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.

 

Will Non-GMO Foods Be Less Nutritious?

The Unintended Consequences of the Proposed Non-GMO Labeling Laws

Author: Dr. Stephen Chaney

CerealPost Foods recently announced that their Grape Nuts cereal will be completely non-GMO. General Foods followed suit by announcing that their Original Cheerios will also be non-GMO. That’s good news, right?

Maybe, but it turns out that the new non-GMO Grape Nuts will no longer contain vitamins A, D, B12 or riboflavin, and the amount of riboflavin in a serving of Cheerios decreased from 25% of the daily recommended value (DV) to 2% of the DV.

The cereal manufacturers claim that their new cereals are more wholesome, but one nutrition expert said “The new products are arguably less healthy given their lower vitamin content.”

I’ve never been one to claim that throwing a few vitamins into a serving of cereal turns it into a nutrition powerhouse, but the decreased vitamin content of the new non-GMO cereals does raise a few questions.

  • Why were the vitamins removed?
  • Did it have anything to do with the cereals being non-GMO?
  • Does this mean that the non-GMO processed foods of the future will be less nutritious than the foods they replace?

The cereal manufacturers were mum when asked these questions, so we will need to rely on some scientific sleuthing and a bit of intuition to get the answers.

The Flaw in The Proposed Non-GMO Labeling Laws

I first discussed this topic a few months ago in a “Health Tips From The Professor” article titled “When is GMO Non-GMO?” I received a lot of irate comments from people who take every word on the non-GMO websites and videos as the gospel truth. (The professor has never been one to shy away from controversy when he sees claims that aren’t based on good science.)

However, I think my article was misunderstood by some of my readers, so let me review my conclusions briefly:

  • There are definitely environmental concerns around the widespread use of GM crops – especially those that allow heavy pesticide and herbicide usage.
  • There are potential health concerns related to the consumption of unprocessed GM foods and proteins derived from GM foods – although those heath concerns have been blown way out of proportion in the media.

If the proposed Non-GMO labeling laws stopped there, they would be scientifically justified. But they go one step further by requiring that processed foods labeled as non-GMO cannot contain any ingredient obtained from a GM source. There is no scientific justification for this.

  • Nutrients (sugars, oils & vitamins) derived from GM sources are chemically and biologically indistinguishable from those same nutrients derived from non-GMO sources.

The intentions of the proposed non-GMO labeling laws are good, but whenever you go beyond what good science supports there are often unintended consequences – such as the vitamin-depleted non-GMO cereals that the food manufacturers have just announced.

Will Non-GMO Foods Be Less Nutritious?

Non-GMOTo understand the answer to that question, let’s look at what probably happened to the vitamins in the non-GMO cereals.

In today’s world many vitamins are purified from genetically modified microorganisms – bacteria & yeast that have been modified to overproduce certain vitamins. In evaluating the significance of that statement, here are a few facts to consider:

1)     We have gotten vitamins from these sources for many years.

    • B vitamins have been obtained from yeast for at least a hundred years.
    • A significant portion of the vitamins we absorb on a daily basis are made by bacteria in our gut.

2)     The only difference today is that these microorganisms have been genetically modified to overproduce the vitamins.

3)     These are naturally sourced vitamins.

  • The microorganisms are the same ones that have provided these vitamins for generations.
  • The enzymes used by the microorganisms to make the vitamins are the same.

4)     There is no downside to the use of GM organisms as a source of natural vitamins.

    • There is no environmental risk from the use of these GM microorganisms. They don’t contain any dangerous genes that could wreak havoc if they escaped from the food processing plants.
    • Because the purified vitamins are indistinguishable from those obtained from non-GMO sources, there are also no health risks.

5)     The advantage of using these GM organisms is clear. It substantially lowers the cost of vitamins and allows them to be used in the mass market – for example, in popular breakfast cereals.

6)     Most food manufacturers can’t simply use non-GMO sourced vitamins and raise their prices.

    • A recent poll showed that 53% of Americans prefer non-GMO foods, but only 11% are willing to pay more for those foods

What Does the Future Hold?

Even though they are scientifically flawed, the proposed non-GMO labeling laws will probably become the law in several states in the near future. (Good science has never played much of a role in political decisions.)

Currently, there simply aren’t enough non-GMO vitamins available to supply the mass market – even if price were no concern. So, in the short term, many non-GMO processed foods are likely to be less nutritious than the foods they will replace – as we just saw with Grape Nuts and Cheerios.

However, most people feel that American ingenuity and the law of supply and demand will eventually result in a bigger supply of reasonable priced non-GMO vitamins. When that happens non-GMO processed foods will be just as nutritious as the older GM versions.

However, at this point nobody knows how long that will take.

The Bottom Line:

1)     There is a scientific basis for environmental and potential health concerns regarding genetically modified whole foods and the protein extracted from these foods.

2)     However, proposed non-GMO labeling laws would require that a processed food be labeled as genetically modified if it contains any nutrient purified from a genetically modified organism.

3)     There is no scientific justification for this requirement. Purified vitamins from GM and non-GM microorganisms are chemically and biologically indistinguishable. Furthermore, the GM microorganisms used to produce the vitamins pose no environmental or health risks.

4)     Non-GMO vitamins (vitamins prepared from non-GMO microorganisms) are currently in short supply and are very expensive compared to vitamins prepared from GM microorganisms.

5)     Consequently, the unintended consequence of these proposed non-GMO labeling laws will likely be that many of the new non-GMO processed foods will contain fewer vitamins and, therefore, will be less nutritious than the foods they replace – at least in the short term. The new non-GMO Grape Nuts and Cheerios may be just the tip of the iceberg.

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