Omega-3s Reduce Preterm Births

August 9, 2022 by Dr. Steve Chaney

Do Omega-3s Make For A Healthy Pregnancy?

Author: Dr. Stephen Chaney

The role of omega-3s on a healthy pregnancy has been in the news for some time. Claims have been made that omega-3s reduce preterm births, postnatal depression, and improve cognition, IQ, vision, mental focus, language, and behavior in the newborn as they grow.

The problem is that almost all these claims have been called into question by other studies. If you are pregnant or thinking of becoming pregnant, you don’t know what to believe.

Should you eat more fish?
Should you take omega-3 supplements?
Or should you just ignore the claims about omega-3s and a healthy pregnancy?

These are not trivial questions. Let’s consider preterm births as an example. The medical profession has made enormous advances in keeping premature babies alive. However, premature babies are still at higher risk of several health conditions including:

Visual impairment.
Developmental Delay.
Learning difficulties.

Plus, it is expensive to keep premature babies alive. One recent study estimated that increasing omega-3 intake during pregnancy could reduce health care costs by around $6 billion in the United Stated alone.

Unfortunately, it’s not just omega-3s and pregnancy. The same is true for almost all nutritional health claims. One day a study comes out claiming that nutrient “X” cures some disease or has some miraculous benefit. The bloggers and news media hype that study. Suddenly you see that health claim everywhere. It becomes so omnipresent that you are tempted to believe it must be true.

But wait. A few months later another study comes to opposite conclusion. Now the media is telling you that health claim is false. The months come and go, and new studies keep coming out. Some support the health claim. Others refute it.

Pretty soon the nutrition headlines just become “noise”. You don’t know what to believe. If you want the truth, “Who ya gonna call?”

Who Ya Gonna Call?

It’s not Ghostbusters. It not Dr. Strangelove’s health blog. It’s a group called the Cochrane Collaboration.

The Cochrane Collaboration consists of 30,000 volunteer scientific experts from across the globe whose sole mission is to analyze the scientific literature and publish reviews of health claims so that health professionals, patients, and policy makers can make evidence-based choices about health interventions.

The Cochrane Collaboration reviews all the relevant studies on a topic, exclude those that are biased or weak, and make their recommendations based on only the strongest studies. Their reviews are considered the gold standard of evidence-based medicine.

If you are of a certain age, you may remember that TV commercial “When EF Hutton talks, people listen.” It is the same with the Cochrane Collaboration. When they talk, health professionals listen.

This week we will examine the Cochrane Collaboration’s review titled “Omega-3 Fatty Acid Addition During Pregnancy”.

How Was The Study Done?

For this analysis the Cochrane Collaboration reviewed 70 randomized controlled trials which compared the effect of added omega-3s on pregnancy outcomes with either a placebo or a diet no added omega-3s. These trials included almost 19,927 pregnant women.

In one sense, Cochrane reviews are what is called a “meta-analysis”, in which data from numerous studies are grouped together so that a statistically significant conclusion can be reached. However, Cochrane Collaboration reviews differ from most meta-analyses found in the scientific literature in a very significant way.

Many published meta-analyses simply report “statistically significant” conclusions. However, statistics can be misleading. As Mark Twain said: “There are lies. There are damn lies. And then there are statistics”.

The problem is that the authors of most meta-analyses group studies together without considering the quality of studies included in their analysis. This creates a “Garbage In – Garbage Out” effect. If the quality of individual studies is low, the quality of the meta-analysis will also be low. Simply put, the conclusions from some published meta-analyses are not worth the paper they are written on.

The Cochrane Collaboration also reports statistically significant conclusions from their meta-analyses. However, they also carefully consider the quality of each individual study in their analysis. They look at possible sources of bias. They look at the design and size of the studies. Finally, they ask whether the conclusions are consistent from one study to the next. They clearly define the quality of evidence that backs up each of their conclusions as follows:

High-quality evidence. Further research is unlikely to change their conclusion. This is generally reserved for conclusions backed by multiple high-quality studies that have all come to the same conclusion. These are the recommendations that are most often adopted into medical practice.

Moderate-quality evidence. This conclusion is likely to be true, but further research could have an impact on it.

Low-quality evidence. Further research is needed and could alter the conclusion. They are not judging whether the conclusion is true or false. They are simply saying more research is needed to reach a definite conclusion.

Omega-3s Reduce Preterm Births

Here are the conclusions that the Cochrane Collaboration said were supported by high-quality evidence:

Omega-3s reduce the risk of preterm births.

Omega-3s reduce the risk of low-birth-weight infants.

The authors concluded: “Omega-3 supplementation during pregnancy is an effective strategy for reducing the risk of preterm birth…More studies comparing omega-3s and placebo are not needed at this point.”

In other words, they are saying this conclusion is definite. Omega-3 supplementation should become part of the standard of medical care for pregnant women.

However, they did say that further studies were needed “…to establish if, and how, outcomes vary by different types of omega-3s, timing [stage of pregnancy], doses [of omega-3s], or by characteristics of women.”

That’s because these variables were not analyzed in the Cochrane study. Their review and meta-analysis included clinical trials:

Of women at low, moderate, and high risk of poor pregnancy outcomes.

With DHA alone, with EPA alone, and with a mixture of both.

Omega-3 doses that were low (˂ 500 mg/day), moderate (500-1,000 mg/day), and high (> 1,000 mg/day).

Do Omega-3s Make For A Healthy Pregnancy?

What about the effect of omega-3s on other pregnancy outcomes?

The conclusions the Cochrane Collaboration said were supported by moderate quality evidence included reductions in:

Perinatal death.

Admissions to the neonatal intensive care unit.

There was not enough high or moderate quality data to determine the effect of omega-3s on other pregnancy outcomes such as postnatal depression. More research is still needed in those areas. However, if you do receive any of these benefits from omega-3 supplementation, you can just consider them as side benefits.

What Does This Report Mean For You?

1) The proven effect of omega-3 supplementation on preterm births is significant because preterm births increase the risk of:

Visual impairment.
Developmental Delay.
Learning difficulties.

2) The likely effect of omega-3s on admission to neonatal intensive care units is significant because those units are very expensive.

3) The Cochrane study did not determine whether omega-3 supplementation was equally important for women at low, moderate, and high likelihood of poor pregnancy outcomes.

Therefore, omega-3 supplementation should be considered for all pregnant women.

4) The Cochrane study did not determine whether omega-3 supplementation was equally important during the first, second, or third trimester.

Therefore, omega-3 supplementation should be considered by all women of childbearing age who might become pregnant and throughout pregnancy.

5) The Cochrane study did not determine whether DHA, EPA, or a mixture of the two was most effective.

Therefore, your omega-3 supplement should probably contain both DHA and EPA. A group of experts recently recommended that adults consume at least 650 mg/day of omega-3s with ≥ 220 mg of that coming from DHA and ≥ 220 mg/day coming from EPA.

Since most pregnant women in this country consume around 89 mg/day of DHA + EPA, omega-3 supplementation is warranted.

The Bottom Line

The effect of omega-3s on pregnancy outcomes have been confusing. Some studies conclude that omega-3s are important for a healthy pregnancy. Other studies suggest they are ineffective. What are you to believe?

Fortunately, a group called the Cochrane Collaboration recently conducted a comprehensive review of this topic. This is significant because Cochrane Reviews are internationally recognized as the highest standard in evidence-based health care. They influence the treatment protocols recommended by the medical community.

This Cochrane Review concluded that omega-3 supplementation during pregnancy:

Reduces preterm births and low birth weight infants.

Likely reduces perinatal death and admissions to the neonatal intensive care unit.

The authors of the review said: “Omega-3 supplementation during pregnancy is an effective strategy for reducing the risk of preterm birth…More studies comparing omega-3s and placebo are not needed at this point.”

In other words, they are saying this conclusion is definite. Omega-3 supplementation should become part of the standard of medical care for pregnant women.

For more details on 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.

How Much Omega-3 Should You Take During Pregnancy?

June 22, 2021 by Dr. Steve Chaney

Which Omega-3s Are Beneficial?

Author: Dr. Stephen Chaney

Preterm births (births occurring before 37 weeks) are increasing in this country. Just between 2018 and 2019, the percentage of preterm births increased by 2% to over 10% of all pregnancies. That is a concern because preterm births are associated with an increased risk of:

Visual impairment.
Developmental delays.
Learning difficulties.
Problems with normal development of lungs, eyes, and other organs.

Plus, it is expensive to keep premature babies alive. One recent study estimated that reducing the incidence of preterm births by around 50% could reduce health care costs by $6 billion in the United Stated alone.

Of the 10% preterm births, 2.75% of them are early preterm births (births occurring before 34 weeks). Obviously, the risk of health problems and the cost of keeping them alive is greatest for early preterm babies.

We don’t know why preterm births are increasing, but some experts feel it is because in this country:

More older women are having babies.

There is increased use of fertility drugs, resulting in multiple babies

Unfortunately, there is no medical standard for identifying pregnancies at risk for preterm birth. Nor is there any agreement around prevention measures for preterm births.

However, recent research has suggested that some premature births may be caused by inadequate omega-3 status in the mother and can be prevented by omega-3 supplementation.

What Do We Know About Omega-3s And Risk Of Preterm Births?

The problem is that almost all these claims have been called into question by other studies. If you are pregnant or thinking of becoming pregnant, you don’t know what to believe.

Fortunately, a group called the Cochrane Collaboration has recently reviewed these studies. The Cochrane Collaboration consists of 30,000 volunteer scientific experts from across the globe whose sole mission is to analyze the scientific literature and publish reviews of health claims so that health professionals, patients, and policy makers can make evidence-based choices about health interventions. Their reviews are considered the gold standard of evidence-based medicine.

This is because most published meta-analyses simply report “statistically significant” conclusions. However, statistics can be misleading. As Mark Twain said: “There are lies. There are damn lies. And then there are statistics”.

The problem is the authors of most meta-analyses group studies together without considering the quality of studies included in their analysis. This creates a “Garbage In – Garbage Out” effect. If the quality of individual studies is low, the quality of the meta-analysis will also be low.

The Cochrane Collaboration reviews are different. They also report statistically significant conclusions from their meta-analyses. However, they carefully consider the quality of each individual study in their analysis. They look at possible sources of bias. They look at the design and size of the studies. Finally, they ask whether the conclusions are consistent from one study to the next. They clearly define the quality of evidence that backs up each of their conclusions.

For omega-3s and pregnancy, the Cochrane Collaboration performed a meta-analysis and review of 70 randomized controlled trials that compared the effect of added omega-3s on pregnancy outcomes with the effect of either a placebo or no omega-3s. These trials included almost 19,927 pregnant women.

This Cochrane Collaboration Review looked at all the claims for omega-3s and pregnancy outcome, but they concluded that only two of the claims were supported by high-quality evidence:

Omega-3s reduce the risk of preterm births.

Omega-3s reduce the risk of low birth-weight infants.

The authors concluded: “Omega-3 supplementation during pregnancy is an effective strategy for reducing the risk of preterm birth…More studies comparing [the effect of] omega-3s and placebo [on preterm births] are not needed at this point.”

In other words, they are saying this conclusion is definite. The Cochrane Collaboration has declared that omega-3 supplementation should become part of the standard of medical care for pregnant women.

However, the Cochrane Collaboration did say that further studies were needed “…to establish if, and how, outcomes vary by different types of omega-3s, timing [stage of pregnancy], doses [of omega-3s], or by characteristics of women.”

That’s because these variables were not analyzed in this study. The study included clinical trials:

Of women at low, moderate, and high risk of poor pregnancy outcomes.

With DHA alone, with EPA alone, and with a mixture of both.

Omega-3 doses that were low (˂ 500 mg/day), moderate (500-1,000 mg/day), and high (> 1,000 mg/day).

I have discussed these findings in more detail in a previous issue of “Health Tips From The Professor”

How Was This Study Done?

The current study (SE Carlson et al, EClinicalMedicine, 2021) is a first step towards answering those questions.

The authors of this study focused on how much DHA supplementation is optimal during pregnancy. This is an important question because there is currently great uncertainty about how much DHA is optimal:

The American College of Obstetrics and Gynecology recommends supplementation with 200 mg/day of DHA. However, that recommendation assumes that the increase will come from fish and was influenced by concerns that omega-3-rich fish are highly contaminated with heavy metals and PCBs.

Another group of experts was recently asked to develop guidelines for omega-3 supplementation during pregnancy. They recommended pregnant women consume at least 300 mg/day of DHA and 220 mg/day of EPA.

The WHO has recommended of minimum dose of 1,000 mg of DHA during pregnancy.

Many prenatal supplements now contain 200 mg of DHA, but very few provide more than 200 mg.

Accordingly, the authors took the highest and lowest recommendations for DHA supplementation and asked whether 1,000 mg of DHA per day was more effective than 200 mg of DHA at reducing the risk of early preterm births. Their hypothesis was that 1,000 mg of DHA would be more effective than 200 mg/day at preventing early preterm births.

This study was a multicenter, double-blind, randomized trial of 1032 women recruited at one of three large academic medical centers in the United States (University of Kansa, Ohio State University, and University of Cincinnati).

The women were ≥ 18 years old (average age = 30) and between 12 and 20 weeks of gestation when they entered the study.

The breakdown by ethnicity was 50% White, 22% Black or African American, 22% Hispanic, 6% Other.

18% had a prior preterm birth (<37 weeks) and 7% had a prior early preterm birth (<34 weeks).

Prior to enrollment in the study 47% of the participants reported taking a DHA supplement and 19% of the participants took a DHA supplement with > 200 mg/day.

All the participants received 200 mg DHA capsules and were told to take one capsule daily. The participants were also randomly assigned to take 2 additional capsules that contained a mixture of corn and soybean oil (the 200 mg DHA/day group) or 2 capsules that contained 400 mg of DHA (the 1,000 mg DHA/day group). The capsules were orange flavored so the participants could not distinguish between the DHA capsules and the placebo capsules.

Blood samples were drawn upon entry to the study and either just prior to delivery or the day after delivery to determine maternal DHA status.

The study was designed to look at the effect of DHA dose (1,000 mg or 200 mg) on early preterm birth (<34 weeks), preterm birth (<37 weeks), low birth weight (< 3 pounds), and several other parameters related to maternal and neonatal health.

How Much Omega-3 Should You Take During Pregnancy?

The primary findings from this study were:

The rate of early preterm births (<34 weeks) was less (1.7%) for pregnant women taking 1,000 mg of DHA/day compared to 200 mg/day (2.4%).

The rate of late preterm births (between 34 and 37 weeks) was also less for women taking 1,000 mg of DHA/day compared to 200 mg/day.

Finally, low birth weight and the frequency of several maternal and neonatal complications during pregnancy, delivery, and immediately after delivery were also lower with 1,000 mg/day of supplemental DHA than with 200 mg/day.

This confirms the authors’ hypothesis that supplementation with 1,000 mg/day of DHA is more effective than 200 mg/day at reducing the risk of early preterm births. In addition, this study showed that supplementation with 1,000 mg of DHA/day had additional benefits.

This study did not have a control group receiving no DHA. However:

The US average for early preterm births is 2.74%.

For the women in this study who had previous pregnancies, the rate of early preterm birth was 7%.

Of course, the important question for any study of this type is whether all the women benefited equally from supplementation. Fortunately, this study was designed to answer that question.

As noted above, each woman was asked whether they took any DHA supplements at the time they enrolled in the study, and 47% of the women in the study were taking DHA supplements when they enrolled. In addition, the DHA status of each participant was determined from blood samples taken at the time the women were enrolled in the study. When the authors split the women into groups based on their DHA status at the beginning of the study:

For women with low DHA status the rate of early preterm births was 2.0% at 1,000 mg of DHA/day versus 4.1% at 200 mg of DHA/day.

For women with high DHA status the rate of early preterm births was around 1% for both 1,000 mg of DHA/day and 200 mg of DHA/day.

In other words, DHA supplementation only appeared to help women with low DHA status. This is good news because:

DHA status is an easy to measure predictor of women who are at increased risk of early preterm birth.

This study shows that supplementation with 1,000 mg of DHA/day is effective at reducing the risk of early premature birth for women who are DHA deficient.

In the words of the authors, “Clinicians could consider prescribing 1,000 mg DHA daily during pregnancy to reduce early preterm birth in women with low DHA status if they are able to screen for DHA.”

Which Omega-3s Are Beneficial?

DHA is the most frequently recommended omega-3 supplement during pregnancy.

It is not difficult to understand why that is.

DHA is a major component of the myelin sheath that coats every neuron in the brain. [You can think of the myelin sheath as analogous to the plastic coating on a copper wire that allows it to transmit electricity from one end of the wire to the other.]

Unlike other components of the myelin sheath, the body cannot make DHA. It must be provided by the diet.

During the third trimester, DHA accumulates in the human brain faster than any other fatty acid.

Animal studies show that DHA deficiency during pregnancy interferes with normal brain and eye development.

Some, but not all, human clinical trials show that DHA supplementation during pregnancy improves developmental and cognitive outcomes in the newborn.

Recent studies have shown that most women in the United States only get 60-90 mg/day of DHA in their diet.

Clearly, DHA is important for fetal brain development during pregnancy, and most pregnant women are not getting enough DHA in their diet. This is why most experts recommend supplementation with DHA during pregnancy. And this study suggests supplementation with 1,000 mg/day is better than 200 mg/day. However, two important questions remain:

#1: Is 1,000 mg of DHA/day optimal? The answer is, “We don’t know”. This study compared the highest recommended dose (1,000 mg/day) with the lowest recommended dose (200mg/day) and concluded that 1,000 mg/day was better than 200 mg/day.

But would 500 or 800 mg/day be just as good as 1,000 mg/day? We don’t know. More studies are needed.

#2: Can DHA do it all, or are other omega-3s also important for a healthy pregnancy? As noted above, the emphasis on supplementation with DHA was based on the evidence for a role of DHA in fetal brain development during pregnancy.

But is DHA or EPA more effective at preventing early preterm birth and maternal pregnancy complications? Again, we don’t know.

As noted above, the Cochrane Collaboration concluded that omega-3s were effective at reducing early preterm births but was unable to evaluate the relative effectiveness of EPA and DHA because their review included studies with DHA only, EPA only, and EPA + DHA.

This is an important question because the ability of the body to convert EPA to DHA and vice versa is limited (in the 10-20%) range. This means that if both EPA and DHA are important for a healthy pregnancy, it might not be optimal to supplement with a pure DHA or pure EPA supplement.

Based on currently available data if you are pregnant or thinking of becoming pregnant, my recommendations are:

Chose a supplement that provides both EPA and DHA.

Because the evidence is strongest for DHA at this time, chose an algal source of omega-3s that has more DHA than EPA.

Aim for a dose of DHA in the 500 mg/day to 1,000 mg/day range. Remember, this study showed 1,000 mg/day was better than 200 mg/day but did not test whether 500 or 800 mg/day might have been just as good.

As more data become available, I will update my recommendations.

The Bottom Line

The Cochrane Collaboration recently released a report saying that the evidence was definitive that omega-3 supplementation during pregnancy reduced the risk of early preterm births. However, they were not able to reach a definitive conclusion on the optimal dose of omega-3s or the relative importance of EPA and DHA at preventing early preterm birth.

Most experts recommend that pregnant women supplement with between 200 mg/day and 1,000 mg/day of DHA.

A recent study asked whether 1,000 mg of DHA/day was better than 200 mg/day at reducing the risk of early preterm birth. The study found:

The rate of early preterm births (<34 weeks) was less (1.7%) for pregnant women taking 1,000 mg of DHA/day than pregnant women taking 200 mg/day (2.4%).

For women with low DHA status at the beginning of the study, the rate of early preterm births was 2.0% at 1,000 mg of DHA/day versus 4.1% at 200 mg of DHA/day.

For women with high DHA status at the beginning of the study, the rate of early preterm births was around 1% for both 1,000 mg of DHA/day and 200 mg of DHA/day.

The authors concluded, “Clinicians could consider prescribing 1,000 mg DHA daily during pregnancy to reduce early preterm birth in women with low DHA status…”

There are two important caveats:

This study did not establish the optimal dose of DHA. The study concluded that 1,000 mg/day was better than 200 mg/day. But would 500 or 800 mg/day be just as good as 1,000 mg/day? We don’t know. More studies are needed.

This study did not establish the relative importance of EPA and DHA for reducing the risk of early preterm births. DHA is recommended for pregnant women based on its importance for fetal brain development. But is DHA more important than EPA for reducing the risk of early preterm births? Again, we don’t know. More studies are needed.

For more details about this study and my recommendations, 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.

Do Omega-3s Add Years To Your Life?

June 1, 2021 by Dr. Steve Chaney

Why Are Omega-3s So Controversial?

Author: Dr. Stephen Chaney

I don’t need to tell you that omega-3s are controversial. Some experts confidently tell you that omega-3s significantly reduce your risk of heart disease and may reduce your risk of cancer and other diseases. Other experts confidently tell you that omega-3s have no effect on heart disease or any other disease. They claim that omega-3 supplements are no better than “snake oil”.

The problem is that each camp of experts can cite published clinical studies to support their claims. How can that be? How can clinical studies come to opposite conclusions on such an important topic? The problem is that it is really difficult to do high quality clinical studies on omega-3s. I will discuss that in the next section.

The question of whether omega-3s affect life span has also been controversial. Heart disease and cancer are the top two causes of death in this country. So, if omega-3s actually reduced the risk of heart disease and cancer, you might expect that they would also help us live longer. Once again, there are studies on both sides of this issue, but they are poor quality studies.

We need more high-quality studies to clear up the controversies surrounding the health benefits of omega-3s. I will report on one such study in this issue of “Health Tips From The Professor”. But first let me go into more depth about why it is so difficult to do high-quality studies with omega-3 fatty acids.

Clinical Studies 101: Why Are Omega-3s So Controversial?

I have covered this topic in previous issues of “Health Tips From the Professor”, but here is a quick summary.

Randomized, placebo controlled clinical trials (RCTs) are considered the gold standard for evidence-based medicine, but they ill-suited to measure the effect of omega-3s on health outcomes.

- Heart disease and cancer take decades to develop. Most RCTs are too small and too short to show a meaningful effect of omega-3s on these diseases.

- To make up for this shortcoming, some recent RCTs have started with older, sicker patients. This way enough patients die during the study that it can measure statistically significant outcomes. However, these patients are already on multiple medications that mimic many of the beneficial effects of omega-3s on heart disease.

These studies are no longer asking whether omega-3s reduce the risk of heart disease. They are really asking if omega-3s have any additional benefits for patients who are already taking multiple medications – with all their side effects. I don’t know about you, but that is not the question I am interested in.

- Until recently, most RCTs did not measure circulating omega-3 levels before and after supplementation, so the investigators had no idea whether omega-3 supplementation increased circulating omega-3 levels by a significant amount.

And for the few studies where omega-3 levels were measured before and after supplementation, it turns out that for many of the participants, their baseline omega-3 levels were too high for omega-3 supplementation to have a meaningful effect. Only participants with low omega-3 levels at the beginning of the study benefited from omega-3 supplementation.

These studies are often quoted as showing omega-3 supplementation doesn’t work. However, they are actually showing the true value of supplementation. Omega-3 supplementation isn’t for everyone. It is for people with poor diet, increased need, genetic predisposition, and/or pre-existing disease not already treated with multiple medications.

2) Prospective cohort studies eliminate many of the shortcomings of RCTs. They can start with a large group of individuals (a cohort) and follow them for many years to see how many of them die or develop a disease during that time (this is the prospective part of a prospective cohort trial). This means they can start with a healthy population that is not on medications.

This also means that these studies can answer the question on most people’s minds, “Are omega-3s associated with reduced risk of dying or developing heart disease?” However, these studies have two limitations.

- They are association studies. They cannot measure cause and effect.

- Ideally, omega-3 levels would be measured at the beginning of the study and at several intervals during the study to see if the participant’s diet had changed during the study. Unfortunately, most prospective cohort studies only measure omega-3 levels at the beginning of the study.

3) Finally, a meta-analysis combines data from multiple clinical studies.

- The strength of a meta-analysis is that the number of participants is quite large. This increases the statistical power and allows it to accurately assess small effects.

- The greatest weakness of meta-analyses is that the design of the individual studies included in the meta-analysis is often quite different. This introduces variations that decrease the reliability of the meta-analysis. It becomes a situation of “Garbage in. Garbage out”

The study (WS Harris et al, Nature Communications, Volume 12, Article number: 2329, 2021) I am discussing today is a meta-analysis of prospective cohort studies. It was designed to determine the association between blood omega-3 fatty acids and the risk of:

Death from all causes.
Death from heart disease.
Death from cancer.
Death from causes other than heart disease or cancer.

More importantly, it eliminated the major weakness of previous meta-analyses by only including studies with a similar design.

How Was This Study Done?

This study was a meta-analysis of 17 prospective cohort studies with a total of 42,466 individuals looking at the association between omega-3 fatty acid levels in the blood and premature death due to all causes, heart disease, cancer, and causes other than heart disease and cancer.

Participants in the 17 studies were followed for an average of 16 years, during which time 15,720 deaths occurred. This was a large enough number of deaths so that a very precise statistical analysis of the data could be performed.

The average age of participants at entry into the studies was 65, and 55% of the participants were women. Whites constituted 87% of the participants, so the results may not be applicable to other ethnic groups. None of the participants had heart disease or cancer when they entered the study.

Finally, the associations were corrected for a long list of variables that could have influenced the outcome (Read the publication for more details).

A strength of this meta-analysis is that all 17 studies were conducted as part of the FORCE (Fatty Acids & Outcomes Research Consortium) collaboration. The FORCE collaboration was established with the goal of understanding the relationships between fatty acids (as measured by blood levels of the omega-3 fatty acids) on premature death and chronic disease outcomes (cardiovascular disease, cancer, and other conditions).

Each study was designed using a standardized protocol, so that the data could be easily pooled for a meta-analysis. In the words of the FORCE collaboration founders:

The larger sample sizes of [meta-analyses] will substantially increase statistical power to investigate associations…enabling the [meta-analyses] to discover important relationships not discernible in any individual study.

2) Standardization of variable definitions and modeling of associations will reduce variation and potential bias in estimates across cohorts.

3) Results will be far less susceptible to publication bias.

Do Omega-3s Add Years To Your Life?

The meta-analysis divided participants into quintiles based on blood omega-3 levels. When comparing participants with the highest omega-3 levels with participants with the lowest omega-3 levels:

Premature death from all causes was decreased by 16%.

- When looking at the effect of individual omega-3s, EPA > EPA+DHA > DHA.

Premature death from heart disease was decreased by 19%.

- When looking at the effect of individual omega-3s, DHA > EPA+DHA > EPA.

Premature death from cancer was decreased by 15%.

- When looking at the effect of individual omega-3s, EPA > DHA > EPA+DHA.

Premature death from causes other than heart disease and cancer was decreased by 18%.

- When looking at the effect of individual omega-3s, EPA > EPA+DHA > DHA.

The differences between the effects of EPA, DHA, and EPA+DHA were small.

ALA, a short chain omega-3 found in plant foods, had no effect on any of these parameters.

In the words of the authors: “These findings suggest that higher circulating levels of long chain omega-3 fatty acids are associated with a lower risk of premature death. Similar relationships were seen for death from heart disease, cancer, and causes other than heart disease and cancer. No associations were seen with the short chain omega-3, ALA [which is found in plant foods]”.

What Does This Study Mean For You?

If you are thinking that 15-19% decreases in premature death from various causes don’t sound like much, let me do some simple calculations for you. The average lifespan in this country is 78 years.

A 16% decrease in death from all causes amounts to an extra 12.5 years. What would you do with an extra 12.5 years?

A 19% decrease in death from heart disease might not only allow you to live longer, but it has the potential to improve your quality of life by living an extra 15 years free of heart disease.

Similarly, a 15% decrease in death from cancer might help you live an extra 12 years cancer-free.

In other words, you may live longer, and you may also live healthier longer, sometimes referred to as “healthspan”.

Don’t misunderstand me. Omega-3s are not a magic wand. They aren’t the fictional “Fountain of Youth”.

There are many other factors that go into a healthy lifestyle. If you sit on your couch all day eating Big Macs and drinking beer, you may be adding the +12.5 years to a baseline of -30 years.

Clinical studies report average values and none of us are average. Omega-3s will help some people more than others.

I will understand if you are skeptical. It seems like every time one study comes along and tells you that omega-3s are beneficial, another study comes along and tells you they are worthless.

This was an extraordinarily well-designed study, but it is unlikely to be the final word in the omega-3 controversy. There are too many poor-quality studies published each year. Until everyone in the field agrees to some common standards like those in the FORCE collaboration, the omega-3 controversy will continue.

The Bottom Line

A recent meta-analysis looked at the association between omega-3 fatty acid levels in the blood and premature death due to all causes, heart disease, cancer, and causes other than heart disease and cancer.

The meta-analysis divided participants into quintiles based on blood omega-3 levels. When comparing participants with the highest omega-3 levels with participants with the lowest omega-3 levels:

Premature death from all causes was decreased by 16%.

Premature death from heart disease was decreased by 19%.

Premature death from cancer was decreased by 15%.

Premature death from causes other than heart disease and cancer was decreased by 18%.

For more details about study and what this study 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.

Update On Omega-3 Supplementation And Heart Disease

November 10, 2020 by Dr. Steve Chaney

How Much Omega-3s Do You Need?

In previous issues of “Health Tips From The Professor” I have described the medical consensus about omega-3 supplementation and heart disease as resembling a pendulum.

A few positive studies are published, and the pendulum swings in the positive direction. The medical consensus becomes, “Omega-3s may reduce heart disease risk.”

Then a few negative studies are published, and the pendulum swings in the other direction. The consensus becomes that omega-3 supplements are worthless. One review a few years ago went so far as to say that fish oil supplements were the modern-day version of snake oil.

Meta-analyses combine the data from multiple clinical studies to increase statistic power and minimize the effect of clinical studies that are outliers. They are supposed to provide clear answers to medical questions like the effect of omega-3 supplements on heart disease.

However, the meta-analyses published to date have also reached conflicting conclusions about the effectiveness of omega-3 supplementation. No wonder you [and the medical community] are confused!

In 2018 three large, well-designed, clinical studies looking at the effect of omega-3 supplementation on heart disease risk were published. They reached different conclusions. However, they covered a much wider range of omega-3 doses than previous studies. And the studies with the highest doses of omega-3s showed the most positive effect of omega-3 supplementation on the reduction of heart disease risk.

That lead a group of doctors and scientists from the United States and Finland to postulate that many previous studies had failed to find an effect of omega-3 supplements on heart disease risk because the dose of omega-3s they used was too low.

These scientists designed a very large meta-analysis (AA Bernasconi et al, Mayo Clinic Proceedings, doi.org/10.1016/j.mayocp.2020.08.034) to test their hypothesis. In short, their study was designed to:

Determine whether supplementation with the omega-3 fatty acids EPA and DHA resulted in reduced heart disease risk.

Quantify the relationship between the dose of EPA + DHA and the risk of heart disease outcomes.

How Was The Study Done?

This study was a meta-analysis of 40 randomized control clinical studies on the effect omega-3 supplementation on heart disease outcomes. Specifically:

It included all high-quality clinical studies of omega-3 supplementation published before August 2019.

It included a total of 135,267 participants.

It included participants at both low and high risk of developing heart disease.

It included studies of supplementation with EPA alone and with EPA + DHA.

It included omega-3 doses ranging from 400 mg/day to 5,500 mg/day.

It excluded dietary studies because:

- It is difficult to measure the dosage of omega-3s that participants are consuming in dietary studies.

- It is difficult to assure their compliance with dietary advice.

- There is variation in the omega-3 content of various foods.

- Participants in these studies are often advised to make other changes in diet. It then becomes difficult to know whether any benefits observed were from changes in omega-3s or from changes in other components of the diet.

Update On Omega-3 Supplementation And Heart Disease

Here are the results of the meta-analysis. Supplementation with EPA or EPA + DHA reduced:

Coronary Heart disease (defined as diseases caused by atherosclerosis, such as angina, heart attack, and heart failure) by 10%.

Heart Attacks by 13%.

Coronary Heart disease deaths by 9%.

Heart attack deaths by 35%.

Because of the large number of participants in this meta-analysis, they were able to reach some other important conclusions:

Despite the claims you may have heard about a new drug consisting of highly purified EPA, this study found no evidence that EPA supplementation was superior to EPA + DHA supplementation.

Even though heart medications provide some of the same benefits as omega-3s, this study concluded that omega-3 supplementation reduced the risk of heart disease even for patients on multiple heart medications.

This study also concluded that omega-3 supplementation was likely to be effective for people at both low and high risk of heart disease. This means that omega-3 supplementation is likely to be beneficial for preventing heart disease.

The authors concluded: “The current study provides strong evidence that EPA + DHA supplementation is an effective strategy for the prevention of certain coronary heart disease outcomes…Considering the relatively low costs and side effect profiles of omega-3 supplementation and the low drug-drug interactions with other standard therapies…clinicians and patients should consider the potential benefits of omega-3 (EPA/DHA) supplementation…”

What Does This Study Mean For You?

The most significant conclusions from this study are the reduction in heart attacks and heart attack deaths. That is because:

Approximately 1.5 million Americans suffer a heart attack each year. For those who survive their quality of life may be permanently altered.

- A 13% reduction in heart attacks means that something as simple as EPA + DHA supplementation might prevent as many as 195,000 heart attacks a year.

Approximately 100,000 Americans will die from a heart attack each you.

- A 35% reduction in heart attack deaths means that EPA + DHA supplementation might prevent as many as 35,000 deaths from heart attacks each year.

For many Americans sudden death from a heart attack is the first indication that they have heart disease.

- As Benjamin Franklin said, “An ounce of prevention is worth a pound of cure”. That is why EPA + DHA supplementation makes sense for most people.

I can’t say that this study will be the final word on omega-3 supplementation and heart disease risk. However, several recent studies have supported the benefit of omega-3 supplementation at reducing heart disease risk. The pendulum has clearly swung in the direction of omega-3s being beneficial for heart health.

Of course, omega-3 supplementation is not a magic “Get Out of Jail Free” card. You can’t expect it to overcome the effects of a bad diet and lack of exercise with omega-3 supplementation alone. You need a holistic approach.

The American Heart Association recommends:

If you smoke, stop.

Choose good nutrition.

- Choose a diet that emphasizes vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, non-tropical vegetable oils, and nuts.

- Choose a diet that limits sweets, sugar-sweetened beverages, and red meats.

Reduce high blood cholesterol and triglycerides.

Reduce your intake of saturated fat, trans fat and cholesterol and get moving.

Lower High Blood Pressure.

Be physically active every day.

- Aim for at least 150 minutes per week of moderate-intensity physical activity per week.

Aim for a healthy weight.

Manage diabetes.

Reduce stress.

Limit alcohol.

Have a regular physical checkup.

Add in omega-3 supplementation to these recommendations and you have a winning combination.

How Much Omega-3s Do You Need?

As I mentioned at the beginning of this article the omega-3 dosages used in the studies included in this meta-analysis ranged from 400 mg/day to 5,500 mg/day. More importantly, there were enough participants in these studies to obtain a fairly accurate estimate of dose response. This allow the authors to answer the question, “How much omega-3s do I need?”The study found that:

The protective effect of omega-3s for heart attack deaths and coronary heart disease deaths plateaued with dosages of EPA + DHA that exceeded 800 – 1200 mg/day.

The dose response of the protective effect of omega-3s for non-fatal heart attacks was linear over a wider range of dosages, with every increase 1,000 mg/day of EPA + DHA decreasing the risk of heart attack by 9%.

Based on the totality of their data, the authors concluded, “…clinicians and patients should consider the potential benefits of omega-3 supplementation, especially using 1,000 to 2,000 mg/day dosages, which are rarely obtained in most Westernized diets, even those including routine fish consumption.”

The Bottom Line

A recent meta-analysis combined the data from 40 clinical studies with over 135,000 participants looking at the effect of omega-3 supplementation on various types of heart disease. The study found that supplementation with EPA or EPA + DHA reduced:

Coronary Heart disease (defined as diseases caused by atherosclerosis, such as angina, heart attack, and heart failure) by 10%.

Heart Attacks by 13%.

Coronary Heart disease deaths by 9%.

Heart attack deaths by 35%.

Because of the large number of participants in this meta-analysis, they were able to reach some other important conclusions:

This study found no evidence that EPA supplementation was superior to EPA + DHA supplementation.

This study concluded that omega-3 supplementation reduced the risk of heart disease even for patients on multiple heart medications.

This study also concluded that omega-3 supplementation was likely to be effective for people at both low and high risk of heart disease. This means that omega-3 supplementation is likely to be beneficial for preventing heart disease.

The optimal dose of EPA + DHA appeared to be 1,000 – 2,000 mg/day.

The authors of the study concluded: “The current study provides strong evidence that EPA + DHA supplementation is an effective strategy for the prevention of certain coronary heart disease outcomes…Considering the relatively low costs and side effect profiles of omega-3 supplementation and the low drug-drug interactions with other standard therapies…clinicians and patients should consider the potential benefits of omega-3 (EPA/DHA) supplementation, especially using 1,000 to 2,000 mg/day dosages, which are rarely obtained in most Westernized diets, even those including routine fish consumption.”

For more details, including a more detailed discussion of what this study 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.

How Much DHA Is Needed To Prevent Alzheimer’s

September 8, 2020 by Dr. Steve Chaney

What Are We Missing?

We are an aging population. As such, issues like cognitive decline, dementia, and Alzheimer’s Disease are of increasing concern. After all, what is the good of reaching your “Golden Years” with a healthy body if you lose your mind?

The ability of the omega-3 fatty acids DHA and EPA to reduce the risk of cognitive decline, dementia, and Alzheimer’s Disease is controversial. Some studies say yes. Others say no.

When studies are conflicting most experts simply conclude the treatment is unproven. I am sympathetic to that viewpoint, but I first like to ask the questions: “Why are the studies conflicting? What are we missing?”

I start by evaluating the strengths and weaknesses of the individual studies.

If the studies claiming the treatment works are weak, I am content to “join the chorus” and consider the treatment unproven.

If the studies claiming the treatment doesn’t work are weak, I am a strong advocate for more well-designed studies before we conclude that the treatment doesn’t work.

If both the “pro” and “con” studies are strong, I want to ask, “What are we missing?”

This is the situation with studies asking whether DHA reduces the risk of Alzheimer’s Disease and other forms of cognitive decline as we age.

Association studies show that greater intake and higher blood levels of the omega-3 fatty acids EPA and DHA are associated with lower risk of Alzheimer’s Disease.

However, most placebo-controlled clinical trials with either DHA alone or DHA + EPA have come up negative. Of course, one can always argue that most of the placebo-controlled clinical trials were too short or too small to show a statistically significant effect. But, my question remains, “What else are we missing?”

One recent study has provided an interesting clue. The authors of the study postulated that B vitamins were required to deliver omega-3 fatty acids to the brain, and their study showed that omega-3 fatty acids were only effective at decreasing the risk of cognitive decline in subjects who also had optimal B vitamin status.

In other words, this study suggested that studies on the effect of omega-3 supplementation and risk of developing Alzheimer’s are doomed to failure if a significant percentage of the subjects have sub-optimal B vitamin status.

The authors of the current study ( IC Arellanes et al, EBioMedicine, doi.org/10.1016/j.ebiom.2020.102883) proposed two additional hypotheses for the negative results of previous clinical trials and designed an experiment to test their hypotheses. Their hypotheses were:

Uptake of DHA and EPA by the brain is very inefficient, and previous studies have not used sufficient doses of DHA or DHA plus EPA to see a significant effect on cognitive impairment.

The APOE4 gene further decreases the uptake of DHA and EPA by the brain.

Before I describe how the study was done, I should probably provide some context by describing how DHA and EPA reach the brain and the role of the apoE protein in the process. It’s time for my favorite topic: “Biochemistry 101”.

Biochemistry 101: What Does The ApoE Protein Do?

If you have ever tried to mix oil and water, it should come as no surprise to you that fats, including DHA and EPA, and cholesterol are not water soluble. That leaves our bodies with a dilemma. How do they get the fat and cholesterol we eat to pass through our bloodstream and get to our cells, where they are needed?

Our body’s solution is to incorporate the fat and cholesterol into particles called lipoproteins. Lipoprotein particles sequester the fat and cholesterol in their interior and surround them with water soluble phospholipids and proteins. Lipoproteins allow our bodies to transport fat and cholesterol through our bloodstream to the tissues that need them.

The next question, of course, is how the lipoproteins know which cells need the fat and cholesterol. This is where apoproteins like apoE come into play. We can think of the apoE protein as a zip code that directs lipoproteins to cells with an apoE receptor.

Our nervous system contains lots of apoE receptors, and binding of the apoE protein to its receptor is instrumental in the delivery of DHA, EPA, and cholesterol to our nervous system.

DHA and cholesterol are both important for brain health. That is because they are major components of the myelin sheath that wraps around our neurons and protects them. EPA may also be important for brain health because its anti-inflammatory effects are thought to prevent the accumulation of the amyloid plaques that are the hallmark of late-onset Alzheimer’s Disease.

There are three major versions of the APOE gene, APOE2, APOE3, and APOE4. Each of them plays slightly different roles in our body. However, it is the APOE4 version that is of interest to us. About 25% of us have the APOE4 version of the APOE gene and it increases our risk of developing Alzheimer’s Disease by a factor of two.

We do not know why this is, but one hypothesis is that lipoproteins with the apoE4 protein have more difficultly delivering much needed DHA, EPA, and cholesterol to the brain. This is one of the hypotheses that the authors set out to study.

How Was The Study Done?

There are two things you should know about this study.

This was a pilot study designed to test the author’s hypotheses and allow them to choose the correct dose of DHA to use for a subsequent study designed to test whether high-dose DHA can reduce the risk of developing Alzheimer’s Disease.

This was a very small study. That’s because the only way to determine how much DHA and EPA reaches the nervous tissue is to perform a lumbar puncture and obtain cerebrospinal fluid at baseline and again at the end of the study. Lumbar punctures are both painful and a bit risky. They were lucky to find 26 individuals who consented to the lumbar punctures.

This was a double-blind, placebo controlled clinical study.

Half the subjects were given 2,152 mg/day of DHA for 6 months, and half were given a daily placebo consisting of corn and soybean oil for 6 months.

Because previous studies have suggested that B vitamins were important for DHA and EPA uptake by nervous tissue, all subjects received a B vitamin supplement.

Levels of DHA and EPA were measured in both plasma and cerebrospinal fluid at baseline and again at the end of 6 months. Note: The subjects were only supplemented with DHA. The investigators were relying on the body’s ability to convert DHA into EPA.

All subjects were screened for APOE4

Other important characteristics of the study subjects were:

Average age was 69. They were 80% female.

All of them had a close family member who had previously been diagnosed with dementia, but none of them had been diagnosed with cognitive impairment at the time of entry into the study.

Around 45% of them had the APOE4 version of the APOE.

In other words, none of them currently had dementia, but most were at high risk of developing dementia.

How Much DHA Is Needed To Prevent Alzheimer’s?

After 6 months of supplementing with over 2,000 mg/day of DHA:

DHA levels in the blood had increased by 200%.

However, DHA levels in cerebrospinal fluid had increased by only 28%.

Moreover, DHA levels in cerebrospinal fluid were 40% lower in subjects who had the APOE4 gene compared to subjects with the APOE2 and APOE3

EPA levels in cerebrospinal fluid averaged about 15-fold lower than DHA levels. When they looked at the effect of DHA supplementation on EPA levels.

EPA levels in plasma had increased by 50%.

EPA levels in cerebrospinal fluid had increased by 43%.

EPA levels in cerebrospinal fluid were 3-fold lower in subjects who had the APOE4 gene compared to subjects with the APOE2 and APOE3

The authors concluded:

“We observed only a modest (28%) increase in cerebrospinal fluid DHA levels with 2152 mg per day of DHA supplementation. This finding has implications for past clinical trials that have used lower doses (e.g. 1 g daily of DHA supplements or less) and were overwhelmingly negative. Using lower doses of omega-3 supplements may have resulted in limited omega-3 brain delivery.”

“Another aspect affecting the response to DHA supplementation is APOE4 status. Subjects with the APOE4 gene showed lower DHA levels and significantly lower EPA levels than subjects with other APOE genes”.

“In summary, our study suggests that higher doses of omega-3 fatty acids (2 or more g of DHA) are needed to ensure adequate brain delivery, particularly in APOE4 carriers…Past low dose (1 g per day or less) omega-3 supplementation trials in dementia prevention may not have provided adequate brain levels to fully evaluate the efficacy of omega-3 supplementation on cognitive outcomes.”

Based on the results from this study the authors are currently testing the effect of B vitamins and high dose DHA supplementation on cerebrospinal fluid fatty acid levels, brain imaging, and cognitive outcomes in a larger ongoing clinical trial.

What Does This Study Mean For You?

The ability of the omega-3 fatty acids DHA and EPA to reduce the risk of cognitive decline, dementia, and Alzheimer’s Disease is confusing. Studies disagree.

In situations like this, most experts dismiss the hypothesis as “unproven”. However, I like to ask, “What are we missing?”

One recent study provided a clue. It suggested that omega-3s and B vitamins were interdependent. We need both to reduce cognitive decline. However, that might not be the complete answer.

This study gave both DHA and B vitamins to subjects and discovered another interesting clue. The study suggests we may not have been giving subjects enough omega-3s to see a significant effect on cognitive decline.

Let me start by saying this study did not test whether or not DHA supplementation prevents cognitive decline, dementia, and Alzheimer’s Disease. Nor does it tell us how much DHA is needed to prevent Alzheimer’s Disease, other than to show that anything less than 2 g per day is likely to be inadequate.

However, the study did make two important advances:

#1: It showed just how difficult it is to deliver adequate amounts of DHA and EPA to the brain. This is important because it shows:

Most previous studies have not used high enough doses of DHA or DHA plus EPA to evaluate the effect of omega-3 fatty acids on cognitive decline. Those studies were not simply negative. They were doomed to failure. The studies were worthless.

That means we should stop saying that the ability of omega-3s to prevent cognitive decline and diseases like Alzheimer’s is unproven. Instead, we should say that hypothesis has not adequately been tested.

That also means future studies of the ability of DHA to reduce the risk of cognitive decline, dementia, and/or Alzheimer’s will need to use much higher doses or a better delivery system to get adequate amounts of DHA and EPA into the brain.

#2: It showed that the APOE4 gene significantly decreases the ability of the brain to accumulate DHA and EPA. This has several important implications.

Because both DHA and EPA are vital for brain health, this may explain why the APOE4 gene increases the risk of Alzheimer’s Disease.

It also means those at highest risk for Alzheimer’s Disease are the ones who are most likely to have difficulties accumulating DHA and EPA in their brain.

Once again, it means future studies of the ability of supplemental DHA to reduce the risk of Alzheimer’s Disease will need to use much higher doses of DHA.

The Bottom Line

The ability of the omega-3 fatty acids DHA and EPA to reduce the risk of cognitive decline, dementia, and Alzheimer’s Disease is controversial.

Association studies show that greater intake and higher blood levels of the omega-3 fatty acids EPA and DHA are associated with lower risk of Alzheimer’s Disease.

However, most placebo-controlled clinical trials with either DHA alone or DHA + EPA have come up negative.

In situations like this, most experts dismiss the hypothesis as “unproven”. However, I like to ask, “What are we missing?”

One recent study provided a clue. It suggested that omega-3s and B vitamins were interdependent. We need optimal amounts of both to reduce dementia. However, that might not be the complete answer.

This study gave both DHA and B vitamins to participants and discovered another interesting clue. The study suggests we may not have been giving subjects enough omega-3s to see a significant effect on cognitive decline.

The authors of the study hypothesized:

Uptake of DHA and EPA by the brain is very inefficient, and previous studies have not used sufficient doses of DHA or DHA plus EPA to see a significant effect on cognitive impairment.

The APOE4 gene, which is known to increase the risk of Alzheimer’s Disease, further decreases the uptake of DHA and EPA by the brain.

Their study confirmed their hypotheses and made two important advancements:

#1: It showed just how difficult it is to deliver adequate amounts of DHA and EPA to the brain. This is important because it shows:

Most previous studies have not used high enough doses of DHA or DHA plus EPA to evaluate the effect of omega-3 fatty acids on cognitive decline. Those studies were not simply negative. They were doomed to failure. The studies were worthless.

That means we should stop saying that the ability of omega-3s to prevent cognitive decline and diseases like Alzheimer’s is unproven. Instead, we should say that hypothesis has not adequately been tested.

That also means future studies of the ability of DHA to reduce the risk of cognitive decline, dementia, and/or Alzheimer’s will need to use much higher doses or a better delivery system to get adequate amounts of DHA and EPA into the brain.

#2: It showed that the APOE4 gene significantly decreases the ability of the brain to accumulate DHA and EPA. This has several important implications.

Because both DHA and EPA are vital for brain health, this may explain why the APOE4 gene increases the risk of Alzheimer’s Disease.

It also means those at highest risk for Alzheimer’s Disease are the ones who are most likely to have difficulties accumulating DHA and EPA in their brain.

Once again, it means future studies of the ability of supplemental DHA to reduce the risk of Alzheimer’s Disease will need to use much higher doses of DHA.

Based on the results from this study the authors are currently testing the effect of B vitamins and high dose DHA supplementation on DHA and EPA levels in the brain, brain imaging, and cognitive outcomes in a larger ongoing clinical trial.

For more details, read the article above. For a better understanding of the roles of DHA, EPA, and the APOE gene in brain health, you may want to read my “Biochemistry 101” section 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.

Are Saturated Fats Good For You?

April 1, 2014 by Dr. Steve Chaney

Is Everything We Thought We Knew About Fats Wrong?

Author: Dr. Stephen Chaney

Bring out the fatted calf! Headlines are proclaiming that saturated fats don’t increase your risk of heart disease – and that they may actually be good for you.

The study (Annals of Internal Medicine, 160: 398-406, 2014) that attracted all the attention in the press was what we scientists call a meta-analysis. Basically, that is a study that combines the data from many clinical trials to improve the statistical power of the effect being studied.

And it was a very large study. It included 81 clinical trials that looked at the effects of various types of fat on heart disease risk.

Are Saturated Fats Good For You?

The answer to this question is a simple No. The headlines suggesting that saturated fats might be good for you were clearly misleading. The study concluded that saturated fats might not increase the risk of heart disease, but it never said that saturated fats were good for you.

In short, the study concluded that:

Saturated fats, monounsaturated fats and long-chain omega-6 polyunsaturated fats did not affect heart disease risk.

Long chain omega-3 polyunsaturated fats decreased heart disease risk [Note: The original version of the paper said that the decrease was non-significant, which is what the headlines have reported. However, after several experts pointed out an error in their analysis of the omega-3 data, the authors corrected their analysis, and the corrected data show that the decrease in risk is significant.]

Trans fats increased heart disease risk

If those conclusions are correct, they would represent a major paradigm shift. We have been told for years that we should limit saturated fats and replace them with unsaturated fats. Has that advice been wrong?

Is Everything We Thought We Knew About Fats Wrong?

Before we bring out the fatted calf and start heaping butter on our12 ounce steaks, perhaps we should look at some of the limitations of this study.

We Eat Foods, Not Fats

When the authors broke the data down into the effects of individual saturated and unsaturated fatty acids on heart disease risk some interesting insights emerge.

For example, with respect to saturated fats:

Both palmitic acid and stearic acid – which are abundant in palm oil and animal fats – increased the risk of heart disease.

On the other hand, margic acid – which is more abundant in dairy products – decreased the risk of heart disease.

So while the net effect of saturated fats on heart disease risk may be zero, these data suggest:

It is still a good idea to avoid fatty meats, especially red meats, if you want to reduce your risk of heart disease. When you focus on foods, rather than fats this fundamental advice has not changed in over 40 years! In next week’s “Health Tips From the Professor” I will share some of the latest research on the dangers of red meat.

With fatty dairy foods the situation is a little more uncertain. I’m not ready to tell you to break out the butter and whipped cream just yet, but recent research does suggest that dairy foods have some beneficial effects that may outweigh their saturated fat content.

With respect to omega-3 fatty acids:

alpha-linolenic acid – which is found in vegetable oils and nuts and is the most abundant omega-3 fatty acids in our diets – had no effect on heart disease risk.

On the other hand, EPA and DHA – which are found primarily in oily fish and omega-3 supplements – decreased heart disease risk by 20-25%.

Once again, while the net effect of omega-3 fatty acids on heart disease risk was very small, that’s primarily because most Americans consume mostly alpha-linolenic acid and very little EPA and DHA. This study shows that fish oil significantly reduces heart disease risk, which is fully consistent with the heart healthy advice of the American Heart Association and National Institutes of Health over the past decade or more.

What We Replace the Fats With Is Important

A major weakness of the current study is that it did not ask what the individual clinical trials were replacing the fatty acids with. Many of them were simply replacing the saturated fats with carbohydrates. To understand why that is important, you have to go back to the research of Dr. Ancel Keys.

The whole concept of saturated fats increasing the risk of heart disease is based on the groundbreaking research of Dr. Ancel Keys in the 50’s and 60’s. But, it is important to understand what his research showed and didn’t show.

His research showed that when you replaced saturated fats with monounsaturated fats and/or polyunsaturated fats the risk of heart disease was significantly reduced. He was the very first advocate of what we now call the Mediterranean diet. (He lived to 101 and his wife lived to 97, so he must have been on to something.)

Unfortunately, his diet advice got corrupted. The mantra became low fat diets, where the saturated fat was replaced with carbohydrates – mostly simple sugars and refined flours. Since diets containing a lot of simple sugars and refined flours also increase the risk of heart disease you completely offset the benefits of getting rid of the saturated fats.

Just in case you think that is outdated dietary advice, Dr. Key’s recommendations were confirmed by a major meta-analysis published in 2009 (American Journal of Clinical Nutrition, 89: 1425-1432, 2009). That study showed once again that replacing saturated fats with carbohydrates had no effect on heart disease risk, while replacing them with polyunsaturated fats significantly reduced risk.

The Bottom Line:

You can put the fatted calf back out to pasture. The headlines telling you that saturated fats don’t increase the risk of heart disease were overstated and misleading. This study does not represent a paradigm shift. In fact, when you analyze the study in depth it simply reaffirms much of the current dietary advice about fats.

1) When you simply replace saturated fats with carbohydrates, as did many of the studies in the meta-analysis that generated all of the headlines, there is little or no effect on heart disease risk. However, other studies have shown that when you replace the saturated fats with monounsaturated and polyunsaturated fats you significantly reduce heart disease risk.

In short, if you are interested in reducing your risk of heart disease, low fat diets may be of relatively little value while Mediterranean diets may be beneficial. No paradigm shift there. That sounds pretty familiar.

2) Fatty meats, especially red meats, appear to increase the risk of heart disease. No surprises there.

3) Alpha-linolenic acid, the short chain omega-3 fatty acid found in nuts, seeds and vegetable oils, does not decrease heart disease risk. However, EPA and DHA, the long chain omega-3 fatty acids found in fatty fish and fish oil supplements significantly decrease heart disease risk. That’s probably because the efficiency of conversion of alpha-linolenic acid to EPA & DHA in our bodies is only around 10%. No surprises there.

4) The study did suggest that dairy foods may decrease heart disease risk. While there are a few other studies supporting that idea, I’m not ready to break out the butter and whipped cream yet. More research is needed.

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.