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The Methylfolate Myths

May 13, 2025 by Dr. Steve Chaney

The Lies Of The Supplement Industry

Author: Dr. Stephen Chaney

How do the myths of the food supplement industry originate? Some of them start innocently enough. They are often based on a kernel of truth which is misinterpreted by some well-meaning medical doctors.

It’s not their fault. We teach future doctors what I call “metabolism light” in medical school. There simply isn’t room in the medical curriculum to teach all the details and nuances of human metabolism.

We also try to teach them the basics of how to interpret scientific literature. However, it takes years of experience to get good at picking out the strengths and weaknesses of clinical studies.

The doctors form their hypothesis and test it on a few patients. If it works, they publish a paper. At that point their idea is picked up by the “sensationalist” bloggers. These are the bloggers who like to focus on the sensational. They delight in writing about “new findings” that go against what the medical profession has been telling you for years.

The bloggers don’t stop there. They usually expand the claims. They ‘cherry pick” the scientific literature by quoting only studies that support their viewpoint and ignoring studies that refute it. In short, they put together a very compelling story. Soon the story is picked up by other bloggers who embellish it further. After it appears in enough sites, people start believing it. A myth is born.

Then supplement companies get in the act. They sense there is money to be made. They manufacture supplements to provide nutrients supported by the myths. They embellish the mythology even more and put together a compelling story to market their products.

This is where the mythology becomes deception. Companies have the responsibility to design their products based on the best science. They have an obligation to tell the truth about their products. When they make claims they know cannot be true, they are lying to you.

The saga of methylfolate is a perfect example of how observations based on a kernel of truth became myths and eventually became downright lies. Let me share that story with you.

The Kernel Of Truth About Methylfolate

Let’s start with one of the “kernel of truth” that launched the whole methyl folate saga. It started with a doctor who was having a very difficult time finding a solution for a patient with some significant health issues. The doctor ordered a genetic test and discovered the patient had a deficiency in the methylene tetrahydrofolate reductase (MTHFR) gene.

The doctor remembered the reaction catalyzed by MTHFR, and a light bulb went off. “Eureka”, he said. His patient must be unable to make N5-methyltetrahydrofolate (commonly referred to as methylfolate or methyl folate), and methylfolate is required for some very important methylation reactions in the cell.

He gave his patient methylfolate, and the patient’s symptoms got better. The doctor leapt to the conclusion that other patients with MTHFR deficiency needed methylfolate as well. Many of those patients responded to methylfolate as well. He didn’t bother to check whether they responded equally well to folic acid. He just assumed methylfolate was the magic elixir.

He wrote a paper on his clinical observations, and the methylfolate story was launched. It all seemed so logical.

However, the story was not nearly as straight forward as the doctor and the people publicizing his findings assumed. Let me walk you through some “Metabolism 101”. Don’t worry. There won’t be a quiz.

Why The Original Assumptions About Methyl Folate Were Misleading

MTHFR mutants only have a partial loss of activity.

Individuals with 2 copies of a mutation from A to C at position 1298 of the MTHFR gene (A1298C homozygotes) comprise about 5% of the US population. They have 60% enzyme activity and appear to be normal in clinical studies.

Individuals with 2 copies of a mutation from C to T at position 677 of the MTHFR gene (C677T homozygotes) have 30% enzyme activity. They comprise about 10% of the US population. C677T homozygotes often have elevated homocysteine levels. The homozygous C677T mutation is associated with depression, anxiety, and mood swings in some people, but not in others (I will come back to the significance of that qualifying statement later).

C677T heterozygotes (one mutant gene) have 65% activity and are normal.

We Don’t Need 100% MTHFR Activity

Our human body is wonderfully designed. For many of our most essential metabolic reactions we have built in redundancy. We don’t require 100% activity of key enzymes. This helps protect us from bad effects of mutations as they arise.

The best analogy I can think of is the US space program. Most space vehicles had built in redundancy so that if one system failed, the mission could go on. For example, you may remember the Hubble space telescope. It was launched with four gyroscopes to keep the telescope pointed in the right direction.

After a few years, one gyroscope gave out. That was not a problem because there were three left. A few years later the second gyroscope gave out. Again, there was no problem because there were still two gyroscopes left.

It was only after the third gyroscope gave out that Hubble became a bit “wonky”, and a space shuttle was sent up to replace the gyroscopes. It is the same with MTHFR. Only when you get down to around 30% activity, does it become a bit wonky”. (That’s about as non-technical as I get.)

Not Everyone With MTHFR Deficiency Experiences Symptoms

This is due to a phenomenon my geneticist friends refer to as penetrance. Simply put, that means that not everyone with the same mutation experiences the same severity of symptoms. That is because the severity of a mutation is influenced by diet, lifestyle, and genetic background.

Let me start with genetic background. In terms of MTHFR mutants you can think of genetic background as being mutations in a related methylation pathway. People who have a mutation in both MTHFR and a gene in a related pathway will experience more severe symptoms and are more likely to require methylfolate. Once you understand penetrance, you realize that individuals requiring methylfolate may represent only a small subset of people with MTHFR mutations.

Penetrance is a concept that most proponents of the methylfolate hypothesis completely ignore. The most severe MTHFR mutation (C677T homozygote) increases the probability that individuals will exhibit symptoms, but some individuals with that mutation are completely normal. Now that you understand the concepts of redundancy and penetrance, you can understand why that is.

When Did The Kernel of Truth Become A Myth?

Up to this point the hype around methyl folate could be chalked up to an honest misunderstanding.

The doctors who published the original papers may not have known that MTHFR mutations only resulted in a partial reduction in enzyme activity.

They probably didn’t know the concepts of redundancy (our cells don’t need 100% enzyme activity) or penetrance (the same mutation may cause severe symptoms in some patients and have no effect in others).

It seemed logical to assume that everyone with a MTHFR mutation might do better with methylfolate supplementation. That was incorrect, but it was an honest mistake.

However, the message was picked up by the bloggers who specialize in sensational stories, especially stories that contradict what experts have been telling you for years. They picked up the methylfolate story and distorted it beyond recognition.

They knew that “natural” is a buzz word, so they told you that methylfolate was natural and folic acid is synthetic.

They told you that methylfolate was better utilized than folic acid.

They told you that methylfolate was more effective than folic acid.

They told you folic acid was toxic. It was going to increase your risk of cancer.

Suddenly, it was no longer about people with MTHFR deficiency. You were told that everyone should avoid folic acid and use methylfolate instead.

On the surface, these pronouncements should not have passed the “If it sounds too good to be true…” test, or in this case, the “If it sounds too bad to be true…” test. You were being asked to believe that folic acid, which has been in use for over 80 years and is backed by hundreds of studies showing it is safe and effective, was neither safe nor effective. You were asked to believe that the government was poisoning you by fortifying foods with folic acid.

However, to make their blogs sound more convincing, they listed clinical studies supporting their stories. The problem is they “cherry picked” the studies that supported their story and ignored the rest. Their bias was particularly outrageous when it came to the “story” that folic acid increases cancer risks. They ignored 10 or 20 studies showing no cancer risk and reported one suggesting it might increase risk. I call that deceptive.

Unfortunately, the myths created by the bloggers have been repeated often enough that many people now believe they are true. It is time for me to debunk the methylfolate myths.

The Methylfolate Myths

Myth: Methylfolate is natural. It comes from whole food. Folic acid is synthetic.

Fact: Methylfolate is chemically synthesized from folic acid. It is physically impossible to extract enough from whole foods. Here are the facts:

Methyfolate is only one of several naturally occurring folates in foods.

The best food sources of folates are beans, leafy greens, and broccoli.

To obtain the RDA of methyfolate for a single tablet you would need to start with 1 cup of lentils, two cups of cooked spinach, or 4 cups of broccoli.

You do the math! It just isn’t possible.

Myth: Methylfolate is better utilized by the body than folic acid.

Fact: This claim is based on levels of methylfolate in the blood after taking supplements providing equivalent amounts of methylfolate and folic acid. However, methylfolate has no biological activity in our blood. The measurement that matters is total folate levels (methylfolate plus other folates) in our cells.

If you take equivalent amounts of folic acid and methylfolate, you end up with identical folate levels in your cells (B.J. Venn et al, The Journal of Nutrition, 132: 3333-3335, 2002). In short, there is no difference in our ability to utilize methylfolate and folic acid.

Myth: If you have a mutation in the MTHFR gene, folic acid isn’t effective.

Fact: MTHFR slightly increases the need for folic acid (from 400 ug to between 600 and 800 ug), but multiple studies show that folic acid supplementation is effective in people with MTHFR mutations.

For example, homocysteine levels are easily measured and are a reliable indicator of methylfolate status.

One study has shown that folic acid and methylfolate were equally effective at lowering plasma homocysteine in people who were MTHFR C677T homozygotes (P. Fohr et al, American Journal of Clinical Nutrition, 75: 275-282, 2002).

That study also showed that folic acid was more effective than methylfolate at lowering homocysteine in people who were C677T heterozygotes and in people with normal MTHFR activity.

Another study showed folic acid was just as effective as a diet providing equivalent quantities of folate from foods at lowering homocysteine levels in people with various MTHFR mutations (A. Ashfield-Watt et al, American Journal of Clinical Nutrition, 76: 180-186, 2002).

At present, lowering of homocysteine levels is the only indicator of methylfolate status for which methylfolate and folic acid have been directly compared. However, there are other studies suggesting that folic acid is likely to be effective for people with MTHFR defects. For example:

Folic acid has been shown in multiple studies to be effective in preventing neural tube defects (M. De-Regil et al, Cochrane Database Systematic Reviews 2010 Oct 6;(10):CD007950. PMID: 20927767), which are highly associated with the C677T MTHFR gene defect.

Three studies have shown that supplementation with folic acid, B12, and B6 slowed cognitive decline in older people with elevated homocysteine levels ( Durga et al, The Lancet, 369: 208-216, 2007); A.D. Smith et al, PLoS ONE 5(9): e12244. doi:10.1371/journal.pone.0012244, 2010); G. Douaud et al, Proceedings of the National Academies of Sciences, 110: 9523-9528, 2013).

In contrast, the one study that substituted methylfolate for folic acid showed no effect (A. McMahon et al, New England Journal of Medicine, 354: 2764-2769, 2006).

Myth: Folic acid causes cancer.

Fact: The few studies suggesting that folic acid supplementation might increase the risk of cancer were “outliers”. By that I mean they contradicted many other studies showing no increased risk.

Scientists are accustomed to this. We know that studies sometimes come up with conflicting results. In some cases, we can point to an error in experimental design or statistical analysis as the cause of the aberrant results.

In other cases, we never know the reason for the differences, so we go with the weight of experimental evidence (what the majority of studies show). The weight of evidence clearly supports the safety of folic acid.

However, that is not enough. If there is the slightest possibility that something causes cancer, we investigate it further. Consequently, the scientific community followed up with larger studies.

Those studies showed either reduced cancer risk or no difference in cancer risk with folic acid supplementation. None of the studies found any evidence that folic acid increased cancer risk. I have covered this in detail for folic acid and colon cancer risk in a previous issue of “Health Tips From The Professor”.

There have also been a couple of small studies suggesting that folic acid might increase the risk of prostate and breast cancer. Although these were small, individual studies, they have been widely hyped by the methylfolate advocates. Once again, the definitive study has been done (S.E. Vollset et al, The Lancet, 381: 1029-1036, 2013).

It was a meta-analysis of 13 placebo-controlled studies involving over 50,000 subjects. The results were clear cut. Folic acid supplementation caused no increase in overall cancer risk, and no increase in the risk of colon cancer, prostate cancer, breast cancer, or any other individual cancer. Moreover, the average dose of folic acid in those studies was 2 mg/day, which is 5 times the RDA.

Of course, the bloggers and the companies selling methylfolate supplements ignore the definitive studies showing folic acid does not increase cancer risk. The myths and lies continue.

Myth: Folic acid can mask a B12 deficiency.

Fact: True but irrelevant if you use a supplement with folic acid and B12 in balance.

The Lies Of The Supplement Industry

If you are writing a blog, you are covered by “freedom of speech”. You can say whatever you want. It doesn’t have to be true. However, if you are a supplement manufacturer, you are held to a higher standard. Ignorance is no longer an excuse. You can no longer cherry pick the “facts” you like and ignore the rest. You are ethically obligated to research all the available literature and be guided by the best scientific evidence.

Reputable companies have been guided by scientific evidence and have not jumped on the methylfolate bandwagon. They know folic acid is both safe and effective in a wide variety of clinical situations. They also know that, while methylfolate may be just as effective as folic acid, it has not been shown to be superior to folic acid for any clinical application.

They may offer a methylfolate option for people who believe they need it. But they make no claim that it is superior to their products containing folic acid.

Less reputable companies, however, sensed money to be made by capitalizing on the buzz around methyl folate. They repeated the myths of the bloggers and claimed their products were superior to others on the market. They call it marketing. I call it lying. They have an obligation to fact check their claims and only make claims that are true.

Let me give you an example. In preparing for this article, I looked at the claims of several companies that were promoting their methylfolate supplements. One in particular claimed they had studies showing:

1) Their methylfolate supplement was effective at reducing the risk of adverse pregnancy outcomes.

2) Their methylfolate supplement was twice as bioavailable as folic acid.

3) Their methylfolate supplement was able to lower homocysteine levels better than conventional folic acid supplementation.

All three studies were bogus.

With respect to the first study, it was likely true that their methylfolate supplement decreased adverse pregnancy outcomes. But there are dozens of studies showing that folic acid does the same thing.

And because they did not compare methylfolate and folic acid supplementation in their studies, they have no basis for claiming their supplement was superior.

The second study compared levels of methylfolate and folic acid in the blood. As I mentioned above, methylfolate has no biological activity in our blood. The measurement that matters is total folate levels (methylfolate plus other folates) in our cells. And previous studies have shown that equivalent amounts of methylfolate and folic acid give identical amounts of methyfolate in our cells.

The third study compared their supplement, which contained B6, B12, zinc, and betaine in addition to methylfolate, to folic acid alone. That’s comparing apples to oranges. That is because there are three pathways for lowering homocysteine levels, and B6, B12, and betaine play important roles in each of these pathways.

- B12 is an integral part of the enzyme methionine synthase, an enzyme that converts homocysteine to the amino acid methionine. Methylfolate transfers its methyl group to the enzyme-bound vitamin B12, and methyl B12 transfers the methyl group to homocysteine, which converts it to methionine. In other words, methylfolate cannot lower homocysteine levels by itself. It needs vitamin B12.

- Betaine also serves as a methyl donor in another pathway for converting homocysteine to methionine by an enzyme called betaine-homocysteine methyltransferase.

- B6 is essential for yet another pathway that lowers homocysteine levels by converting homocysteine to the amino acid cysteine.

You might argue that the company was simply ignorant of the importance of B6, B12, and betaine for lowering homocysteine levels. However, that is unlikely. Why else would they have included B6, B12, and betaine in their supplement?

They must have known the study they designed was bogus. That suggests they conducted the study with the sole purpose of deceiving you, the consumer. I call that lying.

Finally, in case you were wondering, I am not recommending you select a single supplement with folic acid, B6, and B12. I do recommend you get your folic acid from a multivitamin or B complex supplement that provides all three B vitamins in balance.

Betaine deficiency is very rare, so I don’t include betaine in my recommendations.

What Does This Mean For You?

MTHFR mutations only result in partial loss of activity. Most individuals with MTHFR defects remain symptom free with the RDA, or slightly above the RDA, of folic acid.

However, there may be some individuals with a MTHFR defect and additional gene defects in metabolic pathways involving methylation who might benefit from methylfolate. This is due to a phenomenon that geneticists call penetrance and would likely represent a small subset of the population with MTHFR defects.

Finally,the claims that everyone would benefit from methylfolate instead of folic acid are false. They are contradicted by human metabolism and multiple published clinical studies.

In short, folic acid has been used for over 80 years. There are hundreds of clinical studies showing it is safe and effective, even in most individuals with a MTHFR deficiency. I can’t tell you whether the companies selling methylfolate are ignorant of basic metabolism and the published studies refuting their claims or whether they are purposely trying to deceive the public—but neither is a good thing.

The Bottom Line

Some supplement manufacturers are claiming that methylfolate is more natural and more effective than the folic acid that has been used in supplements for the past 80 years. In this issue of “Health Tips From the Professor” I debunk the methylfolate myths used by the supplement manufacturers to sell their methylfolate products.

I can’t tell you whether the companies selling methylfolate are ignorant of basic metabolism and the published studies refuting their claims or whether they are purposely trying to deceive the public—but neither is a good thing.

For more specifics, 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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My posts and “Health Tips From the Professor” articles carefully avoid claims about any brand of supplement or manufacturer of supplements. However, I am often asked by representatives of supplement companies if they can share them with their customers.

My answer is, “Yes, as long as you share only the article without any additions or alterations. In particular, you should avoid adding any mention of your company or your company’s products. If you were to do that, you could be making what the FTC and FDA consider a “misleading health claim” that could result in legal action against you and the company you represent.

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

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About The Author

Dr. Chaney has a BS in Chemistry from Duke University and a PhD in Biochemistry from UCLA. He is Professor Emeritus from the University of North Carolina where he taught biochemistry and nutrition to medical and dental students for 40 years. Dr. Chaney won numerous teaching awards at UNC, including the Academy of Educators “Excellence in Teaching Lifetime Achievement Award”. Dr Chaney also ran an active cancer research program at UNC and published over 100 scientific articles and reviews in peer-reviewed scientific journals. In addition, he authored two chapters on nutrition in one of the leading biochemistry textbooks for medical students.

Since retiring from the University of North Carolina, he has been writing a weekly health blog called “Health Tips From the Professor”. He has also written two best-selling books, “Slaying the Food Myths” and “Slaying the Supplement Myths”. And most recently he has created an online lifestyle change course, “Create Your Personal Health Zone”. For more information visit https://chaneyhealth.com.

For the past 53 years Dr. Chaney and his wife Suzanne have been helping people improve their health holistically through a combination of good diet, exercise, weight control and appropriate supplementation.

Is Folate Needed For Strong Bones?

October 8, 2024 by Dr. Steve Chaney

Why Is Folate Needed For Strong Bones?

Author: Dr. Stephen Chaney

When most people think of the nutrients required to build strong bones, they just think of calcium and vitamin D. This is understandable because these two nutrients are essential for building healthy bone.

But in reality “it takes a village” to build strong bones.

The bone matrix also contains magnesium, zinc, copper, and manganese. They are also needed.

- Fun fact: As an undergraduate at the University of Southern California my wife, Suzanne, worked for Dr. Paul Saltman, the biochemist who discovered the importance of these nutrients for building healthy bone.

Vitamin C is required to build collagen, the foundation on which bone is built, and the cartilage that helps bones resist fractures.

Vitamin K delivers calcium to osteoblasts, the cells responsible for building bone.

But a new study (L Zhou et al, BMC Musculoskeletal Disorders, 25: 487, pages 1-9, 2024) suggests that folate is also important for building strong bones and preventing osteoporosis as we age. I didn’t see that one coming. So, let me start by explaining why folate may be important for bone health before I review the study.

Why Is Folate Needed For Strong Bones?

There are four facts we need to know about human metabolism to understand the effect of folate on bone health.

Fact 1: We tend to think of bone as a permanent, unchanging part of our body. But that’s not true. As we move about our bones experience wear and tear. As they age they become more brittle and susceptible to fracturing.

So, our bodies have a process for continuously removing old bone and replacing it with new bone. Although you don’t notice the change, your bones today are not the same bones you had 10 or 15 years ago. They are continually being renewed.

The cells responsible for removing the old bone are called osteoclasts, and the cells responsible for building new bone are called osteoblasts. It is the perfect balance between osteoclast and osteoblast activity that keeps our bones strong.

Fact 2: When cellular folate levels are low, an amino acid metabolite called homocysteine accumulates in our cells and in our blood.

Fact 3: (This is the one I didn’t know until I looked it up): Homocysteine increases osteoclast activity and decreases osteoblast activity.

This tips the balance towards breaking down our bones. For young people that makes it more difficult to build strong, healthy bones. For older people that increases the risk of osteoporosis.

Fact 4: To clear up any confusion before we get started, I should tell you that the term “dietary folates” often includes folates from foods and folic acid from supplements. That is because folic acid is efficiently taken up by our cells and converted to folates in the cell.

And when methyl folate and folic acid are compared head to head in clinical studies, methyl folate offers no advantage over folic acid, even in individuals with mutations in the MTHFR gene. For more detail on this statement, go to https://www.chaneyhealth.com/healthtips/ and type “methy folate” in the search box.

How Was The Study Done?

The investigators used data from the CDC’s 2017-2020 NHANES (National Health And Nutrition Examination Survey) database. The NHANES program has been obtaining health and nutrition data from approximately 5,000 US citizens a year since 1969. Every 4 years the data are compiled into a database that can be used for studies like this one.

The investigators excluded participants who were missing important information such as calcium, vitamin D, or folate intake and bone density measurements. This left 2297 participants for the current study.

The participants were 49.9% female, 73% white, and the average age was 64 years. The prevalence of osteoporosis in this group was 6.92%, which is similar to other estimates of osteoporosis prevalence in this age group.

Dietary intake was based on two 24-hour dietary recalls. Bone density in the femur region was assessed by DXA radiological imaging. Osteoporosis was defined as a bone mineral density of <0.64 g/cm² for women and <0.68 g/cm² for men.

The study measured the correlation between dietary folate intake and prevalence of osteoporosis.

Is Folate Needed For Strong Bones?

The investigators separated the participants into 3 groups based on dietary folate intake: lowest (<264 mcg/day), middle (264-390 mcg/day), and highest (>390 mcg/day). For reference the daily value (DV) for folate is 400 mcg/day for adults in this age group.

When adjusted for other factors that affect bone density such as calcium, vitamin D, smoking, and alcohol consumption, those with the highest dietary intake of folates compared to those with the lowest dietary intake of folates:

Decreased their risk of osteoporosis by 70%.

And when the data were broken down by gender and age, the highest intake of dietary folates:

Decreased the risk of osteoporosis by 82% for women.

- Also, decreased the risk of osteoporosis for men. But the decrease was not statistically significant (Because men are less likely to develop osteoporosis than women, a much larger study would likely be required to show a statistically significant decreased risk for men.)

Decreased the risk of osteoporosis by 70% for people over 60.

- Did not significantly decrease the risk of osteoporosis for people under 60 (Osteoporosis is rare in people under 60.)

In short, adequate intake of folates (including folic acid) significantly decreases the risk of osteoporosis for those who are at highest risk, namely postmenopausal women over 60.

When the investigators did a dose response plot they found an L-shaped relationship between dietary folate and the risk of osteoporosis. They concluded that:

Dietary folate intake between 264 and 569 mcg/day was effective in preventing osteoporosis in post-menopausal women. Intakes above 569 mcg/day provided little or no additional benefit.

The authors concluded, “This finding suggests the potential importance of dietary folate for preventing and managing osteoporosis.”

“However, further longitudinal research and randomized controlled trials are necessary to elucidate the causal association between dietary folate intake and the risk of osteoporosis.”

What Does This Study Mean For You?

I am not suggesting that you should throw out your calcium and vitamin D supplement and rely on a folic acid supplement to build strong bones and prevent osteoporosis.

Calcium and vitamin D are absolutely essential for building strong bones. But they are not sufficient by themselves. It takes a holistic approach to build strong bones.

I have previously alerted you to the importance of vitamin C, vitamin K, magnesium, zinc, copper, and manganese for building strong bones. This study suggests I may need to add folic acid to the list. And who knows how many additional nutrients may play a role we don’t yet know about.

And it’s not just nutrients. There are many other lifestyle factors that influence the health of our bones. I have described what it takes to have a “bone healthy lifestyle” in a previous issue of “Health Tips From the Professor”.

This is why so many studies looking at the effect of calcium/vitamin D supplements on the risk of developing osteoporosis have come up empty. These studies were asking if calcium and vitamin D were “magic bullets” that could prevent osteoporosis on their own.

The answer to that question appears to be, “No”. But it isn’t the right question. As I have said before, “When clinical studies ask the wrong question, they get the wrong answer.”

Calcium and vitamin D are essential for bone formation, but they aren’t sufficient by themselves. It takes a village. Any study that ignores that is doomed to failure.

What does that mean for you? My recommendation is simple. If you want to build strong bones and reduce your risk of osteoporosis:

Start with a comprehensive multivitamin/multimineral supplement to make sure your bases are covered.

If your intake of calcium and vitamin D are below DV values (1,300 mg of calcium and 600-800 IU of vitamin D for adults in this age range), consider a calcium/vitamin D supplement.

Follow a “bone healthy lifestyle”.

The Bottom Line

A recent study suggests that dietary folate is important for building strong bones and preventing osteoporosis in post-menopausal women.

In this article I review the study, put it into perspective, and discuss what it means for you.

For more details about this study and what it means for 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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For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

____________________________________________________________________________

About The Author

For the past 45 years Dr. Chaney and his wife Suzanne have been helping people improve their health holistically through a combination of good diet, exercise, weight control and appropriate supplementation.

Which Nutrients Prevent Prenatal Depression?

May 14, 2024 by Dr. Steve Chaney

What Does This Study Mean For You?

Author: Dr. Stephen Chaney

Yes, you read the headline correctly. Everyone talks about postnatal depression. But prenatal depression is also a “thing”, especially during the third trimester.

Worldwide, 4-20% of women experience some degree of depression during the third trimester – with pregnant women in high-income countries at the lower end (4-10%) of depression risk.
In contrast, the incidence of postnatal depression is 10-15%.

It is probably no coincidence that the incidence of depression is greatest during the third trimester and during the postnatal period.

The third trimester is the most difficult part of pregnancy for many women.
When a woman brings her baby home from the hospital her orderly life becomes chaotic.

But what role does nutrition play?

While not definitive, many studies suggest that supplementation with B vitamins, especially folic acid, B6, and B12; omega-3 fatty acids; vitamin D; and iron reduce the risk of postnatal depression.
However, there is much less information on which nutrients reduce the risk of prenatal depression.

Based on studies suggesting both iron and vitamin D deficiencies may negatively impact mental health, the authors of this study (JL Evanchuk et al, The Journal Of Nutrition. 154, 174-184, 2024) set out to determine whether iron and/or vitamin D deficiencies increase the risk of prenatal depression during the first trimester.

How Was This Study Done?

The authors recruited 2189 newly pregnant mothers from Calgary and Edmonton in Ontario Canada between 2009 and 2012. Participants in the study visited clinics in the area upon entry into the study; midway through the first, second, and third trimesters; and at multiple timepoints up to 3 months during the postpartum period.

In addition to the usual pregnancy wellness tests, participants filled out a 24-hour dietary recall and a Supplemental Intake Questionnaire to determine intakes of iron and vitamin D.

Note: The participants were all advised to take some form of prenatal supplement during the study. That’s because prenatal supplements are considered “the standard of care” for pregnant woman, so it would be considered unethical not to include a prenatal supplement in this study.

At the mid-point of the second trimester blood samples were drawn and analyzed for biomarkers of iron and vitamin D insufficiency. For iron the biomarkers were serum ferritin, soluble transferrin receptor, and hepcidin. For vitamin D, the biomarkers were 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 3-epi-25-hydroxyvitamin D.

Iron deficiency was defined as serum ferritin levels <15 µg/L. Vitamin D insufficiency was defined as 25-hydroxyvitamin D levels < 75nmol/L. The other biomarkers were used to confirm these diagnoses.

Maternal depression was measured midway through the third trimester and ~3 months postpartum using 10-item questionnaire called the Edinburg Postnatal Depression Scale (EPDS). The EPDS ranks depression on a scale of 0 to 30, with a score of ≥13 considered an indication of likely depression.

The characteristics of the women enrolled in this study were:

Average age = 31.5
Average prepregnancy BMI = 23 (healthy weight).
Married or cohabitating with a partner = 97%.
Highly educated (college or postgraduate degree) = 68%.
Income above $70,000/year = 78%.
First child = 54%.
White = 80%.

Based on the Edinburg Depression Scale, probably depression for the 1822 women who completed the study was 5.6% during the third trimester and 4.4% 3 months postpartum.

Note: The low incidence of depression seen in this study was probably due to:

The women in this study were of high socioeconomic status and were receiving excellent healthcare.

The women in this study were taking prenatal supplements that provided both iron and vitamin D.

Which Nutrients Prevent Prenatal Depression?

As I mentioned when describing how the study was designed, all participants in this study were advised to take a prenatal supplement. Consequently:

94% of the women in this study were taking a supplement containing iron with an average supplemental iron intake of 26 mg/day.

- Note: The RDA for iron during pregnancy is 30 mg/day and most prenatal supplements provide 27 mg/day.

68% of the women in this study were taking a supplement containing vitamin D, with an average supplemental vitamin D intake of 330 IU/day.

- Note: The RDA for vitamin D during pregnancy is 600 IU/day, but most prenatal supplements provide far less than that.

When the investigators looked at iron and vitamin D status during the second trimester:

63.3% of the women had adequate levels of both iron and vitamin D.

14.8% of the women were low in vitamin D but had adequate iron levels.

18.4% of the women were low in iron but had adequate levels of vitamin D.

3.5% of the women were low in both iron and vitamin D.

RDAs are supposed to be enough to meet the nutrient requirements of 97-98% of healthy individuals, so it is perhaps surprising to see so many women with insufficient levels of iron (21.9%) and/or vitamin D (18.3%) in this study. This could be due to:

Insufficient intake.

- This is a likely explanation for vitamin D because the supplements women were using in this study provided around half the recommended RDA for vitamin D and the women lived at a northern latitude where sun exposure makes a small contribution to vitamin D levels.

- However, this is a less likely explanation for insufficient iron levels because the supplements provided 87% of the RDA for iron.

Inadequate RDAs. Studies like this one provide a rigorous test for the adequacy of existing RDAs. This study suggests the existing RDA for iron is adequate to meet the needs of ~80% of pregnant women, which is reassuring. However, it may need to be increased to reach the goal of meeting the iron requirements for 97-98% of pregnant women.

But the important question is whether the iron and vitamin D insufficiencies seen in this study mattered. The data suggested that they did.

For pregnant women with low iron, but adequate vitamin D levels in the second trimester, there was a small, but significant, increased risk of experiencing depression symptoms in the third trimester.

For pregnant women with low iron and vitamin D levels in the second trimester, the risk of experiencing depression symptoms in the third trimester increased by 2.2 points in the 30-point Edinburg Depression Scale.

- This is equivalent to a 7.4% increased risk of depression from deficiencies of iron and vitamin D alone – and these are only 2 of at least 8 nutrients thought to be associated with maternal depression.

The authors concluded, “Maternal iron and vitamin D biomarkers, measured during midpregnancy, were independently associated with third trimester maternal depression symptoms…This investigation is one of the first to report on the combined adequacy of maternal iron and vitamin D status during pregnancy and its impact on maternal depression.

The novelty of this work reinforces the need to ask similar questions [with other nutrients and] in other pregnant populations. Future investigations should report on the status of multiple nutrients and explore their independent and combined impact on health outcomes of pregnant individuals and their children.”

What Does This Study Mean For You?

Depression during pregnancy is bad for you. And because your fetus can sense your mood, it is bad for your baby. So, what should you do?

You can consult with your doctor about which antidepressants are safe to take during pregnancy. But the truth is there are no good choices. There are some antidepressants that are off limits. There are other antidepressants that appear to have little short-term risks, but we have no idea if there are long-term risks for your child.

So, what about natural approaches? Let’s start with nutrition.

The biggest takeaway from this study is that prenatal supplements may not be sufficient to prevent nutritional deficiencies that may cause prenatal depression for pregnant women.

This does not mean that every pregnant woman suffering prenatal depression should increase their iron and vitamin D levels.

However, if you are experiencing prenatal depression, you might want to ask your doctor about checking your iron and vitamin D status to determine if extra iron and/or vitamin D would be beneficial.

And to put this study into its proper perspective we need to remember that iron and vitamin D deficiencies are only two of many nutrients that may increase the risk of prenatal depression.

For example, in addition to iron and vitamin D, prenatal depression is associated with deficiencies of:

B vitamins, especially folate, B6 and B12. Most prenatal supplements provide the recommended RDA of folate for pregnant women, but not all contain RDA amounts of B6 and B12.

Calcium and magnesium. Very few prenatal supplements provide the recommended RDA for calcium and magnesium.

Omega-3s, especially DHA. Very few prenatal supplements provide DHA, and the few that do usually provide inadequate amounts of DHA.

So, when you are having your nutrition conversation with your doctor, you might not want to limit your conversation to iron and vitamin D.

Alternately, as I suggested last week’s issue of “Health Tips From the Professor”, you might wish to add a multivitamin supplement and an omega-3 supplement providing at least 300 mg of DHA plus EPA. This simple step would be sufficient to assure you have adequate levels of nutrients thought to be important for reducing the risk of prenatal depression.

And, of course, there are other lifestyle factors, as well. For example:

Diets high in highly processed foods are known to increase the risk of depression. And whole food, primarily plant-based diets decrease the risk of depression.

Overweight and obesity increase the risk of depression.

Regular exercise decreases the risk of depression.

The Bottom Line

A recent study looked at whether taking a prenatal supplement was sufficient to eliminate deficiencies of iron and vitamin D during pregnancy and whether deficiencies of these two nutrients during the second trimester of pregnancy increased the risk of depression during the third trimester.

When the investigators looked at iron and vitamin D status during the second trimester:

14.8% of the women were low in vitamin D but had adequate iron levels.

18.4% of the women were low in iron but had adequate levels of vitamin D.

3.5% of the women were low in both iron and vitamin D.

But the important question is whether the iron and vitamin D insufficiencies seen in this study mattered. The data suggested that they did.

For pregnant women with low iron, but adequate vitamin D levels in the second trimester, there was a small, but significant, increased risk of experiencing depression symptoms in the third trimester.

For pregnant women with low iron and vitamin D levels in the second trimester, the risk of experiencing depression symptoms in the third trimester increased by 2.2 points in the 30-point Edinburg Depression Scale.

This is equivalent to a 7.4% increased risk of depression from deficiencies of iron and vitamin D alone.

When you consider that iron and vitamin D are just two of 8 or more nutrients thought to be important for preventing depression during pregnancy, the question becomes what you can do to decrease your risk of developing depression during pregnancy and after the birth of your child.

For more details about the study and what it means for 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.

____________________________________________________________________________

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

___________________________________________________________________________

About The Author

Prenatal Supplements Strike Out Again

May 9, 2023 by Dr. Steve Chaney

Is It Three Strikes And You Are Out?

Author: Dr. Stephen Chaney

If you are pregnant, you want the best for your unborn baby. Your doctor has recommended a prenatal supplement, but do the prenatal supplements on the market meet your needs? A few months ago, I shared two studies that concluded that most prenatal supplements on the market are woefully inadequate.

In fact, the authors said, “[Our] analysis found that prenatal supplements vary widely in content, often only contain a subset of essential vitamins, and the levels were often below…recommendations.”

In other words, their study found that most prenatal vitamins on the market may not be adequate to support your needs and the needs of your child through pregnancy and breastfeeding.

Now, a third study on the topic has been published (KA Saunders et al, American Journal of Clinical Nutrition, 117: 823-829, 2023. It differs from the previous studies in that:

1) The previous two studies took a comprehensive approach, while this study focused on 6 key nutrients.

The previous studies included all nutrients important for a healthy pregnancy including choline, iodine, and vitamin K, which have only recently been shown to be important for a healthy pregnancy.

This study focused on 6 nutrients, vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids, which have long been recognized as essential for a healthy pregnancy.

2) The previous two studies focused on prenatal supplements, while this study focused on all supplements that might be taken by pregnant women.

3) The previous two studies asked whether supplements provided recommended amounts of all nutrients needed for a healthy pregnancy. This study took a “Goldilocks approach” and asked whether levels of these 6 essential nutrients were appropriate (“just right”). The study:

Started by determining the intake of these 6 key nutrients by American women. The authors of the study then added the amount of each nutrient provided by the supplements in their study to the amount of that nutrient in the diet of American women and:

- Calculated the minimum amount of each nutrient that would be needed to assure that 90% of American women taking a particular supplement would meet the recommended intake for pregnant and lactating women.

- Calculated the maximum amount of each nutrient provided by supplements in their study to assure that that 90% of American women taking that supplement would not get potentially toxic amounts of that nutrient.

In other words, for each of the 6 nutrients they calculated a supplemental dose range that was neither too low nor too high. They called this the “appropriate dose range” for each nutrient. Goldilocks would have called it “just right”.

I’m sure you are anxiously waiting to learn what their study found. But before we go there, I will describe how the study was done.

How Was The Study Done?

For the dietary intake portion of the study, the authors used dietary intake data previously collected from the Environmental Influences on Child Health Outcomes (ECHO) study.

The ECHO study is a consortium of 69 medical centers across multiple states. It is an observational study of mothers and their offspring designed to understand the effects of early life exposures on child health and development.

The current study analyzed dietary intake data for 2450 participants from 6 medical centers across 5 states in the ECHO study. The women in this study were diverse with respect to ethnicity, education, and weight.

All pregnant women in the current study completed at least one 24-hour dietary recall between 6-week gestation until delivery (24% completed one dietary recall. 76% completed two or more dietary recalls). Dietary intake was generally assessed with an expert interviewer and included all foods and beverages consumed in the previous 24 hours.

For the supplement portion of the study, the authors used the NIH Dietary Supplement Label Database because it is the most complete listing of supplements in the US. The authors selected 20,547 supplements that contained at least one of the 6 essential nutrients from this database.

To determine which of the 20,547 supplements contained appropriate levels of the 6 nutrients (vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids) selected for this study, the authors used the process described in the introduction above. Briefly:

The authors added the amount of each nutrient provided by the supplements in their study to the amount of that nutrient in the diet of American women and:

Calculated the minimum amount of each nutrient that would be needed to assure that 90% of American women taking a particular supplement would meet the recommended intake for pregnant and lactating women.

Calculated the maximum amount of each nutrient provided by supplements in their study to assure that that 90% of American women taking that supplement would not get potentially toxic amounts of that nutrient.

In other words, for each of the 6 nutrients they calculated a supplemental dose range that was neither too low nor too high. They called this the “appropriate dose range” for each nutrient.

Why Are The 6 Nutrients Included In This Study Important?

Dietary Intake Is Often Inadequate

The diet analysis of pregnant American women in this study found:

42% were at risk of inadequate vitamin A intake.

96% were at risk of inadequate vitamin D intake.

45% were at risk of inadequate folic acid intake.

55% were at risk of inadequate calcium intake.

93% were at risk of inadequate iron intake.

67% were at risk of inadequate omega-3 intake.

The percentage of women at risk for inadequate intake of these nutrients varied with age, ethnicity, and income levels. But the overall message is clear. Most American women are not getting enough of these essential nutrients from their diet alone.

The Risk of Inadequate and Excessive Intake Of These Nutrients

These 6 nutrients were chosen in part because reviews by the Cochrane Collaboration have concluded that inadequate intake of these nutrients are associated with complications during pregnancy and delivery. They can also adversely affect the health and normal development of the baby.

This is important because the Cochrane Collaboration is considered the Gold Standard of clinical studies. You can find a more detailed description of Cochrane Collaboration studies and why they are the Gold standard here.

[Note: The Cochrane Collaboration has not yet evaluated choline, iodine, and vitamin K for pregnant women, but their inclusion in prenatal supplements is supported by multiple clinical studies.]

In addition, excess intake of all these nutrients except omega-3s can harm both the fetus and the mother. The is why the Food and Nutrition Board has set ULs (Upper Limits – the level above which toxicity can occur) for 5 of the 6 nutrients. This is important because previous studies have suggested that up to 25% of women may be getting toxic levels of one or more of these nutrients when you consider both their dietary intake and their prenatal supplement.

Summary

In other words, both too little and too much of these nutrients can harm the mom and her baby. It is critical that prenatal supplements get the dosing right.

It is for that reason that the authors of this study have set an “appropriate dose range” (high enough that 90% of women have enough of each nutrient to prevent deficiency and low enough that 90% of women do not exceed the UL for each nutrient) as the standard for evaluating the adequacy and safety of supplements for pregnant women.

Prenatal Supplements Strike Out Again

Of the 20,547 supplements (421 labeled as prenatal supplements) available on the US market as of December 31, 2022, the investigators reported that:

Only 69 (0.3%) supplements contained all 6 nutrients considered essential for a healthy pregnancy.

Only 1 supplement contained all 6 nutrients at the appropriate doses, and it wasn’t even labeled as a prenatal supplement.

In addition:

One supplement containing all 6 nutrients put 100% of the women in their study at risk for excessive intake of folic acid.

Another supplement containing all 6 nutrients put 46% of the women in their study at risk of inadequate calcium intake.

The authors concluded, “Almost no US dietary supplements provide key nutrients in the doses needed for pregnant women. Affordable and convenient products that fill the gap between food-based intake and estimated requirements of pregnancy without inducing excess intake are needed to support pregnant women and their offspring.”

In short, the conclusion of this study can be summed up as, “Prenatal Supplements Strike Out Again”.

[Note: It sometime takes a while for supplement labels to be posted in the NIH Dietary Supplement Label Database. The authors acknowledged that this study may not include supplements introduced or reformulated in the last quarter of 2022.]

Is It Three Strikes And You Are Out?

If you are pregnant or thinking of becoming pregnant, this should be a wake-up call.

70% of pregnant women in this country take prenatal supplements, usually based on recommendations by their health care provider. They assume the prenatal supplements meet their needs and the needs of their unborn baby.

Yet three studies evaluating the adequacy of prenatal supplements have been published in the past few months. They took very different approaches in evaluating the supplements. But all three studies concluded that the vast majority of prenatal supplements on the market are woefully inadequate.

You may be wondering, “Is it three strikes, and you are out?” Are there no decent prenatal supplements on the market? The answer to those questions is, “No. There are good prenatal supplements on the market.”

You may be wondering how I can say that in the face of such overwhelming negative data. That’s because while all 3 studies were very good studies, they each had “blind spots”:

1) Each of the studies used very stringent criteria for identifying adequate prenatal supplements. In some cases, their criteria were stricter than the RDA recommendations and the recommendations of the American College of Obstetrics and Gynecology for pregnant and lactating women. It could be argued that their criteria were too stringent.

2) In the case of the current study, it could also be argued that evaluating only 6 nutrients is not a good criterion for evaluating the adequacy of prenatal supplements. For example, I looked up the one supplement rated as adequate in this study. It does provide appropriate doses of the 6 nutrients this study focused on. It also provides appropriate doses of vitamin K and iodine. But it does not provide choline. It is a very good supplement for women, but it is not the perfect prenatal supplement.

So, what can you do? How can you find the best prenatal supplement for you? Unfortunately, you cannot rely on advice from your friends or your health professional. You cannot rely on advertisements. That is a good place to start, but you have to do your own sleuthing.

With that in mind, I have listed 7 simple rules for selecting the best possible prenatal supplement in my article about the first two studies. Use these rules for evaluating every prenatal supplement you come across. Happy sleuthing.

The Bottom Line

A recent study evaluated all 20,547 supplements on the US market to see if they met the needs of pregnant women in this country.

They focused on 6 nutrients (vitamin A, vitamin D, folic acid, calcium, iron, and omega-3s) known to be essential for a healthy pregnancy.

They determined the dietary intake for all 6 nutrients in a cross section of pregnant women in the US.

They added the amount of the 6 nutrients in each of the 20,547 supplements to the dietary intake of those nutrients by pregnant women.

They then asked which supplements provided the “appropriate dose” of all 6 nutrients. They defined “appropriate dose” as the dose range that was.

- High enough to prevent deficiency of that nutrient in 90% of pregnant women taking the supplement…and…

- Low enough to prevent toxicity from that nutrient in 90% of pregnant women taking the supplement.

In other words, for each of the 6 nutrients they calculated a supplemental dose range that was neither too low nor too high.

Of the 20,547 supplements (421 labeled as prenatal supplements) available on the US market:

Only 69 (0.3%) supplements contained all 6 nutrients they considered essential for a healthy pregnancy.

Only 1 supplement contained all 6 nutrients at the appropriate doses, and it wasn’t even labeled as a prenatal supplement.

If you are pregnant or thinking of becoming pregnant, this should be a wake-up call.

Yet three studies evaluating the adequacy of prenatal supplements have been published in the past few months. And all three studies concluded that the vast majority of prenatal supplements on the market are woefully inadequate.

You may be wondering how I can say that in the face of such overwhelming negative data. That’s because while all 3 studies were very good studies, they each had “blind spots”:

For more details on this study and 7 tips on finding the best prenatal supplement for 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.

____________________________________________________________________________

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

Which Supplements Are Good For Your Heart?

February 7, 2023 by Dr. Steve Chaney

How Should You Interpret This Study?

Author: Dr. Stephen Chaney

February is Heart Health month. So, it is fitting that we ask, “What is the status of heart health in this country?” The American Heart Association just published an update of heart health statistics through 2019 (CW Tsao et al, Circulation, 145: e153-e639, 2022). And the statistics aren’t encouraging. [Note: The American Heart Association only reported statistics through 2019 because the COVID-19 pandemic significantly skewed the statistics in 2020 and 2021].

The Good News is that between 2009 and 2019:

All heart disease deaths have decreased by 25%.
Heart attack deaths have decreased by 6.6%.
Stroke deaths have decreased by 6%.

The Bad News is that:

Heart disease is still the leading cause of death in this country.
Someone dies from a heart attack every 40 seconds.
Someone dies from a stroke every 3 minutes.

Diet, exercise, and weight control play a major role in reducing the risk of heart disease. Best of all, they have no side effects. They represent a risk-free approach that each of us can control.

But is there something else? Could supplements play a role? Are supplements hype or hope for a healthy heart?

All the Dr. Strangeloves in the nutrition space have their favorite heart health supplements. They claim their supplements will single-handedly abolish heart disease (and help you leap tall buildings in a single bound).

On the other hand, many doctors will tell you these supplements are a waste of money. They don’t work. They just drain your wallet.

It’s so confusing. Who should you believe? Fortunately, a recent study (P An et al, Journal of the American College of Cardiology, 80: 2269-2285, 2022) has separated the hype from the hope and tells us which “heart-healthy” supplements work, and which don’t.

How Was This Study Done?

This was a major clinical study carried out by researchers from the China Agricultural University and Brown University in the US. It was a meta-analysis, which means it combined the data from many published clinical trials.

The investigators searched three major databases of clinical trials to identify:

884 randomized, placebo-controlled clinical studies…

Of 27 types of micronutrients…

With a total of 883,627 patients…

Looking at the effectiveness of micronutrient supplementation lasting an average of 3 years on either…

- Cardiovascular risk factors like blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides…or…

- Cardiovascular outcomes such as coronary heart disease (CHD), heart attacks, strokes, and deaths due to cardiovascular disease (CVD) and all causes.

[Note: Coronary heart disease (CHD) refers to build up of plaque in the coronary arteries (the arteries leading to the heart). It is often referred to as heart disease and can lead to heart attacks (myocardial infarction). Cardiovascular disease (CVD) is a more inclusive term that includes coronary heart disease, stroke, congenital heart defects, and peripheral artery disease.]

The investigators also included an analysis of the quality of the data in each of the clinical studies and rated the evidence of each of their findings as high quality, moderate quality, or low quality.

Which Supplements Are Good For Your Heart?

The top 3 heart-healthy supplements in this study were:

Omega-3 Fatty Acids:

Increased HDL cholesterol and decreased triglycerides, both favorable risk factors for heart health.
Deceased risk of heart attacks by 15%, all CHD events by 14%, and CVD deaths by 7% (see definitions of CHD and CVD above).
The median dose of omega-3 fatty acids in these studies was 1.8 g/day.
The evidence was moderate quality for all these findings.

Folic Acid:

Decreased LDL cholesterol (moderate quality evidence) and decreased blood pressure and total cholesterol (low quality evidence).
Decreased stroke risk by 16% (moderate quality evidence).

Coenzyme Q10:

Decreased triglycerides (high quality evidence) and reduced blood pressure (low quality evidence).
Decreased the risk of all-cause mortality by 32% (moderate quality evidence).
These studies were performed with patients diagnosed with heart failure. Coenzyme Q10 is often recommended for these patients, so the studies were likely performed to test the efficacy of this treatment.

There were three micronutrients (vitamin C, vitamin E, and vitamin D) that did not appear to affect heart disease outcomes.

Finally, as reported in previous studies, β-carotene increased the risk of stroke, CVD mortality, and all-cause mortality.

In terms of the question I asked at the beginning of this article, this study concluded that:

Omega-3, folic acid, and coenzyme Q10 supplements represent hope for a healthy heart.
Vitamin C, vitamin E, and vitamin D supplements represent hype for a healthy heart.
β-carotene supplements represent danger for a healthy heart.

But these conclusions just scratch the surface. To put them into perspective we need to dig a bit deeper.

How Should You Interpret This Study?

In evaluating the significance of these findings there are two things to keep in mind.

#1: This study is a meta-analysis and meta-analyses have both strengths and weaknesses.

The strength of meta-analyses is that by combining multiple clinical studies they can end up with a database containing 100s of thousands of subjects. This allows them to do two things:

It allows the meta-analysis to detect statistically significant effects that might be too small to detect in an individual study.
It allows the meta-analysis to detect the average effect of all the clinical studies it includes.

The weakness of meta-analyses is that the design of individual studies included in the analysis varies greatly. The individual studies vary in things like dose, duration, type of subjects included in the study, and much more.

This is why this study rated most of their conclusions as backed by moderate- or low-quality evidence. [Note: The fact that the authors evaluated the quality of evidence is a strength of this study. Most meta-analyses just report their conclusions without telling you how strong the evidence behind those conclusions is.]

#2: Most clinical studies of supplements (including those included in this meta-analysis) have two significant weaknesses.

Most studies do not measure the nutritional status of their subjects prior to adding the supplement. If their nutritional status for a particular nutrient was already optimal, there is no reason to expect more of that nutrient to provide any benefit.
Most studies measure the effect of a supplement on a cross-section of the population without asking who would be most likely to benefit.

You would almost never design a clinical study that way if you were evaluating the effectiveness of a potential drug. So, why would you design clinical studies of supplements that way?

With these considerations in mind, let me provide some perspective on the conclusions of this study.

Coenzyme Q10:

This meta-analysis found that coenzyme Q10 significantly reduced all-cause mortality in patients with heart failure. This is consistent with multiple clinical studies and a recent Cochrane Collaboration review.

Does coenzyme Q10 have any heart health benefits for people without congestive heart failure? There is no direct evidence that it does, but let me offer an analogy with statin drugs.

Statin drugs are very effective at reducing heart attacks in high-risk patients. But they have no detectable effect on heart attacks in low-risk patients. However, this has not stopped the medical profession from recommending statins for millions of low-risk patients. The rationale is that if they are so clearly beneficial in high-risk patients, they are “probably” beneficial in low-risk patients.

I would argue a similar rationale should apply to supplements like coenzyme Q10.

Omega-3s:

This study found that omega-3 reduced both heart attacks and the risk of dying from heart disease. Most previous meta-analyses of omega-3s and heart disease have come to the same conclusion. However, some meta-analyses have failed to find any heart health benefits of omega-3s. Unfortunately, this has allowed both proponents and opponents of omega-3 use for heart health to quote studies supporting their viewpoint.

However, there is one meta-analysis that stands out from all the others. A group of 17 scientists from across the globe collaborated in developing a “best practices” experimental design protocol for assessing the effect of omega-3 supplementation on heart health. They conducted their clinical studies independently, and when their data (from 42,000 subjects) were pooled, the results showed that omega-3 supplementation decreased:

Premature death from all causes by 16%.
Premature death from heart disease by 19%.
Premature death from cancer by 15%.
Premature death from causes other than heart disease and cancer by 18%.

This study eliminates the limitations of previous meta-analyses. That makes it much stronger than the other meta-analyses. And these results are consistent with the current meta-analysis.

Omega-3s have long been recognized as essential nutrients. It is past time to set Daily Value (DV) recommendations for omega-3s. Based on the recommendations of other experts in the field, I think the DV should be set at 500-1,000 mg/day. I take more than that, but this would represent a good minimum recommendation for heart health.

Folic acid:

As with omega-3s, this meta-analysis reported a positive effect of folic acid on heart health. But many other studies have come up empty. Why is that?

It may be because, between food fortification and multivitamin use, many Americans already have sufficient blood levels of folic acid. For example, one study reported that 70% of the subjects in their study had optimal levels of folates in their blood. And that study also reported:

Subjects with adequate levels of folates in their blood received no additional benefit from folic acid supplementation.
However, for subjects with inadequate blood folate levels, folic acid supplementation decreased their risk of heart disease by ~15%.

We see this pattern over and over in supplement studies. Supplement opponents interpret these studies as showing that supplements are worthless. But a better interpretation is that supplements benefit those who need them.

The problem is that we don’t know our blood levels of essential nutrients. We don’t know which nutrients we need, and which we don’t. That’s why I like to think of supplements as “insurance” against the effects of an imperfect diet.

Vitamins E and D:

The situation with vitamins E and D is similar. This meta-analysis found no heart health benefit of either vitamin E or D. That is because the clinical studies included in the meta-analysis asked whether vitamin E or vitamin D improved heart health for everyone in the study.

Previous studies focusing on patients with low blood levels of these nutrients and/or at high risk of heart disease have shown some benefits of both vitamins at reducing heart disease risk.

So, for folic acid, vitamin E, and vitamin D (and possibly vitamin C) the take-home message should be:

Ignore all the Dr. Strangeloves telling you that these vitamins are “magic bullets” that will dramatically reduce your risk of heart disease.
Ignore the naysayers who tell you they are worthless.
Use supplementation wisely to make sure you have the recommended intake of these and other essential nutrients.

β-carotene:

This meta-analysis reported that β-carotene increased the risk of heart disease. This is not a new finding. Multiple previous studies have come to the same conclusion.

And we know why this is. There are many naturally occurring carotenoids, and they each have unique heart health benefits. A high dose β-carotene supplement interferes with the absorption of the other carotenoids. You are creating a deficiency of other heart-healthy carotenoids.

If you are not getting lots of colorful fruits and vegetables from your diet, my recommendation is to choose a supplement with all the naturally occurring carotenoids in balance – not a pure β-carotene supplement.

The Bottom Line

The Dr. Strangeloves in the nutrition space all have their favorite heart health supplements. They claim their supplements will single-handedly abolish heart disease (and help you leap tall buildings in a single bound).

On the other hand, many doctors will tell you these supplements are a waste of money. They don’t work. They just drain your wallet.

It’s so confusing. Who should you believe? Fortunately, a recent study has separated the hype from the hope and tells us which “heart-healthy” supplements work, and which don’t.

This study was a meta-analysis of 884 clinical studies with 883,627 participants. It reported:

Omega-3 supplementation deceased risk of heart attacks by 15% and all cardiovascular deaths by 7%.
Folic acid supplementation decreased stroke risk by 16%.
Coenzyme Q10 supplementation decreased the risk of all-cause mortality in patients with heart failure by 32%.
Vitamin C, vitamin E, vitamin D did not appear to affect heart disease outcomes.
β-carotene increased the risk of stroke, CVD mortality, and all-cause mortality.

For more details on this study and what it means for 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.