and early adulthood. It found that when high fiber diets were started early in life:

  • High fiber diets decreased the overall risk of breast cancer by 13-15% and the risk of premenopausal breast cancer by 23-25%.
  • Once again, if you consider all the side benefits of a high fiber diet, the actual risk reduction is likely to be much greater.

The authors of both studies concluded that high fiber diets reduce the risk of developing breast cancer. The risk reduction is greater for premenopausal breast cancer than for postmenopausal breast cancer. Finally, the risk reduction is greatest when high fiber diets are started early in life.

For more details read the article above.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

Diet And Cancer Risk

What Can You Do To Reduce Your Risk Of Cancer?

Magic WandIt seems like everyone has a magic pill, essential oil, food, or diet that prevents cancer. It doesn’t take a genius to figure out that all the claims can’t be true. No wonder you are confused. You want to know:

  • Which of these claims are true?
  • What can you do to reduce your risk of cancer?

These aren’t trivial questions.

  • Cancer is the second leading cause of death in this country, and some experts predict it will surpass heart disease as the leading cause of death in the near future.
  • While cancer treatments have become much more effective in the past few decades, these treatment successes are often associated with severe side-effects, enormous expense, or both.

That is why I was intrigued by a recent study (FF Zhang et al, JNCI Cancer Spectrum (2019) 3(2): pkz034) on diet and cancer that came from the prestigious Friedman School of Nutrition and Public Policy at Tufts University. This study asked two important questions:

  • How many newly diagnosed cancer cases could have been prevented by changes in the American diet? This is something the authors referred to as the “preventable cancer burden associated with poor diet”.
  • Which foods increased or decreased the risk of cancer? This, of course, is the most useful information for you and me.

Diet And Cancer Risk

Diet And CancerThis study estimated that 80,110 new cancer cases among US adults 20 and older could be primarily attributed to poor diet. While poor diet contributes to many more cancers, the authors of this study felt 80,110 represented the number of cancer cases that were clearly preventable by some simple dietary changes.

While all cancers were affected by diet to some degree, the cancers most affected by poor diet were:

  • Colon cancer (65% of cases)
  • Mouth and throat cancer (18% of cases)
  • Endometrial cancer (4.0% of cases)
  • Breast cancer (3.8% of cases)

When the diet was broken down into individual food groups:

  • Low intake of whole grains was associated with the largest number of preventable cancer cases (35% of cases). This was followed by.
  • Low intake of dairy foods (22% of cases).
  • High intake of processed meats (18% of cases).
  • Low intake of vegetables (16% of cases).
  • Low intake of fruits (10% of cases).
  • High intake of red meat (7.1% of cases).
  • High intake of sugar sweetened beverages (4.0% of cases).

Of the diet-associated cancer cases, the scientists who lead the study estimated that 84% of them represented a direct effect of diet on cancer risk. The dietary factors most likely to directly increase the risk of cancer were:

  • Low intake of whole grains.
  • Low intake of dairy foods.
  • High intake of processed meats.

The scientists estimated that 16% of diet-associated cancer cases were “mediated by obesity”. In layman’s terms, this means that diet increased the risk of obesity and obesity increased the risk of cancer. The dietary factors most likely to increase the risk of obesity-mediated cancers were:

  • High intake of sugar sweetened beverages.
  • Low intake of fruits.

The authors concluded: “More than 80,000 new cancer cases [per year] are estimated to be associated with suboptimal diet among US adults…Our findings underscore the need for reducing cancer burden in the United States by improving the intake of key food groups and nutrients of Americans.”

What Does This Mean For You?

Questioning ManThese findings aren’t novel. Many previous studies have come to the same conclusions. However, many people find these recommendations to be confusing. Should they increase their intake of certain foods? Should they follow some sort of magic diet?

Perhaps we need to get away from the magic food concept. We need to understand that every time we increase one food in our diet, we exclude other foods. We need to step back and look at the overall diet.

Let me break down the recommendations from this study into three categories: foods we should eliminate from our diet, foods we should include in our diet, and foods we should balance in our diet.

Foods we should eliminate from our diet:

  • Sugar Sweetened Beverages. They provide no nutritional benefit, and the sugar in most beverages rushes into our bloodstream and overwhelms our body’s ability to utilize it in a healthy way. This leads to obesity, diabetes, and a host of other health issues.
    • Public enemy number one is sodas. However, this category also includes fruit juices, sweetened teas and energy drinks, and sugary processed foods.
    • This category also includes diet sodas. For reasons we don’t completely understand, diet sodas appear to be just as likely to lead to obesity, diabetes, and heart disease as sugar sweetened sodas. I have discussed the proposed explanations of this phenomenon in a recent issue of “Health Tips From the Professor”.
    • Sugar, however, is not the enemy. Sugar found naturally in fruits and other whole foods enters the bloodstream slowly and is metabolized in healthy ways by the body. I have discussed this in another issue  of “Health Tips From the Professor”. This is what I mean by restoring balance in our diet. Decreasing the sugar intake from sugar sweetened beverages and increasing sugar intake from fruits is associated with a decreased risk of obesity and obesity-related cancers.
  • Processed Meats. The evidence is overwhelming at this point that processed meats directly increase the risk of cancer.
    • If you have trouble completely eliminating processed meats from your diet, my advice is to minimize them and consume them only in the context of an overall healthy diet. Personally, I still consume bacon occasionally as flavoring for a healthy green salad.

Whole GrainsFoods we should include in our diet. I put these in a separate category because Dr. Strangelove and his colleagues have been telling us to eliminate them from our diet, and many Americans are following those recommendations:

  • Whole grains. We can think of whole grains as the underserving victim of the low-carb craze. The low-carb craze is on the mark when it comes to eliminating added sugars and refined grains from the diet. However, eliminating whole grains from the diet may be doing more harm than good. In fact, this and other studies suggest that whole grains are the most effective foods for reducing cancer risk. Why is that?
    • If we assume whole grains are just a good source of fiber and a few vitamins and minerals, it is hard to grasp their importance. We could easily get those nutrients elsewhere.
    • However, we are beginning to realize that whole grains play a unique role in supporting certain species of gut bacteria that are very beneficial to our health. In short, whole grains may be essential for a healthy gut.
  • Dairy Foods. This is another food that has been treated as a villain by Dr. Strangelove and his many colleagues. However, for reasons we don’t completely understand, dairy foods appear to decrease the risk of heart disease and cancer.

Foods we should balance in our diet.

  • Red Meat. Diets high in red meat are consistently associated with a slight increase in cancer risk. The World Health Organization lists red meat as a probable carcinogen, but that has proven to be controversial.
    • Much of the research has centered on why red meat causes cancer. Several mechanisms have been proposed, but none of them have been proven.
    • In contrast, very little consideration has been given to what red meat is displacing from the diet. Diets high in red meat are often low in whole grains, fruits and/or vegetables.
    • Perhaps instead of eliminating red meat from our diets we should be talking about balancing red meat in our diets by consuming less red meat and more whole grains, fruits, and vegetables.

What Can You Do To Reduce Cancer Risk?

American Cancer SocietyYou may have been thinking that 80,110 cases/year represents a small percentage of new cancer cases. That’s because diet is only one component of a holistic cancer prevention strategy. Here is what the American Cancer Society recommends for reducing cancer risk:

  • Avoid tobacco.
  • Limit sun exposure.
  • Achieve and maintain a healthy weight.
  • Eat a healthy diet, with an emphasis on plant foods (Their recommendations are in line with this study).
  • Be physically active.
  • Limit alcohol use.
  • Get vaccinated against HPV.
  • Get regular medical checkups.

Doing any of these things will reduce your cancer risk. But the more of these you can incorporate into your lifestyle, the lower your risk.

The Bottom Line

A recent study looked at diet and cancer risk. The authors reported that 80,110 new cancer cases among US adults 20 and older could be primarily attributed to poor diet.

When the diet was broken down into individual food groups:

  • Low intake of whole grains was associated with the largest number of preventable cancer cases. This was followed in descending order by.
  • Low intake of dairy foods.
  • High intake of processed meats.
  • Low intake of vegetables.
  • Low intake of fruits.
  • High intake of red meat.
  • High intake of sugar sweetened beverages.

The authors concluded: “More than 80,000 new cancer cases [per year] are estimated to be associated with suboptimal diet among US adults…Our findings underscore the need for reducing cancer burden in the United States by improving the intake of key food groups and nutrients of Americans.”

For more details, read the article above. For example, I discuss which foods we should eliminate, which foods we should eat more of, and which foods we should balance in our diet. To add a more holistic perspective, I also discuss the American Cancer Society’s recommendations for reducing cancer risk.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

Health Tips From The Professor