Omega-3 Supplements Are Safe

August 27, 2024 by Dr. Steve Chaney

Why Do Clinical Studies Disagree?

Author: Dr. Stephen Chaney

Six weeks ago, the title of my “Health Tips From the Professor” article was, “Are Omega-3 Supplements Safe?” That’s because I was reviewing a study that claimed long-term use of omega-3 supplements increased the risk of atrial fibrillation and stroke. And it had led to headlines like, “Omega-3 Supplements May Increase the Risk of Heart Disease” and “Fish Oil Supplements May Increase The Risk of Stroke and Heart Conditions”.

This week, the title of my article is, “Omega-3 Supplements Are Safe”. I did not choose this title to express my opinion, although I am in general agreement with the statement. I chose that title because the omega-3 pendulum has swung again. The article (M Javaid et al, Journal of The American Heart Association, Volume 13, Number 10: e032390, 2024) I am reviewing today came to the conclusion that omega-3 supplements don’t increase the risk of stroke.

I understand your confusion. You are wondering how scientists can tell you one thing today and the total opposite tomorrow. It is conflicting results like this that cause the public to lose faith in science. And when people lose faith in science they are easily influenced by “snake oil” charlatans on the internet.

So, after I describe this study, I will discuss why scientific studies come up with conflicting results and compare these two studies in detail. That is probably the most important part of this article.

How Was This Study Done?

Scientists from Freeman Hospital and Newcastle University in the UK conducted a meta-analysis combining the data from 120,643 patients enrolled in 11 clinical trials that evaluated the effects of omega-3 supplementation. The inclusion criteria for this meta-analysis were as follows:

The studies were randomized trials that compared omega-3 supplements with placebo or standard treatment. Half the patients received the omega-3 supplement.

The patients were either previously diagnosed with heart disease or were at high risk of developing heart disease.

The studies reported the incidence of bleeding events.

The study asked whether omega-3 supplementation increased the risk of bleeding events (defined as hemorrhagic stroke, intracranial bleeding, or gastrointestinal bleeding) compared to a placebo or standard treatment.

Omega-3 Supplements Are Safe

The results were reassuring for omega-3 supplement users. When compared to a placebo or standard treatment, omega-3 supplements.

Did not increase the risk of overall bleeding events.

Did not increase the risk of hemorrhagic stroke, intracranial bleeding, or gastrointestinal bleeding.

Did not increase the risk of bleeding in patients who were also taking blood thinners (Blood thinners reduce the ability of blood to clot and can lead to bleeding events. This study found that adding omega-3 supplements to these drugs did not increase bleeding risk.

But here is where it gets interesting. One of the 11 studies included in the meta-analysis used a high dose (4 grams/day) of Vascepa, a highly purified ethyl ester of EPA produced by the pharmaceutical company Amarin. When the authors analyzed the data from this study alone, they found that Vascepa:

Increased the relative risk of bleeding by 50% compared to the control group.

- While this sounds scary, the absolute risk of bleeding was only increased by 0.6% compared to the control group.

- I will explain the difference between relative risk and absolute risk below. But for now, you can think of absolute risk as a much more accurate estimate of your actual risk.

The authors of the meta-analysis speculated that the increased bleeding risk associated with the use of Vascepa could be due to the:

High dose of EPA (4 gm/day) or…

Lack of DHA and other naturally occurring omega-3s in the formulation. The authors said:

- The effect of DHA on the endothelial lining is weaker than that of EPA (EPA makes the endothelial lining “less sticky” which reduces its ability to trigger blood clot formation. This is one of the mechanisms by which EPA is thought to decrease blood clot formation.)

- The ability of DHA to inhibit oxidation of Apo-B-containing particles was less sustained than that of EPA (Oxidized Apo-B-containing particles increase the risk of blood clot formation. Inhibition of that oxidation by EPA is another of the mechanisms by which EPA is thought to decrease blood clot formation.)

The authors concluded, “Omega-3 PUFAs [polyunsaturated fatty acids] were not associated with increased bleeding risk. Patients receiving high-dose purified EPA [Vascepa] may incur additional bleeding risk, although its clinical significance is very modest.”

What Is The Difference Between Relative And Absolute Risk?

Relative risk is best defined as the percentage increase or decrease in risk compared to the risk found in a control group. Absolute risk, on the other hand, is the actual increase or decrease in risk in the group receiving the intervention.

Relative risk is an excellent tool for identifying risks. However, it magnifies the extent of the risk, so it can be misleading. For example,

If the absolute risk of some event occurring in the general population was 40%, a 50% increase in relative risk would increase the absolute risk by 20% (40% X 0.5 = 20%) to give a total risk of 60% (40% + 20%). In this case, both the relative and absolute risk are significantly large numbers.

However, if the absolute risk in the general population was 1%, a 50% increase in relative risk would only increase the absolute risk to 1.5%, a 0.5% increase in absolute risk. In this case, the increase in relative risk appears significant, but it is misleading because the absolute increase in risk is a modest 0.5%.

The latter resembles the situation in this study when the authors compared bleeding events in patients receiving Vascepa to those receiving a placebo. The absolute risk of bleeding events in the control group was 1.2%. The risk of bleeding events in the Vascepa group was 1.8%. That is a 50% increase in relative risk but only a 0.6% increase in absolute risk.

Why Do Clinical Studies Disagree?

As I have said many times before, there is no perfect clinical study. Every study has its strengths and its flaws. So, it is perhaps instructive to compare this study and the previous study I reviewed 6 weeks ago. Here are some of the questions I ask when evaluating the strengths and weaknesses of clinical studies.

#1: What kind of study is it?

The previous study was an association study. It can only report on associations. It cannot determine cause and effect. Outcomes like atrial fibrillation and strokes could have been caused by unrelated variables in the population studied.

The current study was a meta-analysis of 11 randomized controlled clinical trials. Because the only difference between the two groups is that one received omega-3 supplements, it can determine cause and effect.

#2: How many people were in the study?

Both studies were very large, so this was not a factor.

#3: How long was the study?

The previous study lasted 12 years. The clinical trials within this meta-analysis lasted one to five years. This is a slight advantage for the previous study because it might be better able to detect risks of chronic use of omega-3 supplements.

#4: How were participants selected?

Participants in the previous study had no previous diagnosis of heart disease while participants in the current study either had a previous diagnosis of heart disease or were at high risk of developing heart disease.

This difference would be relevant if both studies were looking at the benefits of omega-3 supplements. However, the current study was only looking at the side effects of omega-3 supplements, so this is not an important consideration.

#5: How was omega-3 intake monitored?

This was a significant flaw of the previous study. Use of omega-3 supplements was determined by a questionnaire administered when the subjects entered the study. No effort was made to determine whether the amount of omega-3s consumed remained constant during the 12-year study.

The clinical studies within the current meta-analysis were comparing intake of omega-3 supplements to placebo and monitored the use of the omega-3 supplements throughout the study.

#6: What is the dose-response?

This was another serious flaw of the previous study. There was no dose-response data.

The current study provided limited dose-response data. From the data they presented it appeared that the risk of bleeding events was only slightly dose-dependent except for the clinical study with the high dose (4 gm/day) EPA-only Vascepa drug. It was a clear outlier, which is why they analyzed the data from that study independently from the other studies.

#7: What outcomes were measured?

The only common outcome measured in the two studies was hemorrhagic stroke.

The previous study reported that omega-3 supplementation increased the risk of stroke by 5% in the general population. However:

- That result just barely reached statistical significance.

- It was a 5% increase in relative risk. The authors did not report absolute risk.

- It was an association study, so it could not determine cause and effect.

The current study found omega-3 supplementation had no effect on the risk of stroke in a population that either had heart disease or were at high risk of heart disease.

- The exception, of course, was the group taking the high dose Vascepa drug (see below).

#8: Was the risk clinically significant?

As I said above, the previous study only reported relative risk, which can be misleading. However, absolute risk can be calculated from their data. For example,

- The risk of developing atrial fibrillation in the group taking omega-3 supplements was 4.4% (calculated from Table 2 of the manuscript). The authors said that represented a 13% increase in relative risk compared to the group not taking omega-3 supplements. This means the absolute (actual) increase in risk is about 0.6%.

- The risk of stroke in the group taking omega-3 supplements was 1.5% (calculated from Table 2 of the manuscript). The authors said that represented a 5% increase in relative risk compared to the group not taking omega-3 supplements. This means the absolute (actual) increase in risk is about 0.08%.

In the current study the increased risk of stroke in the group taking the high-dose (4 gm/day) EPA-only Vascepa drug was 50% for relative risk, but only 0.6% for absolute risk.

- The authors of the current study argued that, based on absolute risk, the risk of stroke for people taking Vascepa was “clinically insignificant”. I would argue the same is true for the results reported in the previous study and the headlines they generated.

#9: Who sponsored the study?

The previous study was supported by the Bill and Melinda Gates Foundation, an organization that has no obvious interest in the outcome of the study.

The current study is sponsored by Amarin, the pharmaceutical company that manufactures and markets Vascepa.

- However, to their credit, the authors made no effort to hide the negative data about Vascepa.

- - In fact, they highlighted the negative data, noted that the increased bleeding risk with Vascepa was different from the omega-3 supplements studied, and offered possible explanations for why a high potency, EPA-only supplement might increase the risk of bleeding more than a lower potency omega-3 supplement containing both EPA and DHA.

- They did, however, choose to emphasize the 0.6% absolute increase in bleeding risk rather than the 50% relative increase in bleeding risk. However, as I noted above absolute risk is a more accurate way to report risk, especially when the risk in the control group is only 1.2%.

Perspective On This Comparison:

You may be tempted to conclude that the previous study was garbage. Before you do, let me provide some perspective.

The data for that study came from the UK Biobank, which is a long-term collection of data by the British government from over 500,000 residents in the United Kingdom. The data are made available to any researcher who wants to study links between genetic and environmental exposure to the development of disease. However, the data were not collected with any particular study in mind.

This is why omega-3 intake was only determined at the beginning of the study and there was no dose-response information included. The experimental design would have been different if the study were specifically designed to measure the influence of omega-3 supplementation on health outcomes. However, because of cost, the sample size would have been much smaller, which would have made it difficult to show any statistically significant results.

Relative risk rather than absolute risk is almost universally used to describe the results of clinical studies because it is a larger number and draws more attention. However, as I described above, relative risk can be misleading. In my opinion, both relative and absolute risk should be listed in every publication.

What Does This Study Mean For You?

Scientists know that every study has their flaws, so we don’t base our recommendations on one or two studies. Instead, we look at the totality of data before making recommendations. When looking at the totality of data two things stand out.

The bleeding risk with Vascepa is not unique. There are some studies suggesting that high dose (3-4 gm/day) omega-3 supplements containing both EPA and DHA may increase bleeding risk, although probably not to the same extent as Vascepa.

An optimal Omega-3 Index of 8% is associated with a decreased risk of heart disease and does not appear to increase the risk of atrial fibrillation or bleeding events such as hemorrhagic stroke. And for most people, an 8% Omega-3 Index can be achieved with only 1-2 gm/day of omega-3s.

So, my recommendations are the same as they were 6 weeks ago.

Be aware that high-dose (3-4 gm/day) of omega-3 supplements may cause an increased risk of atrial fibrillation and stroke, but the risk is extremely small.

Omega-3 supplementation in the 1-2 gm/day range appears to be both safe and effective.

I recommend getting your Omega-3 Index determined, and if it is low, increasing your omega-3 intake to get it into the 8% range.

The Bottom Line

A recent meta-analysis concluded that omega-3 supplementation does not increase the risk of bleeding events, including hemorrhagic stroke, intracranial bleeding, and gastrointestinal bleeding.

The exception was the high-dose (4 gm/day), EPA-only drug Vascepa, which increases bleeding risk from 1.2% to 1.8%, a 0.6% increase in absolute risk.

This study contradicts a previous study I shared with you only six weeks ago, so I made a detailed comparison of the strengths and weaknesses of each study.

For more details on these studies and what they mean for you, read the article above.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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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 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.

How Much Omega-3s Are Best For Blood Pressure?

April 2, 2024 by Dr. Steve Chaney

What Does This Study Mean For You?

Author: Dr. Stephen Chaney

I am continuing my series on recent omega-3 breakthroughs. Today I am going to cover a recent systematic review and meta-analysis (X Zhang et al, Journal of the American Heart Association, 11: e025071, 2022) that analyzed 71 double blind, placebo-controlled clinical studies with 4,973 subjects to determine the optimal dose of omega-3s needed to lower blood pressure.

But first, I will cover why this study is so important.

High blood pressure is called a “silent killer”. For most of us our blood pressure creeps up year after year, decade after decade. Factors like inactivity, obesity, smoking, poor diet, and excess alcohol consumption speed the increase.

Unfortunately, the symptoms of high blood pressure – things like headaches, anxiety, fatigue, and blurred vision – are easy to ignore or confuse with other health problems. And if these symptoms are ignored long enough, the result can be sudden death due to a stroke or heart attack.

Alternately, the consequence could be things like congestive heart failure, kidney failure, vision loss, and memory loss that change your quality of life forever. And once the genie is out of the bottle, it can never be put back again. The damage is permanent.

Omega-3s are often recommended for keeping blood pressure in the normal range. In fact, in 2019 the FDA approved a qualified health claim stating, “Consuming eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 fatty acids in food or dietary supplements may reduce the risk of hypertension (high blood pressure) and coronary heart disease.”

But the amount of omega-3s needed to reduce the risk of high blood pressure is uncertain. Previous studies have come up with conflicting results. That is the question the study I will discuss today was designed to answer.

How Was This Study Done?

The investigators included 71 studies published between 1987 and 2020 with a total of 4,793 subjects ranging in age from 22 to 86 years in their systematic review and meta-analysis. The studies were all randomized, placebo-controlled trials looking at the effectiveness of omega-3 intake (primarily in the form of food or supplements containing both EPA and DHA) at lowering blood pressure. The placebo used in these studies was olive oil or other vegetable oils.

The studies included in this meta-analysis:

Included omega-3 intake from both diet (mackerel, salmon, trout, or tuna) and supplements (fish oil, algal oil, or purified omega-3 ethyl esters).

Were conducted in populations from Europe, North America, Australia and other Pacific islands, and Asia.

Included subjects with normal blood pressure as well as those with high blood pressure.

Ranged in length from 5 to 52 weeks (the average was 10 weeks).

Included approximately equal numbers of men and women.

The meta-analysis excluded studies that:

Lacked a placebo.

Lasted less than 4 weeks.

Included blood pressure medications.

Included individuals with preexisting cardiovascular events.

The data from these trials was analyzed by a statistical method called a 1-stage cubic spline regression model. This is a recently developed statistical method which the investigators stated was superior to the statistical methods used in previous studies because it reduces the likelihood the results are influenced by investigator bias.

How Much Omega-3s Are Best For Blood Pressure?

When the investigators combined the data from all 71 studies:

The maximum reduction in both systolic and diastolic blood pressure was observed between 2g/d and 3 g/d.

The dose response was non-linear. Doses above 3 g/d offered no additional benefit.

When the investigators looked at subgroups within the studies:

Reduction in blood pressure was seen in both subjects with normal blood pressure and those with high blood pressure.

- However, reduction in blood pressure and the dose response were different in the two groups.

- - In subjects with normal blood pressure the dose response was non-linear with the optimum reduction between 2 and 3 g/d.

- - In subjects with high blood pressure the reduction in blood pressure was greater and the dose response was linear. The authors recommended a dose ≤ 3 g/d EPA + DHA for people with high blood pressure.

Subjects with hyperlipidemia had a greater reduction in blood pressure than subjects with normal lipid levels, and the dose-response was linear.

Subjects over the age of 45 had a greater reduction in blood pressure than subjects under the age of 45, and the dose response was linear.

There were no significant differences between:

- Diet versus supplementation.

- Type of omega-3 supplement (natural fish oil versus purified ethyl ester).

- Sex.

The authors concluded, “This dose-response meta-analysis demonstrates that the optimal combined intake of omega-3 fatty acids for blood pressure lowering is likely between 2 g/d and 3 g/d. Doses of omega-3 fatty acid intake above the recommended 3 g/d may be associated with additional benefits in lowering blood pressure among groups at high risk of cardiovascular disease.”

I should probably explain the reasoning behind this conclusion.

79% of the studies included in this meta-analysis were performed with subjects who had normal blood pressure. This group had a non-linear reduction in blood pressure with an optimal reduction between 2 and 3 g/d EPA + DHA.

- Because of its size this group exerted a major influence on the results, which explains why the average results for the entire group showed a non-linear reduction in blood pressure with an optimal reduction between 2 and 3 g/d EPA + DHA.

- Subjects with normal blood pressure and normal lipid levels are at low risk of cardiovascular disease. The high-risk groups (high blood pressure, high cholesterol and/or triglyceride levels, and over 45) all had a linear dose response suggesting that doses above 3 g/d EPA + DHA may be optimal.

The authors also said, “We found associations [between omega-3 intake and blood pressure] among both hypertensive (high blood pressure) and nonhypertensive (normal blood pressure) groups, suggesting that omega-3 fatty acids could be beneficial for controlling blood pressure even before the onset of hypertension.

This means that the intake of omega3 fatty acids could have implications on a person’s future risk of stroke, ischemic heart disease, and all-cause mortality.”

In other words, they are saying their data suggests that EPA + DHA intakes in the 2-3 g/d range may prevent high blood pressure and the effects it can have on our health.

What Does This Study Mean For You?

The authors of this study claim their data support a dose of 2-3 mg/d of EPA + DHA to prevent a future increase in blood pressure and all its associated health consequences. They also say that an EPA+ DHA dose ≥ 3g/d may be optimal for people who already have high blood pressure and/or other risk factors for heart disease.

I am not an expert on statistics, so I cannot evaluate the author’s claim that their statistical method was superior to the methods used in earlier studies that gave conflicting results.

However, their results are consistent with recommendations of several major health and government agencies.

For example, the European Food Safety Authority has said, “An intake of EPA and DHA of ~3 g/d is required to bring out the claimed hypotensive (blood pressure lowering) effect”.

The FDA has approved qualified health claims stating that consuming EPA and DHA in foods or dietary supplements may reduce the risk of hypertension (high blood pressure) and coronary heart disease but did not recommend a dose to achieve these results.

The American Heart Association has recommended ~ 1 g/d of EPA + DHA for patients with documented coronary heart disease and 2–4 g/day of EPA + DHA to lower triglycerides.

And the American Heart Association features this article on their website with the headline, “Consuming about 3 grams of omega-3 fatty acids a day may lower blood pressure.”

When we contrast that with the fact that the average American gets less than 100 mg/d of EPA + DHA from their diet it is obvious that many Americans would likely benefit from increasing the amount of EPA and DHA in their diet.

The Rest Of The Story

There are four additional points I would like to make:

In trying to explain the differences between dose response in high and low risk subjects, the authors said, “There could be mechanistic differences in bioavailability and efficacy of omega-3 fatty acid intake in these populations.”

In last week’s “Health Tips From the Professor” article I reviewed a study that measured individual differences in the utilization of EPA and DHA and concluded that a blood measurement called Omega-3 Index was a more reliable indicator of health outcomes than the dose of omega-3s consumed.

For that reason, I recommend personalizing your dose of EPA + DHA to reach an Omega-3 Index of 8%, which appears to be optimal for heart health and provides significant blood pressure reduction. This is an iterative process which will require frequent measurement of your omega-3 index and adjustment of EPA + DHA dose until you find the level of EPA + DHA supplementation you need to achieve an Omega-3 Index of 8%.

This study and similar studies measure the health benefits of the long chain omega-3 fatty acids EPA and DHA. Short chain omega-3s from nuts, seeds, and plant oils are healthy, but their conversion to EPA and DHA is very inefficient.

Both the FDA and American Heart Association recommend that doses of EPA + DHA above 3 g/d should be taken under a physician’s supervision because high doses can cause bleeding problems.

This is another reason for basing your intake of EPA + DHA on Omega-3 Index rather than on the dose recommended by a clinical study. Based on dozens of clinical studies, an Omega-3 Index of 8% appears to be safe unless you have a bleeding disorder or are on a blood-thinning medication (see below).

If you are on a medication to thin your blood, you should consult with your physician before increasing or decreasing your omega-3 intake because changes in dietary omega-3s can affect the optimal dose of medication they prescribe.

The Bottom Line

A recent study looked at the dose of EPA + DHA needed to lower blood pressure.

The study concluded that a dose of 2-3 mg/d of EPA + DHA was optimal for preventing a future increase in blood pressure and all its associated health consequences.

It also concluded that an EPA+ DHA dose ≥ 3g/d was optimal for lowering blood pressure in people who already have high blood pressure and/or other risk factors for heart disease.

Based on previous studies, I recommend optimizing your omega-3 index rather than relying on a dose of EPA + DHA that may not be right for you.

For more details about this study and what it means to you read the article above.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease.

______________________________________________________________________________

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.

How Much Omega-3s Do Children Need?

September 6, 2022 by Dr. Steve Chaney

What Does This Study Mean For Your Children?

Author: Dr. Stephen Chaney

It is back to school time again. If you have children, you are probably rushing around to make sure they are ready.

Backpack…Check.
Books…Check
School supplies…Check
Omega-3s…???

Every parent wants their child to do their best in school. But do they need omega-3s to do their best? I don’t need to tell you that question is controversial.

Some experts claim that omega-3 supplementation in children improves their cognition. [Note: Cognition is defined as the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses. In layman’s terms that means your child’s ability to learn.]

Other experts point out that studies in this area disagree. Some studies support these claims. Others don’t. Because the studies disagree these experts conclude there is no good evidence to support omega-3 supplementation in children.

The authors of this study (ISM van der Wurff et al, Nutrients, 12: 3115, 2020) took a different approach. They asked why these studies disagreed. They hypothesized that previous studies disagreed because there is a minimal dose of omega-3s needed to achieve cognitive benefits in children. In short, they were asking how much omega-3s do children need.

They based their hypothesis on recent studies showing that a minimum dose of omega-3s is required to show heart health benefits in adults.

What Have We Learned From Studies on Omega-3s And Heart Health?

The breakthrough in omega-3/heart health studies came with the development of something called the omega-3 index. Simply put, omega-3s accumulate in our cell membranes. The omega-3 index is the percent omega-3s in red blood cell membranes and is a good measure of our omega-3 status.

Once investigators began measuring the omega-3 index in their studies and correlating it with heart health, it became clear that:

An omega-3 index of ≤4% correlated with a high risk of heart disease.

An omega-3 index of ≥8% correlated with a low risk of heart disease.

Most Americans have an omega-3 index in the 4-6% range.

Clinical studies in which participants’ omega-3 index started in the low range and increased to ~8% through supplementation generally showed a positive effect of omega-3s on reducing heart disease risk. [I say generally because there are other factors in study design that can obscure the effect of omega-3s.]

This is the model that the authors adopted for their study. They asked how much omega-3s do children need to show a positive effect of omega-3s on their cognition (ability to learn).

How Was The Study Done?

The authors included 21 studies in their analysis that met the following criteria:

All studies were placebo controlled randomized clinical trials.

The participants were 4-25 years old and had not been diagnosed with ADHD.

Supplementation was with the long-chain omega-3s DHA and/or EPA.

The trial assessed the effect of omega-3 supplementation on cognition.

I do not want to underestimate the difficulties the authors faced in their quest. The individual studies differed in:

The dose of omega-3s.

- The relative amount of DHA and EPA.

- Whether omega-3 index was measured. Only some of the studies measured fatty acid levels in the blood. The authors were able to calculate the omega-3 index in these studies.

How cognition (ability to learn) was measured.

The age of the children.

- 20 of the studies were done with children (4-12 years old) or late adolescents (20-25 years old).

- Only one study was done on early to middle adolescents (12-20 years old).

All these variables influence the outcome and could obscure the effect of omega-3s on cognition.

In short, determining the omega-3 dose-response for an effect on cognition was a monumental task. It was like searching for a needle in a haystack. These authors did a remarkable job.

How Much Omega-3s Do Children Need?

Here is what the scientists found when they analyzed the data:

60% of the studies in which an omega-3 index of ≥6% was achieved showed a beneficial effect of omega-3 supplementation on cognition (ability to learn) compared to 20% of the studies that did not achieve an omega-3 index of 6%.

- That is a 3-fold difference in effectiveness once a threshold of 6% omega-3 index was reached.

50% of the studies in which a dose of ≥ 450 mg/day of DHA + EPA was used showed a beneficial effect of omega-3 supplementation on cognition (ability to learn) compared to 25% of the studies that used <450 mg/day DHA + EPA.

- That is a 2-fold difference in effectiveness once a threshold of 450 mg/day DHA + EPA was given.

The authors concluded, “Daily supplementation of ≥450 mg/day DHA and/or EPA and an increase in the omega-3 index to >6% makes it more likely to show efficacy [of omega-3s] on cognition (ability to learn) in children and adolescents.”

What Does This Study Tell Us?

It is important to understand what this study does and does not tell us.

This study does not:

Prove that omega-3 supplementation can improve cognition (ability to learn) in children and adolescents.

Define optimal levels of DHA + EPA.

Tell us whether DHA, EPA, or a mixture is better.

It was not designed to do any of these things. It was designed to give us a roadmap for future studies. It tells us how to design studies that can provide definitive answers to these questions.

This study does:

Define a threshold dose of DHA + EPA for future studies (450 mg/day).

Tells us how to best use the omega-3 index in future studies. To obtain meaningful results:

- Participants should start with an omega-3 index of 4% or less.

- Participants should end with an omega-3 index of 6% or greater.

In my opinion, future studies would also be much more effective if scientists in this area of research could agree on a single set of cognitive measures to be used in all subsequent studies.

In short, this study provides critical information that can be used to design future studies that will be able to provide definitive conclusions about omega-3s and cognition in children.

What Does This Study Mean For Your Children?

As a parent or grandparent, you probably aren’t interested in optimizing the design of future clinical studies. You want answers now.

Blood tests for omega-3 index are available, but they are not widely used. And your insurance may not cover them.

So, for you the most important finding from this study is that 450 mg/day DHA + EPA appears to be the threshold for improving a child’s cognition (their ability to learn).

450 mg/day is not an excessive amount. The NIH defines adequate intakes for omega-3s as follows:

4-8 years: 800 mg/day
9-13 years: 1 gm/day for females, 1.2 gm/day for males
14-18 years: 1.1 gm/day for females and 1.6 gm/day for males.
With at least 10% of that coming from DHA + EPA

Other organizations around the world recommend between 100 mg/day and 500 mg/day DHA + EPA depending on the age and weight of the child and the organization.

Most children need supplementation to reach adequate omega-3 intake. The NIH estimates the average child only gets around 40 mg/day omega-3s from their diet. No matter which recommendation you follow, it is clear that most children are not getting the recommended amount of DHA + EPA in their diet.

Genetics.
Diet.
Environment.
The value placed on learning by parents and peers.

Supplementation is just one factor in your child’s ability to learn. But it is one you can easily control. . And if your child is like most, he or she is probably not getting enough omega-3s in their diet.

The Bottom Line

It is back to school time again. Every parent wants their child to do their best in school. But do they need omega-3s to do their best? I don’t need to tell you that question is controversial.

Some studies support these claims, but others don’t. Because the studies disagree some experts conclude there is no good evidence to support omega-3 supplementation in children.

The authors of a recent study took a different approach. They asked why these studies disagreed. They hypothesized that previous studies disagreed because there was a minimal dose of omega-3s needed to achieve cognitive benefits in children. They asked how much omega-3s children need.

They analyzed the data from 21 previous studies looking at the effect of omega-3 supplementation on cognition (ability to learn) in children and adolescents. Their analysis showed:

60% of the studies in which an omega-3 index of ≥6% was achieved showed a beneficial effect of omega-3 supplementation on cognition (ability to learn) compared to 20% of the studies that did not achieve an omega-3 index of 6%.

- That is a 3-fold difference in effectiveness once a threshold of 6% omega-3 index was reached.

50% of the studies in which a dose of ≥ 450 mg/day of DHA + EPA was used showed a beneficial effect of omega-3 supplementation on cognition (ability to learn) compared to 25% of the studies that used <450 mg/day DHA + EPA.

- That is a 2-fold difference in effectiveness once a threshold dose of 450 mg/day DHA + EPA was given.

The authors concluded, “Daily supplementation of ≥450 mg/day DHA + EPA and an increase in the omega-3 index to >6% makes it more likely to show efficacy [of omega-3s] on cognition (ability to learn) in children and adolescents.”

For more details on the study and what it means for your children and grandchildren, 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.

What Supplements Help Mental Health?

January 14, 2020 by Dr. Steve Chaney

Do Omega-3s Reduce Depression?

Author: Dr. Stephen Chaney

We are in the midst of a mental health crisis. According to the latest statistics:

· 19% of adults in the United States have some form of mental illness.

· 16.5% of youth ages 6-17 have some form of mental illness.

· The 5 most commonly diagnosed forms of mental illness are anxiety, depression, post-traumatic stress disorder, bipolar disease, and ADHD.

Even worse, mental illness appears to be increasing at an alarming rate among young people. For example:

· Between 2005 and 2017 depression increased 52% among adolescents.

· Between 2002 and 2017 depression increased 63% in young adults.

· Between 1999 and 2014 suicides have increased 24% in young adults. In the past few years suicides have been increasing by 2% a year in this group.

Much has been written about the cause of this alarming increase in mental illness. The short answer is that we don’t really know. But the most pressing question is what do we do about it?

The medical profession relies on powerful drugs to treat the symptoms of mental illness. These drugs don’t cure the illness. They simply keep the symptoms under control. Plus, if you have ever listened closely to the advertisements for these drugs on TV, you realize that they all have serious side effects that adversely affect your quality of life.

My “favorite” example is drugs for anxiety and depression. You are told that one of the side effects is “suicidal thoughts”. That means that the very drug someone could be prescribed to prevent suicides might actually increase their risk of suicide. Why would anyone take such a drug?

If drugs are so dangerous, what about supplements? Do they provide a safe, natural alternative for reducing the symptoms of mental illness? Some supplement companies claim their products cure mental illness. Are their claims true or are they just trying to empty your wallet?

How is a consumer to know which of these supplement claims are true and which are bogus? Fortunately, an international team of scientists has scoured the literature to find out which supplements have been proven to reduce mental health symptoms.

How Was The Study Done?

This was a massive study (J. Firth et al, World Psychiatry, 18: 308-324, 2019. It was a meta-review of 33 meta-analyses of randomized, placebo-controlled trials with a total of 10,951 subjects. The clinical trials included in this analysis analyzed the effect of 12 nutrients, either alone or in combination with standard drug treatment, on symptoms associated with 10 common mental disorders.

To help you understand the power of this meta-review, let me start by defining the term “meta-analysis”. A meta-analysis combines the data from multiple clinical studies to increase the statistical power of the data. Meta-analyses are considered to be the gold standard of evidence-based evidence.

However, not all meta-analyses are equally strong. They suffer from the “Garbage-In, Garbage-Out” phenomenon. Simply put, they are only as strong as the weakest clinical studies included in their analysis.

That is the strength of this meta-review. It did not simply combine the data from all 33 meta-analyses. It used stringent criteria to evaluate the quality of each meta-analysis and weighted the data appropriately.

What Supplements Help Mental Health?

The strongest evidence was for omega-3 supplements. In the worlds of the authors:

· “Across 13 independent randomized control clinical trials in 1,233 people with major depression, omega-3 supplements reduced depressive symptoms significantly.”

o The average dose of omega-3s in these studies was 1,422 mg/day of EPA.

o The effect was strongest for omega-3 supplements containing more EPA than DHA and for studies lasting longer than 12 weeks.

o There was no evidence of publication bias in these studies. This is a very important consideration. Publication bias means that only studies with a positive effect were published while studies showing no effect were withheld from publication. That makes the effect look much more positive than it really is. The fact there was no evidence of publication bias strengthens this conclusion.

o Omega-3 supplements were more effective when used in combination with antidepressant drugs, but there was some evidence of publication bias in those studies.

· “Across 16 randomized control clinical trials reporting on ADHD symptom domains, significant benefits were observed for both hyperactivity/impulsivity and inattention.”

· Omega-3s had no significant effect on schizophrenia or bipolar disorder other than a mild reduction in depressive symptoms.

There was strong, but not definitive, evidence for folic acid and methylfolate supplements for depression.

· When used in conjunction with antidepressants both folic acid and methylfolate supplements “…were associated with significantly greater reductions in depressive symptoms compared to placebo, although there was large heterogeneity between trials.”

· The largest effects were observed with high dose methylfolate. In the words of the authors: “Two randomized control clinical trials examining a high dose (15 mg/day) of methylfolate administered in combination with antidepressants found moderate-to-large benefits for depressive symptoms.” However, to put this into perspective:

o 15 mg/day is 3,750% of the RDA. This is a pharmacological dose and should only be administered under the care of a physician.

o A smaller dose of 7.5 mg/day is ineffective.

o No comparison was made with folic acid at this dose, so we do not know whether folic acid would be equally effective.

· The authors concluded that there is emerging evidence for positive effects of vitamin D (>1,500 IU/day) for major depressive disorders and N-acetylcysteine (2-3 gm/day) in combination with drugs for mood disorders and schizophrenia. The term “emerging evidence” means there have been several recent studies reporting positive results, but more research is needed.

· The authors did not find evidence supporting the use of other vitamin and mineral supplements (E, C, zinc, magnesium, and inositol) for treating mental health disorders.

· The authors did not find enough high-quality studies to support claims about the effects of prebiotics or probiotics on mental health disorders.

Do Omega-3s Reduce Depression?

The evidence supporting the effectiveness of omega-3s in reducing symptoms of depression is strong. In the words of the authors: “The nutritional intervention with the strongest evidentiary support is omega-3, in particular EPA. Multiple meta-analyses have demonstrated that it has significant effects in people with depression, including high-quality meta-analyses with good confidence in findings…”

However, before you throw away your antidepressants and replace them with an omega-3 supplement, let me put this study into perspective for you.

· Depression can be a serious disease. If you just feel a little blue from time to time, try increasing your omega-3 intake. However, if you have major depression, don’t make changes to your treatment plan without consulting your physician.

· The best results were obtained when omega-3s were used in combination with antidepressants. This should be your starting point.

· Ideally, adding omega-3s to your treatment plan will allow your doctor to reduce or eliminate the drugs you are taking. That would have the benefit of reducing side effects associated with the drugs. However, I would like to re-emphasize this is a decision to take in consultation with your doctor. [My only caveat is if your doctor is unwilling to even consider natural approaches like omega-3 supplementation, it might be time to find a new doctor.]

· Finally, omega-3 supplementation is only one aspect of a holistic approach to good mental health. A healthy diet, exercise, supplementation, and stress reduction techniques all work together to keep your mind in tip-top shape.

The Bottom Line

There are lots of supplements on the market promising to cure depression and other serious mental health issues. Are they effective or are the claims bogus? Fortunately, a recent meta-review of 33 meta-analyses of high-quality clinical trials has answered that question. Here is their conclusion:

· The evidence is strongest for omega-3s and depression.

o The average dose of omega-3s in these studies was 1,422 mg/day of EPA.

o The effect was strongest for omega-3 supplements containing more EPA than DHA and for studies lasting longer than 12 weeks.

· There is fairly strong evidence for folate/folic acid supplements and depression, although there was large heterogeneity between trials.

· There is emerging evidence for vitamin D (>1,500 IU/day) and depression and N-acetylcysteine (2-3 gm/day) for depression and schizophrenia.

· Evidence for other supplements is currently inconclusive.

However, before you throw away your antidepressants and replace them with an omega-3 supplement, let me put this study into perspective for you.

· The best results were obtained when omega-3s were used in combination with antidepressants. That should be your starting point.

For more details, read the article above.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

Is Fish Oil Really Snake Oil?

February 11, 2014 by Dr. Steve Chaney

Does Fish Oil Reduce Heart Disease Risk?

Author: Dr. Stephen Chaney

One of my readers recently sent me a video titled “Is Fish Oil Just Snake Oil?” and asked me to comment on it. The doctor who made the video claimed that the most recent studies had definitively shown that omega-3 fatty acids, whether from fish or fish oil, do not decrease the risk of heart attack, stroke or cardiovascular death. He went on to say that the case was closed. There was no point in even doing any more studies.

My reader, like many of you, was confused. Wasn’t it just a few years ago we were being told that clinical studies have shown that omega-3 fatty acids significantly reduce the risk of heart disease? Hadn’t major health organizations recommended omega-3 fatty acids as part of a heart health diet? What has changed?

The answer to the first two questions is a resounding YES, and “What has changed?” is THE story. Let me explain.

Fish Oil And Heart Disease Risk In Healthy People

If we look at intervention studies in healthy people (what we scientists refer to as primary prevention studies) the results have been pretty uniform over the years. In a primary prevention setting, fish oil cannot be shown to significantly reduce the risk of heart disease (Rizos et al, JAMA, 308: 1024-1033, 2012).

That’s not unexpected because it is almost impossible to show that any intervention significantly reduces the risk of heart disease in healthy populations. For example, as I pointed out in recent Health Tips From the Professor (“Do Statins Really Work?” and “Can An Apple A Day Keep Statins Away?”) you can’t even show that statins significantly reduce heart attack risk in healthy populations.

If you can’t prove that statins reduce the risk of heart attacks in a healthy population, it should come as no surprise that you can’t prove that fish oil reduce heart attacks in a healthy population. To answer that question we need to look at whether fish oil reduces the risk of heart attacks in high risk populations.

Fish Oil And Heart Disease Risk In Sick People – The Early Studies

Most of the early studies looking at the effect of fish oil in patients at high risk of cardiovascular disease (what we scientists refer to as secondary prevention studies) reported very positive results.

For example, the DART1 study (Burr et al, Lancet, 2: 757-761, 1989) and the US Physician’s Health Study (Albert et al, JAMA, 279: 23-28, 1998) reported a 29% decrease in total mortality and a 52% decrease in sudden deaths related to heart disease in patients consuming diets rich in omega-3 containing fish.

Even more striking was the GISSI-Prevenzione study (Marchioli et al, Lancet, 354: 447-455, 1999; Marchioli et al, Eur. Heart J, 21: 949-952, 2000; Marchioli et al, Circulation, 105: 1897-1903, 2002). This was a very robust and well designed study. It looked at the effect of a fish oil supplement providing 1 g/day of omega-3 fatty acids on the risk of a second heart attack in 11,323 patients who had survived a non-fatal heart attack within the last 3 months – a very high risk group.

The results were clear cut. Over the next 3.5 years supplementation with fish oil reduced overall death by 15% and sudden death due to heart disease by 30% compared to a placebo. And, if you looked at the first 4 months, when the risk of a second heart attack is highest, the fish oil supplement reduced the risk of overall death by 41% and sudden death by 53%.

The authors estimated that treating 1,000 heart attack patients with 1 g/day of fish oil would save 5.7 lives per year. That is almost identical to the 5.2 lives saved per 1,000 patients per year by the statin drug pravastatin in the LIPID trial (NEJM, 339: 1349-1357, 1998).

No wonder the American Heart Association said that patients “could consider fish oil supplementation for heart disease risk prevention.”

Fish Oil And Heart Disease Risk In Sick People – The Latest Studies

However, the most recent studies have been uniformly negative. For example, the ORIGIN trial (Bosch et al, NEJM, 367: 309-318, 2012) treated 12,536 patients who were considered at high risk of heart disease because of diabetes or pre-diabetes with either 1 g/day of fish oil or a placebo. This was also a robust, well designed study, and it found no effect of the fish oil supplement on either heart attacks or deaths due to heart disease.

Similarly, a recent meta-analysis looking at the combined effects of 14 randomized, double-blind, placebo-controlled trials in patients at high risk of heart disease found no significant effect of fish oil supplements on overall deaths, sudden death due to heart disease, heart attacks, congestive heart failure or stroke (Kwak et al, Arch. Int. Med., 172: 686-694, 2012).

No wonder you are confused by all of the conflicting studies. You must be wondering: “Is the American Heart Association wrong?” “Are fish oil supplements useless for reducing heart disease risk?”

What Has Changed Between The Early Studies & The Latest Studies?

When a trained scientist sees the outcome of well designed clinical studies change over time, he or she asks: “What has changed in the studies?” It turns out that a lot has changed.

1) In the first place the criteria for people considered at risk for heart attack and stoke have changed dramatically. Not only has the definition of high cholesterol” been dramatically lowered, but cardiologists now treat people for heart disease if they have inflammation, elevated triglycerides, elevated blood pressure, diabetes, pre-diabetes or minor arrythmia.

For example, the GISSI-Prevenzione study recruited patients who had a heart attack within the past three months, while the ORIGIN study just looked at people who had diabetes or impaired blood sugar control. While both groups could be considered high risk, the patients in the earlier studies were at much higher risk for an imminent heart attack or stroke – thus making it much easier to detect a beneficial effect of omega-3 supplementation.

2) Secondly, the standard of care for people considered at risk for heart disease has also changed dramatically. In the earlier studies patients were generally treated with one or two drugs – generally a beta-blockers and/or drug to lower blood pressure. In the more recent studies the patients generally receive at least 3 to 5 different medications – medications to lower cholesterol, lower blood pressure, lower triglycerides, reduce inflammation, reduce arrhythmia, reduce blood clotting, and medications to reduce the side effects of those medications.

Since those medications perform many of the beneficial effects of omega-3 fatty acids, it is perhaps no surprise that it is now very difficult to show any additional benefit of omega-3 fatty acids in patients on multiple medications.

The bottom line is that we are no longer asking the same question. The earlier studies were asking whether fish oil supplements reduce the risk of heart attacks or cardiovascular death in patients at high risk of heart disease. The more recent studies are asking whether fish oil supplements provide any additional benefits in a high risk population that is already on 3-5 medications to reduce their risk of heart disease.

However, the people who are writing the headlines you are reading (and the videos you are watching) are not making that distinction. They are pretending that nothing has changed in the way the studies are designed. They are telling you that the latest studies contradict the earlier studies when, in fact, they are measuring two different things.

Is Fish Oil Really Snake Oil?

Was the doctor who made the video “Is Fish Oil Just Snake Oil?” correct in saying that omega-3 fatty acids are ineffective at reducing the risk of heart disease? The answer is yes and no.

If you take the medical viewpoint that the proper way to treat anyone at the slightest risk of heart disease is with 3-5 medications – with all of their side effects, the answer seems to be pretty clear cut that adding fish oil to your regimen provides little additional benefit.

However, that is not the question that interests me. I’d like to know whether I can reduce my risk of heart attack and cardiovascular death by taking omega-3 fatty acids in place of those drugs – as the original studies have shown.

I’m sure many of my readers feel the same way.

The Bottom Line

Studies performed prior to 2000 have generally shown that fish oil supplements reduce the risk of a second heart attack in patients who have previously had a heart attack. One study even suggested that they were as effective as statin drugs at reducing heart attack risk in this population.

Recent studies have called into question the beneficial effects of fish oil supplements at reducing the risk of heart disease. However, these studies were performed with lower risk patients and the patients were on 3-5 medications to reduce their risk of heart attack or stroke.

The recent studies are no longer evaluating whether fish oil supplements can reduce the risk of heart disease. They are asking whether they have any additional beneficial effects for people taking multiple medications. That’s a totally different question.

So ignore the headlines saying that fish oil is snake oil. If you are content taking multiple medications to reduce your risk of heart disease, it is probably correct to say that omega-3 fatty acids provide little additional benefit.

However, if you are interested in a more holistic, drug-free approach to reducing your risk of heart disease, I still recommend omega-3 fatty acids as part of a heart healthy diet, as does the American Heart Association.

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.