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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.

____________________________________________________________________________

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

___________________________________________________________________________

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 text books 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 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.

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.