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.

Trackback from your site.

Leave a comment

Recent Videos From Dr. Steve Chaney

READ THE ARTICLE
READ THE ARTICLE

Latest Article

Do Omega-3s Lower Blood Pressure in Young, Healthy Adults?

Posted August 14, 2018 by Dr. Steve Chaney

What Is The Omega-3 Index And Why Is It Important?

Author: Dr. Stephen Chaney

 

Do omega-3s lower blood pressure in healthy adults?

omega-3s lower blood pressure young adultsThe literature on the potential health benefits of omega-3s is very confusing. That’s because a lot of bad studies have been published. Many of them never determined the omega-3 status of their subjects prior to omega-3 supplementation. Others relied on dietary recalls of fish consumption, which can be inaccurate.

Fortunately, a much more accurate measure of omega-3 status has been developed and validated in recent years. It’s called the Omega-3 Index. Simply put, the Omega-3 Index is the percentage of EPA and DHA compared to 26 other fatty acids found in cellular membranes. Using modern technology, it can be determined from a single finger prick blood sample. It is a very accurate reflection of omega-3 intake relative to other fats in the diet over the past few months. More importantly, it is a measure of the omega-3 content of your cell membranes, which is a direct measure of your omega-3 nutritional status.

A recent extension of the Framingham Heart Study reported that participants with an Omega-3 Index >6.8% had a 39% lower risk of cardiovascular disease than those with an Omega-3 Index <4.2% (WS Harris et al, Journal of Clinical Lipidology, 12: 718-724, 2018 ). Although more work needs to be done, an Omega-3 Index of 4% or less is generally considered indicative of high cardiovascular risk, while 8% or better is considered indicative of low cardiovascular risk. For reference, the average American has an Omega-3 Index in the 4-5% range. In Japan, where fish consumption is much higher and cardiovascular risk much lower, the Omega-3 Index is in the 9-11% range.

Previous studies have suggested that omega-3 fatty acids lower blood pressure to a modest extent. Thus, it is not surprising that more recent studies have shown an inverse correlation between Omega-3 Index and blood pressure. However, those studies have been done with older populations, many of whom had already developed high blood pressure.

From a public health point of view, it is much more interesting to investigate whether it might be possible to prevent high blood pressure in older adults by optimizing omega-3 intake in a young, healthy population, most of whom had not yet developed high blood pressure. Unfortunately, there were no studies looking at that population. The current study was designed to fill that gap.

 

How Was The Study Done?

omega-3s lower blood pressure young healthy adultsThe current study (M.G. Filipovic et al, Journal of Hypertension, 36: 1548-1554, 2018 ) was based on data collected from 2036 healthy adults, aged 25-41, from Liechtenstein. They were participants in the GAPP (Genetic and Phenotypic Determinants of Blood Pressure) study. Participants were excluded from the study if they had been diagnosed with high blood pressure and were taking medication to lower their blood pressure. They were also excluded if they had heart disease, chronic kidney disease, other severe illnesses, obesity, sleep apnea, or daily use of non-steroidal anti-inflammatory medications.

Blood samples were collected at the time of their enrollment in the study and frozen for subsequent determination of Omega-3 Index. Blood pressure was also measured at their time of enrollment in two different ways. The first was a standard blood pressure measurement in a doctor’s office.

For the second measurement they were given a wearable blood pressure monitor that recorded their blood pressure over 24 hours every 15 minutes during the day and every 30 minutes while they were sleeping. This is considered more accurate than a resting blood pressure measurement in a doctor’s office because it records the variation in blood pressure, while you are sleeping, while you are exercising, and while you go about your everyday activities.

 

Do Omega-3s Lower Blood Pressure In Young, Healthy Adults?

omega-3s lower blood pressure young adults equipmentNone of the participants in the study had significantly elevated blood pressure. The mean systolic and diastolic office blood pressures were 120±13 and 78±9 respectively. The average Omega-3 Index in this population was 4.6%, which is similar to the average Omega-3 Index in the United States.

When they compared the group with the highest Omega-3 Index (average = 5.8%) with the group with the lowest Omega-3 Index (average = 4.6%):

  • The office measurement of systolic and diastolic blood pressure was decreased by 3.3% and 2.6% respectively
  • While those numbers appear small, the differences were highly significant.
  • The 24-hour blood pressure measurements showed a similar decrease.
  • Blood pressure measurements decreased linearly with increasing Omega-3 Index. [In studies of this kind, a linear dose-response is considered an internal validation of the differences observed between the group with the highest Omega-3 Index and the group with the lowest Omega-3 Index.]

The authors concluded: “A higher Omega-3 Index is associated with statistically significant, clinically relevant, lower systolic and diastolic blood pressure in normotensive, young and healthy individuals. Diets rich omega-3 fatty acids may be a strategy for primary prevention of hypertension.”

 

What Does This Mean For You?

omega-3s lower blood pressure young adults questionPerhaps I should first comment on the significance of the relatively small decrease in blood pressure observed in this study.

  • These were young adults, all of whom had normal or near normal blood pressure.
  • The difference in Omega-3 Index was rather small (5.8% to 4.6%). None of the participants in the study were at the 8% or above that is considered optimal.
  • Liechtenstein is a small country located between Switzerland and Spain. Fish consumption is low and omega-3 supplement consumption is rare.

Under these conditions, even a small, but statistically significant, decrease in blood pressure is remarkable.

We should think of this study as the start of the investigation of the relationship between omega-3 status and blood pressure. Its weakness is that it only shows an association between high Omega-3 Index and low blood pressure. It does not prove cause and effect.

Its strength is that it is consistent with many other studies showing omega-3 fatty acids lower blood pressure. Furthermore, it suggests that the effect of omega-3s on blood pressure may also be seen in young, healthy adults who have not yet developed high blood pressure.

Finally, the authors suggested that a diet rich in omega-3s might reduce the incidence of high blood pressure by slowing the age-related increase in blood pressure that most Americans experience. This idea is logical, but speculative at present.

However, the GAPP study is designed to provide the answer to that question. It is a long-term study with follow-up examinations scheduled every 3-5 years. It will be interesting to see whether the author’s prediction holds true, and a higher Omega-3 Index is associated with a slower increase in blood pressure as the participants age.

 

Why Is The Omega-3 Index Important?

 

The authors of this study said: “The Omega-3 Index is very robust to short-term intake of omega-3 fatty acids and reliably reflects an individual’s long-term omega-3 status and tissue omega-3 content. Therefore, the Omega-3 Index has the potential to become a cardiovascular risk factor as much as the HbA1c is for people with diabetes…” That is a bit of an overstatement. HbA1c is a measure of disease progression for diabetes because it is a direct measure of blood sugar control.

In contrast, Omega-3 Index is merely a risk factor for cardiovascular disease. However, if it is further validated by future studies, it is likely to be as important for predicting cardiovascular risk as are cholesterol levels and markers of inflammation.

However, to me the most important role of Omega-3 Index is in the design of future clinical studies. If anyone really wants to determine whether omega-3 supplementation reduces cardiovascular risk, high blood pressure, diabetes or any other health outcome they should:

  • Start with a population group with an Omega-3 Index in the deficient (4-5%) range.
  • Supplement with omega-3 fatty acids in a double blind, placebo-controlled manner.
  • Show that supplementation brought participants up to an optimal Omega-3 Index of 8% or greater.
  • Look at health outcomes such as heart attacks, cardiovascular deaths, hypertension, stroke, or depression.
  • Continue the study long enough for the beneficial effects of omega-3 supplementation to be measurable. For cardiovascular outcomes the American Heart Association has stated that at least two years are required to obtain meaningful results.

These are the kind of experiments that will be required to give definitive, reproducible results and resolve the confusion about the health effects of omega-3 fatty acids.

 

The Bottom Line

 

An accurate measure of omega-3 status has been developed and validated in recent years. It’s called the Omega-3 Index. Simply put, the Omega-3 Index is the percentage of EPA and DHA compared to 26 other fatty acids found in cellular membranes.

Although more work needs to be done, an Omega-3 Index of 4% or less is generally considered indicative of high cardiovascular risk while 8% or better is considered indicative of low cardiovascular risk.

Previous studies have shown an inverse correlation between Omega-3 Index and blood pressure. However, these studies have been done with older populations, many of whom had already developed high blood pressure.

From a public health point of view, it is much more interesting to investigate whether it might be possible to prevent high blood pressure in older adults by optimizing omega-3 intake in a young, healthy population, most of whom had not yet developed high blood pressure. Until now, there have been no studies looking at that population.

The study described in this article was designed to fill that gap. The participants in this study were ages 25-41, were healthy, and none of them had elevated blood pressure.

When the group with the highest Omega-3 Index (average = 5.8%) was compared with the group with the lowest Omega-3 Index (average = 4.6%):

  • Both systolic and diastolic blood pressure were decreased
  • Blood pressure measurements decreased linearly with increasing Omega-3 Index.

The authors concluded: “A higher Omega-3 Index is associated with statistically significant, clinically relevant, lower systolic and diastolic blood pressure in normotensive, young and healthy individuals. Diets rich omega-3 fatty acids may be a strategy for primary prevention of hypertension.”

Let me translate that last sentence into plain English for you. The authors were saying that optimizing omega-3 intake in young adults may slow the age-related increase in blood pressure and reduce the risk of them developing high blood pressure as they age. This may begin to answer the question “Do omega-3s lower blood pressure in young, healthy adults?”

Or even more simply put: Aging is inevitable. Becoming unhealthy is not.

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.

UA-43257393-1