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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Does Magnesium Optimize Vitamin D Levels?

Posted February 12, 2019 by Dr. Steve Chaney

The Case For Holistic Supplementation

Author: Dr. Stephen Chaney

 

Does magnesium optimize vitamin D levels?

magnesium optimize vitamin dOne of the great mysteries about vitamin D is the lack of correlation between vitamin D intake and blood levels of its active metabolite, 25-hydroxyvitamin D. Many people who consume RDA levels of vitamin D from foods and/or supplements end up with low blood levels of 25-hydroxyvitamin D. The reason(s) for this discrepancy between intake of vitamin D and blood levels of its active metabolite are not currently understood.

Another great mystery is why it has been so difficult to demonstrate benefits of vitamin D supplementation. Association studies show a strong correlation between optimal 25-hydroxyvitamin D levels and reduced risk of heart disease, cancer, and other diseases. However, placebo-controlled clinical trials of vitamin D supplementation have often come up empty. Until recently, many of those studies did not measure 25-hydroxyvitamin D levels. Could it be that optimal levels of 25-hydroxyvitamin D were not achieved?

The authors of the current study hypothesized that optimal magnesium status might be required for vitamin D conversion to its active form. You are probably wondering why magnesium would influence vitamin D metabolism. I had the same question.

The authors pointed out that:

  • Magnesium status affects the activities of enzymes involved in both the synthesis and degradation of 25-hydroxyvitamin D.
  • Some clinical studies have suggested that magnesium intake interacts with vitamin D intake in affecting health outcomes.
  • If the author’s hypothesis is correct, it is a concern because magnesium deficiency is prevalent in this country. In their “Fact Sheet For Health Professionals,” the NIH states that “…a majority of Americans of all ages ingest less magnesium from food than their respective EARs [Estimated Average Requirement]; adult men aged 71 years and older and adolescent females are most likely to have low intakes.” Other sources have indicated that magnesium deficiency may approach 70-80% for adults over 70.

If the author’s hypothesis that magnesium is required for vitamin D activation is correct and most Americans are deficient in magnesium, this raises some troubling questions.

  • Most vitamin D supplements do not contain magnesium. If people aren’t getting supplemental magnesium from another source, they may not be optimally utilizing the vitamin D in the supplements.
  • Most clinical studies involving vitamin D do not also include magnesium. If most of the study participants are deficient in magnesium, it might explain why it has been so difficult to show benefits from vitamin D supplementation.

Thus the authors devised a study (Q Dai et al, American Journal of Clinical Nutrition, 108: 1249-1258, 2018 ) to directly test their hypothesis.

 

How Was The Study Designed?

magnesium optimize vitamin d studyThe authors recruited 180 volunteers, aged 40-85, from an ongoing study on the prevention of colon cancer being conducted at Vanderbilt University. The duration of the study was 12 weeks. Blood was drawn at the beginning of the study to measure baseline 25-hydroxyvitamin D levels. Three additional blood draws to determine 25-hydroxyvitamin D levels were performed at weeks 1, 6, and 12.

Because high blood calcium levels increase excretion of magnesium, the authors individualized magnesium intake based on “optimizing” the calcium to magnesium ratio in the diet rather than giving everyone the same amount of magnesium. The dietary calcium to magnesium ratio for most Americans is 2.6 to 1 or higher. Based on their previous work, they considered an “ideal” calcium to magnesium ratio to be 2.3 to 1. The mean daily dose of magnesium supplementation in this study was 205 mg, with a range from 77 to 390 mg to achieve the “ideal” calcium to magnesium ratio. The placebo was an identical gel capsule containing microcrystalline cellulose.

Two 24-hour dietary recalls were conducted at baseline to determine baseline dietary intake of calcium and magnesium. Four additional 24-hour dietary recalls were performed during the 12-week study to assure that calcium intake was unchanged and the calcium to magnesium ratio of 2.3 to 1 was achieved.

In short this was a small study, but it was very well designed to test the author’s hypothesis.

 

Does Magnesium Optimize Vitamin D Levels?

 

does magnesium optimize vitamin d levelsThis was a very complex study, so I am simplifying it for this discussion. For full details, I refer you to the journal article (Q Dai et al, American Journal of Clinical Nutrition, 108: 1249-1258, 2018).

The most significant finding was that magnesium supplementation did affect blood levels of 25-hydroxyvitamin D. However, the effect of magnesium supplementation varied depending on the baseline 25-hydroxyvitamin D level at the beginning of the study.

  • When the baseline 25-hydroxyvitamin D was 20 ng/ml or less (which the NIH considers inadequate), magnesium supplementation had no effect on 25-hydroxyvitamin D levels.
  • When the baseline 25-hydroxyvitamin D was 20-30 ng/ml (which the NIH considers the lower end of the adequate range), magnesium supplementation increased 25-hydroxyvitamin D levels.
  • When the baseline 25-hydroxyvitamin D level approached 50 ng/ml (which the NIH says may be “associated with adverse effects”), magnesium supplementation lowered 25-hydroxyvitamin D levels.

The simplest interpretation of these results is:

  • When vitamin D intake is inadequate, magnesium cannot magically create 25-hydroxyvitamin D from thin air.
  • When vitamin D intake is adequate, magnesium can enhance the conversion of vitamin D to 25-hydroxyvitamin D.
  • When vitamin D intake is too high, magnesium can help protect you by lowering 25-hydroxyvitamin D levels.

The authors concluded: “Our findings suggest that optimal magnesium status may be important for optimizing 25-hydroxyvitamin D status. Further dosing studies are warranted…”

 

What Does This Study Mean For You?

magnesium optimize vitamin d for youThis was a groundbreaking study that has provided novel and interesting results.

  • It provides the first evidence that optimal magnesium status may be required for optimizing the conversion of vitamin D to 25-hydroxyvitamin D.
  • It suggests that optimal magnesium status can help normalize 25-hydroxyvitamin D levels by increasing low levels and decreasing high levels.

However, this was a small study and, like any groundbreaking study, has significant limitations. For a complete discussion of the limitations and strengths of this study I refer you to the editorial (S Lin and Q Liu, American Journal of Clinical Nutrition, 108: 1159-1161, 2018) that accompanied the study.

In summary, this study needs to be replicated by larger clinical studies with a more diverse study population. In order to provide meaningful results, those studies would need to carefully control and monitor calcium, magnesium, and vitamin D intake. There is also a need for mechanistic studies to better understand how magnesium can both increase low 25-hydroxyvitamin D levels and decrease high 25-hydroxyvitamin D levels.

However, assuming the conclusions of this study to be true, it has some interesting implications:

  • If you are taking a vitamin D supplement, you should probably make sure that you are also getting the DV (400 mg) of magnesium from diet plus supplementation.
  • If you are taking a calcium supplement, you should check that it also provides a significant amount of magnesium. If not, change supplements or make sure that you get the DV for magnesium elsewhere.
  • I am suggesting that you shoot for the DV (400 mg) of magnesium rather than reading every label and calculating the calcium to magnesium ratio. The “ideal” ratio of 2.3 to 1 is hypothetical at this point. A supplement providing the DV of both calcium and magnesium would have a calcium to magnesium ratio of 2.5, and I would not fault any manufacturer for providing you with the DV of both nutrients.
  • If you are taking high amounts of calcium, I would recommend a supplement that has a calcium to magnesium ratio of 2.5 or less.
  • If you are considering a magnesium supplement to optimize your magnesium status, you should be aware that magnesium can cause gas, bloating, and diarrhea. I would recommend a sustained release magnesium supplement.
  • Finally, whole grains and legumes are among your best dietary sources of magnesium. Forget those diets that tell you to eliminate whole food groups. They are likely to leave you magnesium-deficient.

Even if the conclusions of this study are not confirmed by subsequent studies, we need to remember that magnesium is an essential nutrient with many health benefits and that most Americans do not get enough magnesium in their diet. The recommendations I have made for optimizing magnesium status are common-sense recommendations that apply to all of us.

 

The Case For Holistic Supplementation

 

magnesium optimize vitamin d case for holistic supplementationThis study is one of many examples showing that a holistic approach to supplementation is superior to a “magic bullet” approach where you take individual nutrients to solve individual problems. For example, in the case of magnesium and vitamin D:

  • If you asked most nutrition experts and supplement manufacturers whether it is important to provide magnesium along with vitamin D, their answer would likely be “No”. Even if they are focused on bone health, they would be more likely to recommend calcium along with vitamin D than magnesium along with vitamin D.
  • If your doctor has tested your 25-hydroxyvitamin D levels and recommended a vitamin D supplement, chances are they didn’t also recommend that you optimize your magnesium status.
  • Clinical studies investigating the benefits of vitamin D supplementation never ask whether magnesium intake is optimal.

That’s because most doctors and nutrition experts still think of nutrients as “magic bullets.” I cover holistic supplementation in detail in my book “Slaying The Supplement Myths.”  Other examples that make a case for holistic supplementation that I cover in my book include:

  • A study showing that omega-3 fatty acids and B vitamins may work together to prevent cognitive decline. Unfortunately, most studies looking at the effect of B vitamins on cognitive decline have not considered omega-3 status and vice versa. No wonder those studies have produced inconsistent results.
  • Studies looking at the effect of calcium supplementation on loss of bone density in the elderly have often failed to include vitamin D, magnesium, and other nutrients that are needed for building healthy bone. They have also failed to include exercise, which is essential for building healthy bone. No wonder some of those studies have failed to find an effect of calcium supplementation on bone density.
  • A study reported that selenium and vitamin E by themselves might increase prostate cancer risk. Those were the headlines you might have seen. The same study showed Vitamin E and selenium together did not increase prostate cancer risk. Somehow that part of the study was never mentioned.
  • A study reported that high levels of individual B vitamins increased mortality slightly. Those were the headlines you might have seen. The same study showed that when the same B vitamins were combined in a B complex supplement, mortality decreased. Somehow that observation never made the headlines.
  • A 20-year study reported that a holistic approach to supplementation produced significantly better health outcomes.

In summary, vitamins and minerals interact with each other to produce health benefits in our bodies. Some of those interactions we know about. Others we are still learning about. When we take high doses of individual vitamins and minerals, we create potential problems.

  • We may not get the full benefit of the vitamin or mineral we are taking because some other important nutrient(s) may be missing from our diet.
  • Even worse, high doses of one vitamin or mineral may interfere with the absorption or enhance the excretion of another vitamin or mineral. That can create deficiencies.

The same principles apply to our diet. I mentioned earlier that whole grains and legumes are among the best dietary sources of magnesium. Eliminating those two foods from the diet increases our risk of becoming magnesium deficient. And, that’s just the tip of the iceberg. Any time you eliminate foods or food groups from the diet, you run the risk of creating deficiencies of nutrients, phytonutrients, specific types of fiber, and the healthy gut bacteria that use that fiber as their preferred food source.

The Bottom Line

 

A recent study suggests that optimal magnesium status may be important for optimizing 25-hydroxyvitamin D status. This is one of many examples showing that a holistic approach to supplementation is superior to a “magic bullet” approach where you take individual nutrients to solve individual problems. For example, in the case of magnesium and vitamin D:

  • If you asked most nutrition experts and supplement manufacturers whether it is important to provide magnesium along with vitamin D, their answer would likely be “No.”  Even if they are focused on bone health, they would be more likely to recommend calcium along with vitamin D than magnesium along with vitamin D.
  • If your doctor has tested your 25-hydroxyvitamin D levels and recommended a vitamin D supplement, chances are he or she did not also recommend that you optimize your magnesium status.
  • Clinical studies investigating the benefits of vitamin D supplementation never ask whether magnesium intake is optimal. That may be why so many of those studies have failed to find any benefit of vitamin D supplementation.

I cover holistic supplementation in detail in my book “Slaying The Supplement Myths” and provide several other examples where a holistic approach to supplementation is superior to taking individual supplements.

In summary, vitamins and minerals interact with each other to produce health benefits in our bodies. Some of those interactions we know about. Others we are still learning about. Whenever we take high doses of individual vitamins and minerals, we create potential problems.

  • We may not get the full benefit of the vitamin or mineral we are taking because some other important nutrient(s) may be missing from our diet.
  • Even worse, high doses of one vitamin or mineral may interfere with the absorption or enhance the excretion of another vitamin or mineral. That can create deficiencies.

The same principles apply to what we eat. For example, whole grains and legumes are among the best dietary sources of magnesium. Eliminating those two foods from the diet increases our risk of becoming magnesium deficient. And, that’s just the tip of the iceberg. Any time you eliminate foods or food groups from the diet, you run the risk of creating deficiencies.

For more details about the current study and what it means to you 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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