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

Does Protein Supplement Timing Matter?

Posted May 15, 2018 by Dr. Steve Chaney

How Do You Gain Muscle Mass & Lose Fat Mass?

Author: Dr. Stephen Chaney

 

protein supplement timingMost of what you read about protein supplements on the internet is wrong. That is because most published studies on protein supplements:

  • Are very small
  • Are not double blinded.
    • Both the subjects and the investigators knew who got the protein supplement.
  • Are done by individual companies with their product.
    • You have no idea which ingredients are in their product are responsible for the effects they report.
    • You have no idea how their product compares with other protein products.
    • There is no standardization with respect to the amount or type of protein or the addition of non-protein ingredients.

Because of these limitations there is a lot of misleading information on the benefits of protein supplements timing and maximal benefit. Let’s start by looking at why people use protein supplements. Let’s also look at what is generally accepted as true with respect to the best supplement timing.

There are 4 major reasons people consume protein supplements:

  • Enhance the muscle gain associated with resistance training: In this case, protein supplements are customarily consumed concurrently with the workout.
  • Preserve muscle and accelerate fat loss while on a weight loss diet: In this case, protein supplements are customarily consumed with meals or as meal replacements.
  • Provide a healthier protein source. In this case, protein supplements are customarily consumed with meals in place of meat protein.
  • Prevent muscle loss associated with aging or illness. There is no customary pattern associated with this use of protein supplements.

How good are the data supporting the customary timing of protein supplementation? The answer is: Not very good. The timing is based on a collection of weak studies which do not always agree with each other.

The current study  (J.L. Hudson et al, Nutrition Reviews, 76: 461-468, 2018 ) was designed to fill this void in our knowledge. It is a meta-analysis that compares all reasonably good studies that have looked at the effect of protein supplement timing on weight gain or loss, lean muscle mass gain, fat loss, and the ratio of lean muscle mass to fat mass.

How Was The Study Done?

The authors started by doing a literature search of all studies that met the following criteria:

  • The study was a randomized control trial with parallel design. This means that study contained a control group. It does not mean that the investigators or subjects were blinded with respect to which subjects used a protein supplement and which did not.
  • The subjects were engaged in resistance training.
  • The study lasted 6 weeks or longer.
  • Reliable methods were used to measure body composition (lean muscle mass and fat mass).
  • The subjects were healthy and at least 19 years old.
  • There was no restriction on the food the subjects consumed.

The authors started with 2074 published studies and ended up with 34 that met all their criteria. They then separated the studies into two groups – those in which the protein supplements were used with meals and those in which the protein supplements were used between meals.

Both groups were diverse.

  • Group 1 included subjects who consumed their protein supplement with their meal and those who consumed their protein supplement as a meal replacement.
  • Group 2 included subjects who consumed their protein supplement concurrent with exercise (usually immediately after exercise) and those who consumed their protein supplement at a fixed time of day not associated with exercise.

Does Protein Supplement Timing Matter?

 

protein supplement timing workoutsBecause the individual studies were very diverse in the way they were designed, the authors could not calculate a reliable estimate of how much lean muscle mass was increased or fat mass was decreased. Instead, they calculated the percentage of studies showing an increase in lean muscle mass or a decrease in fat mass.

When the authors compared protein supplements consumed with meals versus protein supplements consumed between meals:

  • Weight gain was observed in 56% of the studies of protein supplementation with meals compared to 72% of the studies of protein supplementation between meals. In other words, protein supplements consumed with meals were less likely to lead to weight gain than protein supplements consumed between meals.
  • An increase in lean muscle mass was observed in 94% of the studies of protein supplementation with meals compared to 90% of the studies of protein supplementation between meals. In other words, timing of protein supplementation did not matter with respect to increase in muscle mass.
  • A loss of fat mass was observed in 87% of the studies of protein supplementation with meals compared to 59% of the studies of protein supplementation between meals. In other words, protein supplements consumed with meals were more likely to lead to loss of fat mass.
  • An increase in the ratio of lean muscle mass to fat mass was observed in 100% of the studies of protein supplementation with meals compared to 87% of the studies of protein supplementation between meals. In short, protein supplements consumed with meals were slightly more likely to lead to an increase in the ratio of lean muscle mass to fat mass.

The following seem to suggest protein supplement timing matters:

The authors pointed out that their findings were consistent with previous studies showing that when protein supplements are consumed with a meal they displace some of the calories that otherwise would have been consumed. Simply put, people naturally compensate by eating less of other foods.

In contrast, the authors stated that previous studies have shown that when foods, especially liquid foods, are consumed as snacks (between meals), people are less likely to compensate by reducing the calories consumed in the next meal.

The others concluded: “Concurrently with resistance training, consuming protein supplements with meals, rather than between meals, may more effectively promote weight control and reduce fat mass without influencing improvements in lean [muscle] mass.”

What Are The Limitations Of The Study?

Meta-analyses such as this one, are only as good as the studies included in the meta-analysis. Unfortunately, most sports nutrition studies are very weak studies. Thus, this meta-analysis is a perfect example of the “Garbage In: Garbage Out (GI:GO)” phenomenon.

For example, let’s start by looking at what the term “protein supplement” meant.

  • Because the studies were done by individual companies with their product, the protein supplements in this meta-analysis:
    • Included whey, casein, soy, bovine colostrum, rice or combinations of protein sources.
    • Were isolates, concentrates, or hydrolysates.
    • Contained various additions like creatine, amino acids, and carbohydrate.
  • As I discuss in my book, Slaying the Food Myths, previous studies have shown that optimal protein and leucine levels are needed to maximize the increase in muscle mass and decrease in fat mass associated with resistance exercise. However, neither protein nor leucine levels were standardized in the protein supplements included in this meta-analysis.
  • Previous studies have shown that protein supplements that have little effect on blood sugar levels (have a low glycemic index) are more likely to curb appetite. However, glycemic index was not standardized for the protein supplements included in this meta-analysis.

protein supplement timing workout peopleIn short, the conclusions of this study might be true for some protein supplements, but not for others. We have no way of knowing.

We also need to consider the composition of the two groups.

  • Protein supplements used as meal replacements are more likely to decrease weight and fat mass than protein supplements consumed with meals. Yet, both were included in group 1.
  • Some studies suggest that protein supplements consumed concurrent with resistance exercise are more likely to increase muscle mass than protein supplements consumed another time of day. Yet, both are included in group 2. We also have no idea whether the meals with protein supplements in group 1 were consumed shortly after exercise or at an entirely different time of day.

This was the most glaring weakness of the study because it was completely avoidable. The authors could have grouped the studies into categories that made more sense.

In other words, there are multiple weaknesses that limit the predictive power of this study.

What Can We Learn From This Study?

Despite its many limitations, this study does remind us that protein supplements do have calories. This is of relatively little importance for people whose primary goal is to increase lean muscle mass.

However, most of us are using protein supplements to lose weight or to increase our lean mass to fat mass ratio. Simply put, we are either trying to lean out (shape up) or lose weight. And, we want to lose that weight primarily by getting rid of excess fat. For us, calories do matter. With that in mind:

  • If we are consuming a protein supplement immediately after exercise or between meals we probably should make a conscious effort to reduce our daily caloric intake elsewhere in our diet.
  • Alternatively, we could consume the protein supplement with a meal, but time the meal so it occurs shortly after exercise.

 

The Bottom Line:

 

A recent study looked at the optimal timing of protein supplements consumed by subjects who were engaged in resistance exercise. Specifically, the study compared protein supplements consumed with meals versus protein supplements consumed between meals on weight, lean muscle mass, fat mass, and the ratio of lean muscle mass to fat mass. The study reported:

  • Protein supplements consumed with meals were less likely to lead to weight gain than protein supplements consumed between meals.
  • Timing of protein supplementation did not matter with respect to increase in muscle mass.
  • Protein supplements consumed with meals were more likely to lead to loss of fat mass.
  • Protein supplements consumed with meals were slightly more likely to lead to an increase in the ratio of lean mass to fat mass.

The authors pointed out that their findings were consistent with previous studies showing that when a protein supplement was consumed with a meal it displaces some of the calories that would have been otherwise consumed. Simply put, people naturally compensate by eating less of other foods.

In contrast, the authors said that previous studies have shown that when foods, especially liquid foods, are consumed as snacks (between meals), people are less likely to compensate by reducing the calories consumed in the next meal.

As discussed in the article above, the study has major weaknesses. However, despite its many weaknesses, this study does remind us that protein supplements do have calories. This is of relatively little importance for people whose primary goal is to increase lean muscle mass.

However, for those of us who are using protein supplements to lose weight or to increase our lean mass to fat mass ratio, calories do matter.  With that in mind:

  • If we are consuming a protein supplement immediately after exercise or between meals we probably should make a conscious effort to reduce our daily caloric intake elsewhere in our diet.
  • Alternatively, we could consume the protein supplement with a meal, but time the meal so it occurs shortly after exercise.

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.

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