Folic Acid and Cancer

Written by Dr. Steve Chaney on . Posted in Drugs and Health, Supplements and Health

Does Folic Acid Increase Cancer Risk?

Author: Dr. Stephen Chaney

 

folic acid and cancerYou’ve seen the headlines. “Folic Acid Supplements May Increase Colon Cancer Risk in People Over 50” and “Folic Acid Supplements May Increase Prostate Cancer Risk in Men”. And I’ve seen articles telling people over 50 that they should take their multivitamin tablets every other day to avoid getting too much folic acid.

I’ve even heard of doctors telling their patients to avoid any supplements containing folic acid. So what’s the truth?  Is there a cause and effect relationship between folic acid and cancer?

Why Do People Say Folic Acid Increases Colon Cancer Risk?

Perhaps a bit of historical perspective is in order. A number of population studies had suggested that high intakes of folic acid might protect against cancer, especially colon cancer, so several placebo controlled clinical studies were initiated to test that hypothesis. Those studies had mixed results, with some suggesting that folic acid might be protective and others suggesting that it had no effect. None of those studies suggested that folic acid supplementation increased the risk of any kind of cancer.

In 1998 mandatory folic acid fortification of grain products was introduced. In addition, the number of Americans taking supplements with folic has increased dramatically in recent years. As a consequence total intake of folates (folic acid from fortified foods and supplements plus folates naturally found in foods) has increased significantly. By one estimate blood levels of folates have increased 2.5-fold between 1994 (before fortification) and 2000 (after fortification).

So it was just natural to ask if this increase in folate intake might have unintended consequences. And one clinical study seemed to suggest that it might (JAMA, 297: 2351-2359, 2007)

That study looked at colorectal adenomas and reported high folate intake was associated with an increased risk of more advanced adenomas. [It is important to note that adenomas are benign tumors. They are thought to be precursors to colorectal cancer but they are not actually cancerous].

Some experts immediately started warning about getting too much folic acid in the diet – with some going so far as to warn that people over 50 should only take a multivitamin every other day.

And several papers were published speculating on how differences between the way that folic acid and the other folates were utilized by the body could cause folic acid to increase the risk of colorectal cancer while naturally occurring folates decreased the risk.

Let me put this into perspective. Any good scientist knows not to trust a single clinical study. Individual clinical studies can provide misleading results. Sometimes it is possible to pinpoint the cause. For example, the study may have been poorly designed, may have included a non-representative population group, or the statistical analysis may have been incorrect. But, sometimes we never know why an individual clinical study came to the wrong conclusion.

folic acid and colon cancerThat is why good scientists generally say that more studies are needed and base their recommendation on the preponderance of many studies rather than a single study.

The problem was that all of this hype and hypothesizing about folic acid increasing the risk of colon cancer was based on a single study, and that study didn’t actually look at colorectal cancer. A Norwegian study four years later found no evidence for increased colorectal cancer at folic acid intakes of up to 800 ug/day (AJCN, 94: 1053-1062, 2011) – but it was largely ignored.

The background is similar for the claims that folic acid may increase prostate cancer risk. When a small meta-analysis that included some, but not all, published clinical studies suggested an increased risk of prostate cancer, some experts went as far as to suggest that men should completely avoid supplements with folic acid.

The problem is that even meta-analyses can be misleading if they only examine a small sub-set of clinical studies because they can be unduly influenced by a single misleading clinical study.

Does Folic Acid Increase Colon Cancer Risk?

Should We Avoid Supplemental Folate?

The American Cancer Society decided to resolve the uncertainty about folic acid intake and colon cancer risk once and for all (V.L. Stevens et al, Gastroenterology, 141: 98-105, 2011). They designed the study to answer two very important questions:

1) Has the increased folate intake by Americans over the past several years actually increased their risk for colorectal cancer?

2) Does the chemical form (folic acid versus folate) influence its effect on colorectal cancer risk?

And this study had two very important firsts:

1) This was the very first study to investigate the association between folate intake and colorectal cancer entirely in the post-fortification period.

2) This was also the very first study to separate out the effects of folate and folic acid on colorectal cancer risk.

And it was a very large study. They followed 43,512 men and 56,011 women aged 50-74 for 8 years between 1999 and 2007.

Folate intakes from food ranged from 175 ug/day to 354 ug/day while folic acid intakes from food fortification, supplements and multivitamins ranged from 71 ug/day to 660 ug/day. Total folate (both naturally occurring folates and folic acid) intakes ranged from 246 ug/day to over 1014 ug/day.

When they analyzed the data they found that high intakes of neither folic acid nor natural folates were associated with any increased risk of colorectal cancer. In fact, they found high intake of total folates was associated with a significant decreased risk of colorectal cancer.

Does Folic Acid Increase Cancer Risk?

folates help prevent cancerWhat about prostate cancer and other types of cancer? Could folic acid increase the risk of other cancers? To resolve this issue once and for all, a group from Oxford University (Clarke et al, The Lancet, doi: 10.1016/S0140-6736(12)62001-7) did a meta-analysis of every study published through 2010 that compared folic acid supplementation to a placebo, lasted at least 1 year, included at least 500 people and recorded cancer incidence – some 13 studies with over 50,000 participants.

The results were clear cut. As for folic acid and cancer, supplementation did not increase the overall cancer risk, and when the incidence of individual cancers was analyzed, folic acid supplementation did not increase the risk of developing colon cancer, prostate cancer, lung cancer, breast cancer or any other site-specific cancer.

To put this in perspective the average dose of folic acid used in these clinical studies was 2 mg/day, which is 5 times the RDA and 5 times the dose in most supplements. And one of the clinical trials used 40 mg/day, which is 100 times the dose in most supplements.

 

The Bottom Line

Forget the warnings and the hype. You can be confident that folic acid does not increase the risk of colorectal cancer, prostate cancer, or any other kind of cancer.

  • The American Cancer Society recently performed a very large clinical study looking at the effect of folic acid intake from supplements and folate intake from foods on colon cancer risk. That study found that high intakes of neither folic acid nor natural folates were associated with any increased risk of colorectal cancer. And, they found high intake of total folates was associated with a significant decreased risk of colorectal cancer.
  • The authors of that study concluded: “The findings of this study add to the epidemiological evidence that high folate intake reduces colorectal cancer risk.” “More importantly, no increased risk of colorectal cancer was found, suggesting that the high levels of this vitamin consumed by significant numbers of Americans should not lead to higher incidence rates of this cancer in the population.”
  • A second meta-analysis of every clinical study looking at folic acid intake and cancer risk through 2010. The results of that study were clear cut. Folic acid supplementation did not increase the overall cancer risk, and when the incidence of individual cancers was analyzed, folic acid supplementation did not increase the risk of developing colon cancer, prostate cancer, lung cancer, breast cancer or any other site-specific cancer

Like any good scientist I am aware that future studies could change our understanding, but for now I am confident in saying that there is no credible evidence that folic acid supplementation increases your risk of any kind of cancer. If the science changes, I will be the first to let you know.

But it will be really interesting to see how long it takes all those web sites, blogs and so-called “experts” to acknowledge that the science has changed and they should stop issuing false warnings about folic acid supplementation.

 

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.

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Latest Article

Can Plant-based Diets Be Unhealthy?

Posted September 10, 2019 by Dr. Steve Chaney

Do Plant-Based Diets Reduce Heart Disease Deaths?

Author: Dr. Stephen Chaney

 

plant-based diets vegetablesPlant-based diets have become the “Golden Boys” of the diet world. They are the diets most often recommended by knowledgeable health and nutrition professionals. I’m not talking about all the “Dr. Strangeloves” who pitch weird diets in books and the internet. I am talking legitimate experts who have spent their life studying the impact of nutrition on our health.

Certainly, there is an overwhelming body of evidence supporting the claim that plant-based diets are healthy. Going on a plant-based diet can help you lower blood pressure, inflammation, cholesterol and triglycerides. People who consume a plant-based diet for a lifetime weigh less and have decreased risk of heart disease, diabetes, and cancer.

But, can a plant-based diet be unhealthy? Some people consider a plant-based diet to simply be the absence of meat and other animal foods. Is just replacing animal foods with plant-based foods enough to make a diet healthy?

Maybe not. After all, sugar and white flour are plant-based food ingredients. Fake meats of all kinds abound in our grocery stores. Some are very wholesome, but others are little more than vegetarian junk food. If you replace animal foods with plant-based sweets, desserts, and junk food, is your diet really healthier?

While the answer to that question seems obvious, very few studies have asked that question. Most studies on the benefits of plant-based diets have compared population groups that eat a strictly plant-based diet (Seventh-Day Adventists, vegans, or vegetarians) with the general public. They have not looked at variations in plant food consumption within the general public. Nor have they compared people who consume healthy and unhealthy plant foods.

This study (H Kim et al, Journal of the American Heart Association, 8:e012865, 2019) was designed to fill that void.

 

How Was The Study Done?

plant-based diets studyThis study used data collected from 12,168 middle aged adults in the ARIC (Atherosclerosis Risk in Communities) study between 1987 and 2016.

The participant’s usual intake of foods and beverages was assessed by trained interviewers using a food frequency questionnaire at the time of entry into the study and again 6 years later.

Participants were asked to indicate the frequency with which they consumed 66 foods and beverages of a defined serving size in the previous year. Visual guides were provided to help participants estimate portion sizes.

The participant’s adherence to a plant-based diet was assessed using four different well-established plant-based diet scores. For the sake of simplicity, I will include 3 of them in this review.

  • The PDI (Plant-Based Diet Index) categorizes foods as either plant foods or animal foods. A high PDI score means that the participant’s diet contains more plant foods than animal foods. A low PDI score means the participant’s diet contains more animal foods than plant foods.
  • The hPDI (healthy plant-based diet index) is based on the PDI but emphasizes “healthy” plant foods. A high hPDI score means that the participant’s diet is high in healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, coffee and tea) and low in animal foods.
  • The uPDI (unhealthy plant-based diet index) is based on the PDI but emphasizes “unhealthy” plant foods. A high uPDI score means that the participant’s diet is high in unhealthy plant foods (refined grains, fruit juices, French fries and chips, sugar sweetened and artificially sweetened beverages, sweets and desserts) and low in animal foods.

For statistical analysis the scores from the various plant-based diet indices were divided into 5 equal groups. In each case, the group with the highest score consumed the most plant foods and least animal foods. The group with the lowest score consumed the least plant foods and the most animal foods.

The health outcomes measured in this study were heart disease events, heart disease deaths, and all-cause deaths. Again, for the sake of simplicity, I will only include 2 of these outcomes (heart disease deaths and all-cause deaths) in this review. The data on deaths were obtained from state death records and the National Death Index. (Yes, your personal information is available on the web even after you die.)

 

Do Plant-Based Diets Reduce Heart Disease Deaths?

plant-based diets reduce heart deathsThe participants in this study were followed for an average of 25 years.

The investigators looked at heart disease deaths over the 25 years and compared people with the highest intake of plant foods to people with the highest intake of red meat and other animal foods. The results were:

  • People with the highest intake of plant foods and the highest intake of healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, coffee and tea) had a 19-32% lower risk of dying from heart disease than people with the highest intake of red meat and other animal foods.
  • People with the highest intake of unhealthy plant foods (refined grains, fruit juices, French fries and chips, sugar sweetened and artificially sweetened beverages, sweets and desserts) had the same risk of dying from heart disease as people with the highest intake of red meat and other animal foods.

When the investigators looked at all-cause deaths over the 25 years:

  • People with the highest intake of plant foods and the highest intake of healthy plant foods had an 11-25% lower risk of dying from any cause than people with the highest intake of red meat and other animal foods.
  • People with the highest intake of unhealthy plant foods had the same risk of dying from heart disease as people with the highest intake of red meat and other animal foods.

What Else Did The Study Show?

The investigators made a couple of other interesting observations:

  • The association of the overall diet with heart disease and all-cause deaths was stronger than the association of individual food components. This underscores the importance of looking at the effect of the whole diet on health outcomes rather than the “magic” foods you hear about on Dr. Strangelove’s Health Blog.
  • Diets with the highest amount of healthy plant foods were associated with higher intake of carbohydrates, plant protein, fiber, and micronutrients, including potassium, magnesium, iron, vitamin A, vitamin C, folate, and lower intake of saturated fat and cholesterol.
  • Diets with the highest amount of unhealthy plant foods were associated with higher intake of calories and carbohydrates and lower intake of fiber and micronutrients.

The last two observations may help explain some of the health benefits of plant-based diets.

 

Can Plant-Based Diets Be Unhealthy?

plant-based diets unhealthy cookiesNow, let’s return to the question I asked at the beginning of this article: “Can plant-based diets be unhealthy?” Although some previous studies have suggested that unhealthy plant-based diets might increase the risk of heart disease, this study did not show that.

What this study did show was that an unhealthy plant-based diet was no better for you than a diet containing lots of red meat and other animal foods.

If this were the only conclusion from this study, it might be considered a neutral result. However, this result clearly contrasts with the data from this study and many others showing that both plant-based diets in general and healthy plant-based diets reduce the risk of heart disease deaths and all-cause deaths compared to animal-based diets.

The main message from this study is clear.

  • Replacing red meat and other animal foods with plant foods can be a healthier choice, but only if they are whole, minimally processed plant foods like whole grains, fruits, vegetables, nuts, legumes, coffee and tea.
  • If the plant foods are refined grains, fruit juices, French fries and chips, sugar sweetened and artificially sweetened beverages, sweets and desserts, all bets are off. You may be just as unhealthy as if you kept eating a diet high in red meat and other animal foods.

There is one other subtle message from this study. This study did not compare vegans with the general public. Everyone in the study was the general public. Nobody in the study was consuming a 100% plant-based diet.

For example:

  • The group with the highest intake of plant foods consumed 9 servings per day of plant foods and 3.6 servings per day of animal foods.
  • The group with the lowest intake of plant foods consumed 5.4 servings per day of plant foods and 5.6 servings per day of animal foods.

In other words, you don’t need to be a vegan purist to experience health benefits from adding more whole, minimally processed plant foods to your diet.

 

The Bottom Line

A recent study analyzed the effect of consuming plant foods on heart disease deaths and all-cause deaths over a 25-year period.

When the investigators looked at heart disease deaths over the 25 years:

  • People with the highest intake of plant foods and the highest intake of healthy plant foods had a 19-32% lower risk of dying from heart disease than people with the highest intake of red meat and other animal foods.
  • People with the highest intake of unhealthy plant foods had the same risk of dying from heart disease as people with the highest intake of red meat and other animal foods.

When the investigators looked at all-cause deaths over the 25 years:

  • People with the highest intake of plant foods and the highest intake of healthy plant foods had an 11-25% lower risk of dying from any cause than people with the highest intake of red meat and other animal foods.
  • People with the highest intake of unhealthy plant foods had the same risk of dying from heart disease as people with the highest intake of red meat and other animal foods.

The main message from this study is clear.

  • Replacing red meat and other animal foods with plant foods can be a healthier choice, but only if they are whole, minimally processed plant foods like whole grains, fruits, vegetables, nuts, legumes, coffee and tea.
  • If the plant foods are refined grains, fruit juices, French fries and chips, sugar sweetened and artificially sweetened beverages, sweets and desserts, all bets are off. You may be just as unhealthy as if you kept eating a diet high in red meat and other animal foods.

A more subtle message from the study is that you don’t need to be a vegan purist to experience health benefits from adding more whole, minimally processed plant foods to your diet. The people in this study were not following some special diet. The only difference was that some of the people in this study ate more plant foods and others more animal foods.

For more details on the study, 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.

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