Omega-3s and Heart Disease Archives - Health Tips From The Professor

600th Issue Celebration

November 5, 2024 by Dr. Steve Chaney

Nutrition Advances Over The Last Two Years

Author: Dr. Stephen Chaney

In the nearly twelve years that I have been publishing “Health Tips From The Professor”, I have tried to go behind the headlines to provide you with accurate, unbiased health information that you can trust and apply to your everyday life.

The 600^th issue of any publication is a major cause for celebration and reflection – and “Health Tips From The Professor” is no different.

I am dedicating this issue to reviewing some of the major stories I have covered in the past 100 issues. There are lots of topics I could have covered, but I have chosen to focus on three types of articles:

Articles that have debunked long-standing myths about nutrition and health.

Articles that have corrected some of the misinformation that seems to show up on the internet on an almost daily basis.

Articles about the issues that most directly affect your health.

Here are my picks from the last two years:

Weight Loss Diets

Since it is almost January, let’s start with a couple of articles about diet and weight loss (or weight gain). I have covered the effectiveness of the Paleo, Keto, Mediterranean, DASH, vegetarian, and Vegan diets for both short and long-term weight loss in my book “Slaying The Food Myths”, so I won’t repeat that information here. Instead, I will share a few updates from the past 100 issues.

Is Time-Restricted Eating Better Than Other Diets? Time-restricted eating is one of the latest fads. But is it really better than other diets for weight loss and improved health? In this article I reviewed two studies that compare time-restricted eating with diets that do not restrict time of eating but cut calories to the same extent. You may be surprised at the results.

Can You Lose Weight Without Dieting? In this article I share 8 tips for losing weight without going on a diet. The article is based on research by Dr. Brian Wansink, a behavioral psychologist who specializes in studying how external clues influence our eating patterns. As you might suspect his 8 tips for losing weight have nothing to do with counting calories or going on restrictive diets.

Healthy Diets

Is Whole Fat Dairy Healthy? For years dietary guidelines have been telling us to select low fat dairy foods. But some health gurus are telling you that isn’t true. They claim whole fat dairy is healthy. So, you are probably wondering, “What is the scoop (as in ice cream) on whole fat dairy?” In this article I look at the study behind the headlines and answer that question. But the answer is not a simple “Yes” or “No”. The answer is more nuanced. It turns out that whole fat dairy is healthier in some diets than in others.

Are Low Carb Diets Healthy? Are low carb diets good for you or bad for you? It depends on which study you quote. Two major studies in recent years have come to opposite conclusions. In this article I help you sort through the conflicting studies and rephrase the question. Instead of, “Are low carb diets healthy”, the question should be, “Which low carb diets are healthy?”

Are All Plant-Based Diets Healthy? Plant-based diets have acquired a “health halo” in recent years. Your mama told you to eat your fruits and vegetables. And many health gurus have been telling you not to neglect your grains, legumes, nuts, and seeds as well. But some of these foods require a lot of food preparation.

Never fear! The food industry has come to your rescue with a wide variety of processed plant-based foods. No need for food prep. But are they as good for you as the unprocessed plant foods they replace? In this article I review a study that answers that question.

You probably know what that answer is, but the article is worth a read anyway. That is because the study also asks whether vegan and vegetarian diets are healthier than other primarily plant-based diets. And you may not know the answer to that question.

Diet And Heart Disease

Are Eggs Bad For You? For years we were told that eggs are bad for us because they contain cholesterol. Then we were told that eggs in moderation may not increase our risk of heart disease. And recently studies have appeared claiming eggs may be good for our hearts. What is the truth about eggs and heart disease? In this article I review a recent study claiming eggs are bad for our heart and put that study into the context of other recent studies to clear up the “eggfusion”.

Which Diets Are Heart Healthy? Every popular diet claims to help you lose weight, reduce your risk of diabetes, and reduce your risk of heart disease. All these claims can’t be true. Which diets deliver on their promises, and which are just pretenders? In this article I review a recent study that answered that question for heart disease.

This study was a very large metanalysis of over 40 studies with 35,548 participants that looked at the effect of different diets on heart disease outcomes. The study identified two diets that significantly reduced the risk of heart disease. There are other diets that might reduce the risk of heart disease, but their benefits have not been proven by high quality clinical studies. They are merely pretenders.

The Dangers Of Processed Foods

In previous issues of “Health Tips From the Professor” I have shared articles showing that diets high in processed foods are associated with an increased risk of obesity, diabetes, and heart disease. But the story keeps getting worse. Here are two articles on recent studies about processed foods that appeared in “Health Tips From The Professor” in the last two years.

Why Does Processed Food Make You Fat? We already know that eating a lot of highly processed food is likely to make us fat. But what is it about processed food that makes us fat? In this article I review a recent study that answers that question.

This study is interesting for two reasons.

It identifies the characteristics of processed foods that make us want to eat more.

It identifies some minimally processed foods that have the same characteristics and suggests we should choose minimally processed foods wisely. Simply put, knowledge is power. We may want to avoid minimally processed foods that have the same obesity-inducing characteristics as processed foods.

Do Processed Foods Cause Cancer? Previous studies have shown that processed food consumption is associated with a higher risk of obesity, diabetes, and heart disease. Can it get any worse? In this article I review a recent study that shows processed food consumption is associated with an increased risk of several kinds of cancer.

Maintaining Muscle Mass As We Age

As we age, we begin to lose muscle mass, a process called sarcopenia. Unless we actively resist loss of muscle mass it will eventually impact our quality of life and our health.

We can prevent this loss of muscle mass with resistance exercise, adequate protein intake, and adequate intake of the amino acid leucine. Previous studies have shown people over 50 need more of each of these to maintain muscle mass, but the amount they need has been uncertain until now. Three recent studies have given seniors better guidelines for maintaining muscle mass.

Can You Build Muscle In Your 80s? In this article I review a recent study that enrolled a group of octogenarians in a high-intensity exercise program to see if they could gain muscle mass. They were able to increase their muscle mass, but the intensity of the exercise required may surprise you.

Optimizing Protein Intake For Seniors. In this article I review two recent studies that looked at the amount, timing, and kind of protein needed for seniors in their 60s and 70s to maximize gain in muscle mass.

How Much Leucine Do Seniors Need? In this article I review a recent study that determined the amount of leucine seniors in their 70s need to optimize gains in muscle mass and strength.

The Benefits And Risks Of Supplementation

If you listen to Big Pharma or the medical profession, you hear a lot about the “risks” of supplementation and very little about the benefits. In “Health Tips From the Professor” I try to present a more balanced view of supplementation by sharing high-quality studies showing benefit from supplementation and studies that put the supposed risks into perspective.

The Good News About Omega-3s and Stroke. Multiple studies have shown that omega-3 supplementation reduces the risk of ischemic strokes (strokes caused by a blood clot). But it has been widely assumed they might increase the risk of hemorrhagic strokes (strokes caused by bleeding). In this article I review a meta-analysis of 29 clinical studies with 183,000 participants that tested that assumption.

How Much Omega-3s Are Best For Blood Pressure? Multiple studies have shown that omega-3 supplementation can reduce high blood pressure. But the doses used vary widely from one study to the next. In this article I review a meta-analysis of 71 double-blind, placebo-controlled clinical studies that determined the optimal dose of omega-3s for controlling blood pressure.

Omega-3 Supplements Are Safe. As I said above, it has been widely assumed that omega-3 supplementation increases the risk of bleeding and hemorrhagic stroke. In this article I review the definitive study on this topic. More importantly, it reveals which omega-3 supplements might increase bleeding risk and which do not.

Are Calcium Supplements Safe? Big Pharma and the medical profession have been warning us that calcium supplements may increase heart disease risk. In this article I review the definitive study on this topic.

Prenatal Supplements

If you are pregnant or thinking of becoming pregnant, your health professional has likely recommended a prenatal supplement. You probably assume that prenatal supplements provide everything you need for a healthy pregnancy. Unfortunately, recent research has shown that assumption is not correct.

Is Your Prenatal Supplement Adequate? In this article I review a study that should serve as a wakeup call for every expectant mother. It showed that most prenatal supplements were woefully inadequate for a healthy pregnancy.

What Nutrients Are Missing In Prenatal Supplements? In this article I review a study that identified additional nutrients that are missing in most prenatal supplements.

Prenatal Supplements Strike Out Again. In this article I review a study that looked at the diet of pregnant women to determine their needs and compared that to the nutrients found in prenatal supplements. Once again, most prenatal supplements were woefully inadequate. Is it, “Three strikes and you are out”?

Exercise

Walking Your Way To Health. We have been told that walking is good for our health. But how many steps should you take, how fast should you walk, and does it matter whether these steps are part of your daily routine or on long hikes? In this article I review a study that answers all these questions.

Which Exercise Is Best For Reducing Blood Pressure? If you have high blood pressure, you have probably been told to exercise more. But which exercise is best? In this article I review a study that answers that question. And the answer may surprise you.

Did You Know?

If you have been reading “Health Tips From the Professor” for a while, you probably know that I enjoy poking holes in popular myths. Here are two new ones I deflated in past two years.

Is Low Alcohol Consumption Healthy? You have probably heard that low alcohol intake (that proverbial glass of red wine) is good for you. But is that true? In this article I review a recent study that shows that myth was based on faulty interpretation of the data and provides a more nuanced interpretation of the data.

Is HDL Good For Your Heart? You have been told that increasing your HDL levels reduces your risk of heart disease so many times it must be true. But is it? In this article I review HDL metabolism and a recent study to provide a more nuanced interpretation of the relationship between HDL and heart disease risk.

How To Talk With Your Doctor About Cancer

Because of my years in cancer research, I am often asked whether someone should follow their oncologist’s advice and go on a recommended chemotherapy or radiation regimen. Of course, it would be unethical for me to provide that kind of advice.

In this article I tell you the questions to ask your oncologist about the prescribed treatment regimen, so you can make an informed decision. However, I also recommend you only ask these questions if you can handle the answers.

The Bottom Line

I have just touched on a few of my most popular articles above. You may want to scroll through these articles to find ones of interest to you that you might have missed over the last two years. If you don’t see topics that you are looking for, just go to https://chaneyhealth.com/healthtips/ and type the appropriate term in the search box.

In the coming years, you can look for more articles debunking myths, exposing lies and providing balance to the debate about the health topics that affect you directly. As always, I pledge to provide you with scientifically accurate, balanced information that you can trust. I will continue to do my best to present this information in a clear and concise manner so that you can understand it and apply it to your life.

Final Comment: You may wish to share the valuable resources in this article with others. If you do, then copy the link at the top and bottom of this page into your email. If you just forward this email and the recipient unsubscribes, it will unsubscribe you as well.

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

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

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

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

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

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About The Author

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

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.

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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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.

Are Omega-3 Supplements Safe?

July 9, 2024 by Dr. Steve Chaney

The Flaws And Blind Spots In This Study

Author: Dr. Stephen Chaney

Has the omega-3 pendulum swung again? The recent headlines are downright scary. For example:

“Fish Oil May Increase the Risk of Stroke and Heart Conditions.”

“Fish Oil Supplements May Cause Harm, Study Finds. Is It Time to Ditch Them?”

“Fish Oil Supplements May Lead to Heart Problems”.

“Regular Use of Fish Oil Supplements Might Increase, Rather Than Lessen, The Risk of First Time Heart Disease and Stroke Among Those in Good Cardiovascular Health.”

Yikes! That sounds bad. Should we be thinking about giving up our omega-3 supplements?

But wait. Just a few weeks earlier we were reading headlines about the benefits and lack of side effects from omega-3 supplements. That’s confusing. Which headlines are correct?

To answer these questions:

I will review the study (G Chen et al, BMJ Medicine 2024; 3e000451.doi.10.1136/bmjmed-2022-000451) behind the headlines.

I will point out the flaws and blind spots in the study.

I will strip away the hyperbole and put the headlines into perspective.

How Was The Study Done?

The investigators made use of data from the UK Biobank Study. The UK Biobank Study is a large, long-term study in the United Kingdom which was designed to investigate the contributions of genetic predisposition and environmental exposure [including diet and supplementation] to the development of disease.

The UK Biobank Study enrolled 502,461 participants, aged 40-69 years, between January 1^st, 2006 and December 31^st, 2010. Participants were followed from entry into the program until March 31^st 2021, an average of 11.9 years.

The current study excluded any participants who had a diagnosis of atrial fibrillation, heart failure, heart attack, stroke, or cancer at entry into the study, leaving 415,737 participants.

The participants were:

55% women.
Average age of 56 years, with 83.4% of them below 65 years old at entry into the study.
94.5% white.

The study was designed in a unique manner, in that it was designed to test the effect of omega-3 supplements on 6 specific transitions:

Primary prevention. This measured the transition of healthy (no diagnosed heart disease) people to either atrial fibrillation, major cardiovascular events, or death.

Secondary prevention. This measured the transition from atrial fibrillation to either major cardiovascular events or death.

Tertiary prevention. This measured the transition from major cardiovascular events to death.

Major cardiovascular events were further broken down to heart attacks, stroke and heart failure.

Participants were asked whether they used fish oil supplements when they entered the study and were categorized as either regular users or non-users. [Note: The users were not asked the dose or brand of fish oil supplements they used.]

Deaths were obtained from the national death registry and disease diagnosis from the National Health Service.

Are Omega-3 Supplements Safe?

Here is what the study found.

Primary Prevention – For healthy individuals (defined as having no diagnosed heart disease) using omega-3 supplements for an average of 11.9 years:

Increased the risk of atrial fibrillation by 13%.

Did not affect the risk of major cardiovascular events and death were unaffected by omega-3 supplementation.

When major cardiovascular events were broken down to their component parts, omega-3 supplementation:

- Decreased the risk of heart failure by 8%.

- Increased the risk of stroke by 5% (this was just barely statistically significance).

- Did not affect the risk of heart attack.

Secondary Prevention – For individuals with atrial fibrillation omega-3 supplementation:

Decreased the risk of major cardiovascular events by 9%.

Decreased the risk of death by 8%.

When major cardiovascular events were broken down into their component parts, omega-3 supplementation:

Decreased the risk of heart attacks by 15%.

Had no effect on the risk of stroke or heart failure.

Tertiary Prevention – For people who suffered major cardiovascular events during the study omega-3 supplementation:

Decreased the risk of death by 8%.

Since this is a very complex set of data, I have coded positive results in green and negative results in red.

And as if these complexities were not enough, when the investigators broke these effects down by population groups:

Omega-3 supplementation decreased the transition from healthy to death for men (7% decrease) and participants older than 65 (9% decrease).

I will discuss the significance of these observations below.

The authors concluded, “Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for [reducing] progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death.”

In short, they were suggesting that omega-3 supplements should be avoided by the general population because they have no positive benefits and might increase the risk of atrial fibrillation and stroke. But omega-3 supplements may be useful for those who already have heart disease.

Some of the articles you may have read about the study repeated this message. Others just emphasized the negative aspects of the study.

But is this message accurate? Let me start by discussing the flaws, blind spots, and hidden data in this study. Then I will summarize the 3 key findings of the study and tell you what they mean for you.

The Flaws, Blind Spots, And Hidden Data In This Study

Flaws: As I said above, there were two major flaws in the study.

Flaw #1: The study did not identify the dose of supplement used. This is important because the increased risk of atrial fibrillation and stroke is primarily seen in clinical trials using high dose omega-3 supplements.

Flaw #2: This was an association study which cannot prove cause and effect. However, the authors of this study reported it as showing that omega-3 supplement use caused atrial fibrillation and stroke – and all the news reports on the study have repeated that claim.

Flaw #3: Other experts have pointed out that the authors inflated the risks associated with omega-3 supplementation by reporting relative risk rather than absolute risk. Let me try to simplify the distinction.

The risk of atrial fibrillation was 4.24% in the non-supplement users and 4.80% in the omega-3 supplement users. That is an absolute increase in risk of 0.56% (4.80% – 4.24%). This is the increase in risk you actually experience. In contrast, 4.80% is 13% greater than 4.24%, which is how relative risk is calculated.

In response to the questions you are probably thinking:

Yes, this is a perfect example of the Mark Twain quote, “There are lies. There are damn lies. And then there are statistics.”

Yes, all the percentages reported in this study are based on relative risk and are, therefore, inflated. However, I do not have access to their data, so I cannot tell you the absolute risk associated with their other observations.

Blind Spots: In their paper the investigators recommended against the use of omega-3 supplements to prevent heart disease because their data showed:

No benefit of omega-3 supplementation for preventing major cardiovascular events and deaths in a healthy population.

But did suggest an increased risk of atrial fibrillation and stroke in that same population.

However, their blind spot was in underestimating the difficulty of showing the benefit of any intervention in a healthy population. The example I always use is statin drugs. Statin Drugs:

Dramatically reduce the risk of a second heart attack and/or death in people who have already had a heart attack.

Reduce the risk of heart attacks in people who are at high risk of heart attacks.

Cannot be shown to reduce the risk of heart attacks in a healthy population.

This study suggests that omega-3 supplements are no different. In this study, omega-3 supplements:

Reduced the risk of death in people who had already experienced a major cardiovascular event like a heart attack or stroke.

Reduced the risk of major cardiovascular events and death in people with atrial fibrillation, which puts them at high risk for a heart attack or stroke.

Could not be shown to reduce the risk of major cardiovascular events or deaths in a healthy population.

Hidden Data: There are some important data that were buried in the text and supplemental figures but were ignored in the concluding remarks of this study and all the articles written about it. For example:

The original study and all articles written about the study reported that omega-3 supplementation increased the risk of stroke in otherwise healthy individuals but ignored the observation that omega-3 supplementation decreased the risk of heart failure in that same group.

The second example of hidden data likely represents another blind spot of the authors. They concluded that omega-3 supplementation had no benefit for healthy individuals without asking whether omega-3 supplements might benefit higher-risk subpopulations within this group. To help you understand this statement let me start by giving you some perspective.

As I said above, statin drugs cannot be shown to reduce the risk of heart attacks in a healthy population. But when you include people at high risk of heart disease with healthy people in the dataset, you start to see a reduced risk of heart attacks.

Similarly, with supplements you often see no benefits with the general population, which is what is usually reported in the media. But when you look at higher risk groups within that population, the benefits of supplementation emerge.

This study is no different:

For healthy individuals, omega-3 supplementation had no effect on deaths during the 12-year follow-up period.

However, omega-3 supplementation reduced the risk of death by 9% for both men and people ≥ 65. These represent two groups with elevated risk of heart disease within the otherwise healthy population.

Once again, these data were completely ignored.

What Does This Study Mean For You?

This study made 3 major points:

Point #1: Let me start with the one you’ve heard the most about. The risk of atrial fibrillation and stroke associated with omega-3 supplementation is real. We should not ignore it.

But what this study and most of the reports on the study didn’t tell you is that the risk is dose dependent. The risk is primarily seen with high doses of omega-3s. While no one has done a comprehensive dose response analysis, I can tell you that these side effects are:

Seldom reported in clinical studies at doses of 1 gm/day or less.
Sometimes reported in clinical studies at doses of ≥2 gm/day.
Frequently reported in clinical studies at doses of ≥4 gm/day.

However, atrial fibrillation and stroke occur in a very small percentage of omega-3 users, even at 4 gm/day. At this point we have no idea why some people are susceptible to these side effects and others are not. More research in this area is clearly needed.

Until we know more about who is at risk, my recommendation for people who are trying to reduce the risk of heart disease is to rely on something called the Omega-3 Index to determine your individual omega-3 needs rather than using high-dose omega-3 supplements.

The Omega-3 Index measures the amount of omega-3 fatty acids in your tissues. It is determined by the amount of omega-3s you consume and how you metabolize them, so it is individualized to you.

An Omega-3 Index of 4% is associated with a high risk of heart disease, while an Omega-3 Index of 8% is associated with a low risk of heart disease. There is no evidence that more than 8% provides additional benefit.

Most importantly, it only takes 1-1.6 gm/day of omega-3s to raise your Omega-3 Index from 4% to 8%. At these doses your risk of atrial fibrillation and stroke is extremely small.

For example, a recent meta-analysis of 29 studies with a total of 183,292 participants reported that people with an 8% Omega-3 Index had:

Decreased risk of ischemic stroke (stroke due to blood clots) with no detectable increased risk of hemorrhagic stroke (stroke due to bleeding), and…

No detectable increased risk of atrial fibrillation.

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. Some people go from 4% to 8% more rapidly than others, so you may need to repeat the test several times to optimize your Omega-3 Index.

If your health professional doesn’t have access to the Omega-3 Index test, you can order it from https://omegaquant.com (I have no financial stake in this company, but I know it as a reputable source of the Omega-3 Index test).

Does The Professor Plan To Reduce His Intake Of Omega-3 Fatty Acids? Three weeks ago, I shared that my wife and I have been taking around 3 gm/day of omega-3 supplements for the past 40 years. Now that the association of atrial fibrillation and stroke with high dose omega-3 intake has been firmly established, some of you may be wondering whether we plan to decrease our intake of omega-3 supplements.

The answer is, “No”. Remember that the increased risk of atrial fibrillation and stroke is only seen for a small subset of people taking high-dose omega-3 supplements. If we were part of that subset, we would likely have experienced one of those side effects by now.

However, if you are considering omega-3 supplementation for the first time, you don’t know whether you are part of that subset or not. So, my advice remains the same. Rely on optimizing your Omega-3 Index rather than high-dose omega-3 supplementation.

Point #2: Healthy individuals (those with no symptoms of heart disease) do not benefit from omega-3 supplementation. As I pointed out above, this ignores data from their study, namely.

Omega-3 supplementation reduced the risk of heart failure in healthy subjects.

Omega-3 supplementation reduced the risk of death in higher risk groups within the healthy population (namely men and people 65 and older).

As I discussed above, this is a pattern seen with statin drugs and most nutritional supplements. Simply put, you can’t show any benefit of statin drugs or most nutritional supplements in a “healthy” population, but you can show benefit when you focus on higher risk individuals within the “healthy” population.

The problem, of course, is that most of us don’t really know whether we are “healthy” or not. For millions of Americans the first indication that they are at risk from heart disease is sudden death from a heart attack or stroke.

With that in mind, I will leave the decision about whether you want to supplement with omega-3s up to you. But if you decide to supplement, I recommend you optimize your Omega-3 Index rather than using a high dose omega-3 supplement.

Point #3: People with heart disease benefit from omega-3 supplementation. This recommendation is becoming non-controversial, so I won’t comment further other than to say high dose omega-3 supplements are probably not needed unless prescribed by your health professional.

The Bottom Line

You have been asking me about recent headlines saying that omega-3 supplements may increase rather than decrease the risk of heart disease. So, I analyzed the study behind the headlines. The study makes 3 claims:

Omega-3 supplements increase the risk of atrial fibrillation and stroke when taken by healthy people.

Omega-3 supplements are of no benefit for healthy individuals.

Omega-3 supplements are beneficial for people who have heart disease.

In the article above I review the flaws, blind spots, and hidden data in the article and discuss what it means for you.

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

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

______________________________________________________________________________

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

Do Omega-3s Improve Recovery From A Heart Attack?

March 26, 2024 by Dr. Steve Chaney

Where Do We Go From Here?

Author: Dr. Stephen Chaney

Despite years of controversy, the benefits of omega-3s remain an active area of research. Over the next few weeks, I will review several groundbreaking omega-3 studies. This week I will focus on omega-3s and heart health.

I don’t need to tell you that the effect of omega-3s on heart health is controversial. One month a new study is published showing an amazing health benefit from omega-3 supplementation. A month or two later another study comes up empty. It finds no benefit from omega-3 supplementation.

That leads to confusion. On one hand you have websites and blogs claiming that omega-3s are a magic elixir that will cure all your ills. On the other hand, there are the naysayers, including many health professionals, claiming that omega-3 supplements are worthless.

I have discussed the reasons for the conflicting results from omega-3 clinical studies in previous issues of “Health Tips From the Professor”. You can go to https://www.chaneyhealth.com/healthtips/ and put omega-3s in the search box to read some of these articles.

Or if you prefer, I have also put together a digital download I call “The Omega-3 Pendulum” which briefly summarizes all my previous articles. It’s available on my Chaney Health School Teachable website.

Today I will discuss a study (B Bernhard et al, International Journal of Cardiology, 399; 131698, 2024) that asks whether 6 months of high dose omega-3 supplementation following a heart attack reduced the risk of major cardiovascular events over the next 6.6 years.

You might be wondering why the study didn’t just look at the effect of continuous omega-3 supplementation for 6 years following a heart attack. There are two very good reasons for the design of the current study.

1) The investigators wanted to do a double blind, placebo controlled clinical trial, the gold standard for clinical studies. However, that kind of study is impractical for a multi-year clinical trial. It would be prohibitively expensive, and patient compliance would be a big problem for a study that long.

2) The months immediately after a heart attack are critical in determining the long-term recovery of that patient. There is often a period of massive inflammation following a heart attack. And that can lead to further damage to the heart and reclosing of the arteries leading to the heart, both of which increase the risk of future adverse cardiac events.

Previous studies have shown that high dose omega-3s immediately following a heart attack can reduce inflammation and damage to the heart. However, those studies did not determine whether the cardioprotective effect of omega-3 supplementation immediately after a heart attack lead to improved long-term outcomes, something this study was designed to determine.

How Was The Study Done?

The investigators enrolled 358 patients who had suffered a heart attack from three Boston area medical centers between June 2008 and August 2012.

The patient demographics were:

Gender = 70% female.
Average age = 59
Average BMI = 29 (borderline obese).
Patients with high blood pressure = 64%
Patients with diabetes = 25%.

The patients were divided into two groups. The first group received capsules providing 4 gm/day of EPA, DHA, and other naturally occurring omega-3 fatty acids. The other group received a placebo containing corn oil. This was a double-blind study. Neither the patients nor the investigators knew which patients received the omega-3 fatty acids and which ones received the placebo.

The patients were instructed to take their assigned capsules daily for 6 months. At the beginning of the study, blood samples were withdrawn to determine the percentage of omega-3s in the fatty acid content of their red cell membranes (something called omega-3 index). Patients were also tested for insulin resistance and given a complete cardiovascular workup. This was repeated at the end of the 6-month study.

[Note: Previous studies have shown that an omega-3 index of 4% or lower is associated with high risk of heart disease, and an omega-3 index of 8% or above is associated with a low risk of heart disease.]

At 2-month intervals the patients were contacted by staff using a scripted interview to determine compliance with the protocol and their cardiovascular health. Once the 6 months of omega-3 supplementation was completed, the patients were followed for an additional 6.6 years. They were contacted every 6 months for the first 3 years and yearly between 3 years and 6 years.

The investigators quantified the number of major cardiac events (defined as recurrent heart attacks, the necessity for recurrent coronary artery bypass grafts, hospitalizations for heart failure, and all-cause deaths) for each patient during the 6.6-year follow-up period.

Patients in both groups were treated according to current “standard of care” protocols which consisted of diet and exercise advice and 5-6 drugs to reduce future cardiovascular events.

Do Omega-3s Improve Recovery From A Heart Attack?

When the investigators looked at the incidence of adverse cardiac events during the 6.6-year follow-up period, there were three significant findings from this study.

1) There were no adverse effects during the 6-month supplementation period with 4 gm/day of omega-3s. This is significant because a previous study with 4 gm/day of high purity EPA had reported some adverse effects which had led some critics to warn that omega-3 supplementation was dangerous. More study is needed, but my hypothesis is that this study did not have side effects because it used a mixture of all naturally occurring omega-3s rather than high purity EPA only.

However, this could also have been because of the way patients were screened before entering this study. I will discuss this in more detail below.

2) When the investigators simply compared the omega-3 group with the placebo group there was no difference in cardiovascular outcomes between the two groups. This may have been because this study faced significant “headwinds” that made it difficult show any benefit from supplementation. I call them “headwinds” rather than design flaws because they were unavoidable.

- It would be unethical to deny the standard of care to any patient who has just had a heart attack. That means that every patient in a study like this will be on multiple drugs that duplicate the beneficial effects of omega-3 fatty acids – including lowering blood pressure, lowering triglycerides, reducing inflammation, and reducing plaque buildup and blood clot formation in the coronary arteries.

That means that this study, and studies like it, cannot determine whether omega-3 fatty acids improve recovery from a heart attack. They can only ask whether omega-3 fatty acids have any additional benefit for patients on multiple drugs that duplicate many of the effects of omega-3 fatty acids. That significantly reduces the risk of a positive outcome.

- As I mentioned above, it would have been impractical to continue providing omega-3 supplements and placebos during the 6.6-year follow-up.

And the study was blinded, meaning that the investigators did not know which patients got the omega-3s and which patients got the placebo. That meant the investigators could not advise the omega-3 supplement users to continue omega-3 supplementation during the follow-up period.

Consequently, the study could only ask if 6 months of high-dose omega-3 supplementation had a measurable benefit 6.6 years later. I, for one, would be more interested in knowing whether lower dose omega-3 supplementation continued for the duration of this study reduced the risk of major coronary events.

3) When the investigators compared patients who achieved a significant increase in their omega-3 index during the 6-month supplementation period with those who didn’t, they found a significant benefit of omega-3 supplementation.

This was perhaps the most significant finding from this study.

If the investigators had stopped by simply comparing omega-3 users to the placebo, this would have been just another negative study. We would be wondering why it did not show any benefit of omega-3 fatty acid supplementation.

However, these investigators were experts on the omega-3 index. They knew that there was considerable individual variability in the efficiency of omega-3 uptake and incorporation into cell membranes. In short, they knew that not everyone taking a particular dose of omega-3s will achieve the same omega-3 index.

And that is exactly what they saw in this study. All the patients in the 6-month omega-3 group experienced an increase in omega-3 index, but there was considerable variability in how much the omega-3 index increased over 6 months.

So, the investigators divided the omega-3 group into two subgroups – ones whose omega-3 index increased by ≥ 5 percentage points (sufficient to move those patients from high risk of heart disease to low risk) and ones whose omega-3 index increased by less than 5 percentage points.

When the investigators compared patients with ≥ 5% increase in omega-3 index to those with <5% increase in omega-3 index:

Those with an increase in omega-3 index of ≥ 5% had a 2.9% annual risk of suffering major adverse cardiac events compared to a 7.1% annual risk for those with an increase of <5%.

That’s a risk reduction of almost 60%, and it was highly significant.

The authors concluded, “In a long-term follow-up study, treatment with [high dose] omega-3s for 6 months following a heart attack did not reduce adverse cardiac events compared to placebo. However, those patients who were treated with omega-3s and achieved ≥ 5% rise in omega-3 index experienced a significant reduction of adverse cardiac events after a median follow-up period of 6.6 years…Additional studies are needed to confirm this association and may help identify who may benefit from omega-3 fatty acid treatment following a heart attack.”

What Does This Study Mean For You?

I should start by saying that I do not recommend 4 gm/day of omega-3 fatty acids following a heart attack without checking with your doctor first.

If you are on a blood thinning medication, the dose of either the medication or the omega-3 supplement may need to be reduced to prevent complications due to excess bleeding.

In addition, the investigators excluded patients from this study who might suffer adverse effects from omega-3 supplementation. This is a judgement only your doctor can make.

With that advice out of the way, the most important takeaway from this study is that uptake and utilization of omega-3 fatty acids varies from individual to individual.

The omega-3 index is a measure of how well any individual absorbs and utilizes dietary omega-3s. And this study shows that the omega-3 index is a much better predictor of heart health outcomes than the amount of omega-3 fatty acids a person consumes.

This is not surprising because multiple studies have shown that the omega-3 index correlates with heart health outcomes. It may also explain why many studies based on omega-3 intake only have failed to show a benefit of omega-3 supplementation.

Vitamin D supplementation is a similar story. There is also considerable variability in the uptake of vitamin D and conversion to its active form in the body. 25-hydroxy vitamin D levels in the blood are a marker for active vitamin D. For that reason, I have long recommended that you get your 25-hydroxy vitamin D level tested with your annual physical and, with your doctor’s help, base the dose of the vitamin D supplement you use on that test.

This study suggests that we may also want to request an omega-3 index test and use it to determine the amount of supplemental omega-3s we add to our diet.

Where Do We Go From Here?

The idea that we need to use the omega-3 index to determine the effectiveness of the omega-3 supplement we use is novel. As the authors suggest, we need more studies to confirm this effect. There are already many studies showing a correlation of omega-3 index with heart health outcomes. But we need more double blind, placebo-controlled studies like this one.

More importantly, we need to understand what determines the efficiency of supplemental fatty acid utilization so we can predict and possibly improve omega-3 utilization. The authors suggested that certain genetic variants might affect the efficiency of omega-3 utilization. But the variability of omega-3 utilization could also be affected by:

Diet, especially the presence of other fats in the diet.

Metabolic differences due to obesity and diseases like diabetes.

Gender, ethnicity, and age.

Design of the omega-3 supplement.

We need much more research in these areas, so we can personalize and optimize omega-3 supplementation on an individual basis.

The Bottom Line

A recent study asked whether high dose omega-3 supplementation for 6 months following a heart attack reduced major cardiac events during the next 6.6 years.

When they simply compared omega-3 supplementation with the placebo there was no effect of omega-3 supplementation on cardiac outcomes.

However, when they based their comparison on the omega-3 index (a measure of how efficiently the omega-3s were absorbed and incorporated into cell membranes), the group with the highest omega-3 index experienced a 60% reduction in adverse cardiac events over the next 6.6 years.

This is consistent with multiple studies showing that the omega-3 index correlates with heart health outcomes.

More importantly, this study shows there is significant individual variation in the efficiency of omega-3 absorption and utilization. It also suggests that recommendations for omega-3 supplementation should be based on the omega-3 index achieved rather than the dose or form of the omega-3 supplement.

For more information on this study and what it means for you read the article above.

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

______________________________________________________________________________

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

Which Supplements Are Good For Your Heart?

February 7, 2023 by Dr. Steve Chaney

How Should You Interpret This Study?

Author: Dr. Stephen Chaney

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

The Good News is that between 2009 and 2019:

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

The Bad News is that:

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

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

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

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

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

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

How Was This Study Done?

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

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

884 randomized, placebo-controlled clinical studies…

Of 27 types of micronutrients…

With a total of 883,627 patients…

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

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

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

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

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

Which Supplements Are Good For Your Heart?

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

Omega-3 Fatty Acids:

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

Folic Acid:

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

Coenzyme Q10:

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

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

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

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

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

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

How Should You Interpret This Study?

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

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

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

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

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

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

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

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

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

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

Coenzyme Q10:

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

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

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

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

Omega-3s:

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

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

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

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

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

Folic acid:

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

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

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

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

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

Vitamins E and D:

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

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

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

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

β-carotene:

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

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

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

The Bottom Line

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

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

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

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

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

For more details on this study and what it means for you, read the article above.

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

Omega-3s And Congestive Heart Failure

May 3, 2022 by Dr. Steve Chaney

We Have Been Asking The Wrong Questions

Author: Dr. Stephen Chaney

Today’s Health Tip is a follow-up to the article I published last month on omega-3s and heart disease risk. In that article I pointed out the reasons why studies of the effect of omega-3s and heart disease risk have been so confusing.

One of the reasons is that many of the studies have been asking the wrong questions.

They were asking whether omega-3s reduced the risk of heart disease for everyone. Instead, they should have been asking who benefited from omega-3 supplementation.

They were asking whether omega-3s reduced the risk of all forms of heart disease combined. Instead, they should have been asking whether omega-3s reduced the risk of specific kinds of heart disease.

I also discussed a large clinical trial, the VITAL study, that was designed to answer those two questions.

The study I will describe today (L Djoussé et al, JACC Heart Failure, 10: 227-234, 2022) mined the data from the VITAL study to evaluate the effect of omega-3 supplementation on congestive heart failure, a form of heart disease that was not discussed in the VITAL study.

Everything You Need To Know About Congestive Heart Failure

Congestive heart failure is a killer. The term congestive heart failure simply means that your heart no longer pumps blood well. The initial symptoms are relatively non-specific and include things like.

Shortness of breath.
Fatigue and weakness.
Reduced ability to exercise.
Rapid or irregular heartbeat.
Persistent cough or wheezing.

However, as it progresses, the symptoms get much worse. Fluid builds up in your tissues.

Fluid buildup in your legs, ankles, and feet can make it difficult to walk.

Fluid buildup in your lungs makes it difficult to breathe. In advanced stages it can feel like you are drowning in a room full of air.

According to the CDC:

4 million Americans have congestive heart failure (CHF).

- It leads to ~380,000 deaths/year.

83% of patients diagnosed with CHF will be hospitalized at least once.

- 67% will be hospitalized two or more times.

CHF costs >$30 billion per year in health care costs and lost wages.

The risk of congestive heart failure is not spread evenly across the American population. Black Americans and Americans with type 2 diabetes are at increased risk.

According to the Framingham Heart Study:

Type 2 diabetes increases the risk of CHF 2-fold in men and 5-fold in women. The reasons are not entirely clear. However:

- High blood sugar is thought to either damage cells in heart muscle, weakening it, or damage small blood vessels within the heart, making it more difficult for the heart to pump blood.

- Some diabetes drugs that lower blood sugar also appear to increase the risk of congestive heart failure.

According to the CDC:

Black Americans are 2-fold more likely to develop CHF than White Americans. Again, the reasons are not clear. However:

- Some experts feel it could be due to the higher incidence of untreated high blood pressure in Black Americans.

In summary:

Congestive heart failure is a serious disease. Its symptoms affect your quality of life, and it can lead to hospitalizations and death.

Black Americans and Americans with type 2 diabetes are at higher risk of developing congestive heart failure.

How Was The Study Done?

The VITAL study, from which these data were extracted, was a placebo-controlled clinical trial designed to measure the effects of 1,000 mg omega-3 supplementation on the risk of developing heart disease. It enrolled 25,871 Americans aged 55 years or older and followed them for an average of 5.3 years.

The participants enrolled in the VITAL study represented a cross-section of the American population. Most were at low risk of heart disease, but there were subsets of the study group who were at higher risk of heart disease. A strength of the VITAL study was that it was designed so the high-risk subgroups could be evaluated separately.

The current study utilized data from the VITAL study to look at the effect of omega-3 supplementation on hospitalizations due to congestive heart failure. It also evaluated the effect of type 2 diabetes and race on the risk of hospitalizations.

Omega-3s And Congestive Heart Failure

When the investigators looked at the whole population, most of whom were at low-risk of congestive heart failure, they did not see any effect of omega-3 supplementation on the risk of hospitalizations due to congestive heart failure.

However, when they looked at high risk groups, the story was much different.

In patients with type-2 diabetes:

Omega-3 supplementation reduced the risk of the initial hospitalization for congestive heart failure by 31%

Omega-3 supplementation reduced the risk of multiple hospitalizations due to congestive heart failure by 47%.

The effect of omega-3 supplementation on hospitalizations was greatest for the Black participants in the study.

In the words of the authors, “Our data show beneficial effects of omega-3 fatty acid supplements on the incidence of heart failure hospitalizations in participants with type 2 diabetes but not in those without type 2 diabetes, and such benefit appeared to be stronger in Black participants with type 2 diabetes.”

We Are Asking The Wrong Questions

As I said above, there is so much confusion about the effect of omega-3s on heart disease because we scientists have been asking the wrong questions:

We have been asking whether omega-3s reduce the risk of heart disease for everyone. Instead, we should have been asking who benefits from omega-3 supplementation.

We have been asking whether omega-3s reduced the risk of all forms of heart disease combined. Instead, we should have been asking whether omega-3s reduced the risk of specific kinds of heart disease.

In my “Health Tip” last month I discussed a large clinical study, the VITAL study, that was specifically designed to answer the right questions. Like so many other studies it found that omega-3 supplementation did not significantly reduce the risk of all kinds of heart disease for everyone.

However, what it did find was more important than what it did not find:

When they looked at the effect of omega-3s on heart disease risk in high-risk groups, they found that major cardiovascular events were reduced by:

- 26% in African Americans.

- 26% in patients with type 2 diabetes.

- 17% in patients with a family history of heart disease.

- 19% in patients with two or more risk factors of heart disease.

When they looked at the effect of omega-3s on heart disease risk in people with low omega-3 intake, they found that omega-3 supplementation reduced major cardiovascular events by:

- 19% in patients with low fish intake.

When they looked at the effect of omega-3s on the risk of different forms of heart disease, they found that omega-3 supplementation reduced:

- Heart attacks by 28% in the general population and by 70% for African Americans.

- Deaths from heart attacks by 50%.

- Deaths from coronary heart disease (primarily heart attacks and ischemic strokes (strokes caused by blood clots)) by 24%.

In other words, when they asked the wrong questions, they got the wrong answer. If they had just looked at the effect of omega-3 supplementation on all forms of heart disease for everyone (like most other omega-3 studies), they would have concluded that omega-3s are worthless.

However, when they asked the right questions, they found that omega-3s were very beneficial for high-risk populations and for certain types of heart disease.

The current study utilized the same data to analyze the effect of omega-3 supplementation on hospitalizations due to congestive heart failure. And the results were similar.

If they had asked the wrong question, “Does omega-3 supplementation reduce congestive heart failure hospitalizations for everyone?”, they would have concluded that omega-3 supplementation was worthless.

However, instead they asked, “Does omega-3 supplementation reduce congestive heart failure hospitalizations for certain high-risk groups” and were able to show that omega-3 supplementation significantly reduced congestive heart failure hospitalizations for people with type 2 diabetes and for Blacks.

We need to change the paradigm for clinical studies of supplements. The old paradigm asks the wrong questions. If we really want to know the role of supplementation for our health, we need to start asking the right questions.

The Bottom Line

There is perhaps nothing more confusing to the average person than the “truth” about omega-3 supplementation and heart disease risk. Much of the confusion is because we have been asking the wrong questions:

We have been asking whether omega-3 supplementation reduces the risk of heart disease for everyone. Instead, we should have been asking who benefits from omega-3 supplementation.

We have been asking whether omega-3 supplementation reduces the risk of all forms of heart disease combined. Instead, we should have been asking whether omega-3 supplementation reduces the risk of specific kinds of heart disease.

A recent study on the effect of omega-3 supplementation on hospitalizations due to heart disease is a perfect example.

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.

The Omega-3 Pendulum

April 12, 2022 by Dr. Steve Chaney

Who Benefits Most From Omega-3s?

Author: Dr. Stephen Chaney

If you were around in the 60’s, you might remember the song “England Swings Like a Pendulum Do”. It was a cute song, but it had nothing to do with pendulums. This week I am talking about something that really does resemble a pendulum – the question of whether omega-3s reduce heart disease risk.

There is perhaps nothing more confusing to the average person than the “truth” about omega-3s and heart disease risk. The headlines and expert opinion on the topic swing wildly between “omega-3s reduce heart disease risk” to “omega-3s have no effect on heart disease risk” and back again. To me these swings resemble the swings of a pendulum – hence the title of this article.

Part of the reason for the wild swings is that journalists and most “experts” tend to rely on the latest study and ignore previous studies. Another contributing factor is that most journalists and experts read only the main conclusions in the article abstract. They don’t read and analyze the whole study.

So, in today’s “Health Tips From the Professor” I plan to:

Analyze 3 major studies that have influenced our understanding of the relationship between omega-3 intake and heart disease risk. I will tell you what the experts missed about these studies and why they missed it.

Summarize what you should know about omega-3 intake and your risk of heart disease.

Why Is The Role Of Omega-3s In Preventing Heart Disease So Confusing?

In answering that question, let me start with what I call “Secrets Only Scientists Know”.

#1: Each study is designed to disprove previous studies. That is a strength of the scientific method. But it guarantees there will be studies on both sides of every issue.

Responsible scientists look at all high-quality studies and base their opinions on the weight of evidence. Journalists and less-responsible “experts” tend to “cherry pick” the studies that match their opinions.

#2: Every study has its flaws. Even high-quality studies have unintended flaws. And I have some expertise in identifying unintended flaws.

I published over 100 papers that went through the peer review process. And I was involved in the peer review of manuscripts submitted by other scientists. In the discussion below I will use my experience in reviewing scientific studies to identify unintended flaws in 3 major studies on omega-3s and heart disease risk.

Next, let me share the questions I ask when reviewing studies on omega-3s and heart disease. I am just sharing the questions here. Later I will share examples of how these questions allowed me to identify unintended flaws in the studies I review below.

#1: How did they define heart disease? The headlines you read usually refer to the effect of omega-3s on “heart disease”. However, heart disease is a generic term. In layman’s terms, it encompasses angina, heart attacks, stroke due to blood clots, stroke due brain bleeds, congestive heart failure, impaired circulation, and much more.

Omega-3s have vastly different effects on different forms of heart disease, so it is important to know which form(s) of heart disease the study examined. And if the study included all forms of heart disease, it is important to know whether they also looked at the forms of heart disease where omega-3s have been shown to have the largest impact.

#2: What was the risk level of the patients in the study? If the patients in the study are at imminent risk of a heart attack or major cardiovascular event, it is much easier to show an effect than if they are at low risk.

For example, it is easy to show that statins reduce the risk of a second heart attack in someone who has just suffered a heart attack. These are high-risk patients. However, if you look at patients with high cholesterol but no other risk factors for heart disease, it is almost impossible to show a benefit of statins. These are low-risk patients.

If it is difficult to show that statins benefit low-risk patients, why should we expect to be able to show that omega-3s benefit low-risk patients?

[Note: I am not saying that statins do not benefit low-risk patients. I am just saying it is very difficult to prove they do in clinical studies.]

#3: How much omega-3s are the patients getting in their diet? The public reads the headlines. When the headlines say that omega-3s are good for their hearts, they tend to take omega-3 supplements. When the headlines say omega-3s are worthless, they cut back on omega-3 supplements. So, there is also a pendulum effect for omega-3 intake.

Omega-3s are fats. So, omega-3s accumulate in our cell membranes. The technical term for the amount of omega-3s in our cellular membranes is something called “Omega-3 Index”. Previous studies have shown that:

- An omega-3 index of 4% or less is associated with high risk of heart disease, and…

- An omega-3 index of 8% or more is associated with a low risk of heart disease.

When the omega-3 index approaches 8%, adding more omega-3 is unlikely to provide much additional benefit. Yet many studies either don’t measure or ignore the omega-3 index of patients they are enrolling in the study.

#4: How many and what drugs were the patients taking? Many heart disease patients are taking drugs that lower blood pressure, lower triglycerides, reduce inflammation, and reduce the risk of blood clot formation. These drugs do the same things that omega-3s do. This decreases the likelihood that you can see any benefit from increasing omega-3s intake.

The Omega-3 Pendulum

With all this in mind let’s examine three major double-blind, placebo-controlled studies that looked at the effect of omega-3s on heart disease risk and came to different conclusions. Here is a summary of the studies.

GISSI Study	ASCEND Study	VITAL Study
11,000 participants	15,480 participants	25,871 participants
Followed for 3.5 years	Followed for 7.4 years	Followed for 5.3 years
Europe	USA	USA
Published in 1999	Published in 2018	Published in 2019
Dose = 1 gm/day	Dose = 1 gm/day	Dose = 1 gm/day
20% ↓ in heart disease deaths	No effect on fatal or non-fatal heart attack or stroke	Significant ↓ in some forms of heart disease
45% ↓ in fatal heart attack or stroke – as effective as statins		Significant ↓ in heart disease risk for some patients

At first glance the study designs look similar, so why did these studies give such different results. This is where the unintended flaws come into play. Let’s look at each study in more detail.

The GISSI Study:

The patients enrolled in this study all had suffered a heart attack in the previous 3 months. They were at very high risk of suffering a second heart attack within the next couple of years.

Omega-3 intake was not measured in this study. But it was uncommon for Europeans to supplement with omega-3s in the 90’s. And European studies on omega-3 intake during that period generally found that omega-3 intake was low.

Patients enrolled in this study were generally taking only 2 heart disease drugs, a beta-blocker and a blood pressure drug.

The ASCEND Study:

The patients enrolled in this study had diabetes without any evidence of heart disease. Only 17% of the patients enrolled in the study were at high risk of heart disease. 83% were at low risk. Remember, it is difficult to show a benefit of any intervention in low-risk patients.

The average omega-3 index of patients enrolled in this study was 7.1%. That means omega-3 levels were near optimal at the beginning of the study. Adding additional omega-3s was unlikely to show much benefit.

Most of the patients in this study were on 3-5 heart drugs and 1-2 diabetes drugs which duplicated the effects of omega-3s.

That means this study was asking a very different question. It was asking whether omega-3s provided any additional benefit for patients who were already taking multiple drugs that duplicated the effects of omega-3s.

However, you would have never known that from the headlines. The headlines simply said this study showed omega-3s were ineffective at preventing heart disease.

Simply put, this study was doomed to fail. However, despite its many flaws the authors reported that omega-3s did reduce one form of heart disease, namely vascular deaths (primarily due to heart attack and stroke). Somehow this observation never made it into the headlines.

The VITAL Study:

This study enrolled a cross-section of the American population aged 55 or older (average age = 67). As you might suspect for a cross-section of the American population, most of the participants in this study were at low risk for heart disease. This limited the ability of the study to show a benefit of omega-3 supplementation in the whole population.

However, there were subsets of the group who were at high risk of heart disease (more about that below).

This study excluded omega-3 supplement users The average omega-3 index of patients enrolled in this study was 2.7% at the beginning of the study and increased substantially during the study. This enhanced the ability of the study to show a benefit of omega-3 supplementation.

Participants in this study were only using statins and blood pressure medications. People using more medications were excluded from the study. This also enhanced the ability of the study to show a benefit of omega-3 supplementation.

The authors reported that “Supplementation with omega-3 fatty acids did not result in a lower incidence of major cardiovascular events…” This is what lazy journalists and many experts reported about the study.

However, the authors designed the study so they could also:

Look at the effect of omega-3s on heart disease risk in high-risk groups. They found that major cardiovascular events were reduced by:

- 26% in African Americans.

- 26% in patients with diabetes.

- 17% in patients with a family history of heart disease.

- 19% in patients with two or more risk factors of heart disease.

Look at the effect of omega-3s on heart disease risk in people with low omega-3 intake. They found that omega-3 supplementation reduced major cardiovascular events by:

- 19% in patients with low fish intake.

Look at the effect of omega-3s on the risk of different forms of heart disease. They found that omega-3 supplementation reduced:

- Heart attacks by 28% in the general population and by 70% for African Americans.

- Deaths from heart attacks by 50%.

- Deaths from coronary heart disease (primarily heart attacks and ischemic strokes (strokes caused by blood clots)) by 24%.

In summary, if you take every study at face value it seems like the pendulum is constantly swinging from “omega-3s reduce heart disease risk” to “omega-3s are worthless” and back again. There appears to be no explanation for the difference in results from one study to the next.

However, if you remember that even good studies have unintended flaws and ask the four questions I proposed above, it all makes sense.

How is heart disease defined? Studies looking at heart attack and/or ischemic stroke are much more likely to show a benefit of omega-3s than studies that include all forms of heart disease.

Are the patients at low-risk or high-risk for heart disease? Studies in high-risk populations are much more likely to show a benefit than studies in low-risk populations.

What is the omega-3 intake of participants in the study? Studies in populations with low omega-3 intake are more likely to show a benefit of omega-3 supplementation than studies in populations with high omega-3 intake.

How many heart drugs are the patients taking? Studies in people taking no more than one or two heart drugs are more likely to show a benefit of omega-3 supplementation than studies in people taking 3-5 heart drugs.

When you view omega-3 clinical studies through the lens of these 4 questions, the noise disappears. It is easy to see why these studies came to different conclusions.

Who Benefits Most From Omega-3s?

The answers to this question are clear:

People at high risk of heart disease are most likely to benefit from omega-3 supplementation.

People with low omega-3 intake are most likely to benefit from omega-3 supplementation.

Omega-3 supplementation appears to have the biggest effect on heart attack and ischemic stroke (stroke due to blood clots). Its effect on other forms of heart disease is less clear.

Omega-3 supplementation appears to be most effective at preventing heart disease if you are taking no more than 1 or 2 heart drugs. It may provide little additional benefit if you are taking multiple heart drugs. However, you might want to have a conversation with your doctor about whether omega-3 supplementation might allow you to reduce or eliminate some of those drugs.

What about the general population? Is omega-3 supplementation useful for patients who are at low to moderate risk of heart disease?

If we compare omega-3 studies with statin studies, the answer would be yes. Remember that statins cannot be shown to reduce heart attacks in low-risk populations. However, because they are clearly effective in high-risk patients, the medical community assumes they should be beneficial in low-risk populations. The same argument could be made for omega-3s.

We also need to recognize that our ability to recognize those who are at high risk of heart disease is imperfect. For too many Americans, the first indication that they have heart disease is sudden death!

When I was still teaching, I invited a cardiologist to speak to my class of first year medical students. He told the students, only partly in jest, that he felt statins were so beneficial they “should be added to the drinking water”.

I feel the same way about omega-3s:

Most Americans do not get enough omega-3s in our diet.

Our omega-3 index is usually much closer to 4% (high risk of heart disease) than 8% (low risk of heart disease).

Many of us may not realize that we are at high risk of heart disease until it is too late.

And omega-3s have other health benefits.

For all these reasons, omega-3 supplementation only makes sense.

The Bottom Line

If you take every study at face value, there appears to be no explanation for the difference in results from one study to the next. However, if you recognize that even good studies have unintended flaws and ask four simple questions to expose these flaws, it all makes sense.

For the four questions you should ask when reviewing any omega-3 study and my recommendations for who benefits the most from omega-3 supplementation, 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 Low Omega-3 Intake As Bad For You As Smoking?

August 31, 2021 by Dr. Steve Chaney

What Is The Omega-3 Index And Why Is It Important?

Author: Dr. Stephen Chaney

We already know that smoking is one of the worst things we can do to our bodies. It dramatically increases our risk of cancer, heart disease, diabetes, and lung diseases, including chronic obstructive pulmonary disease (COPD).

It also leads to premature death. People who smoke regularly die 5 years earlier than those who don’t.

That is the bad news. The good news is that smoking is what is called a “modifiable risk factor”. Simply put, that means it is a risk factor we are in control of. The message has been clear for years.

If you don’t smoke, keep it that way.

If you do smoke, stop. If you are a smoker, quitting isn’t easy, but it is worth it. The damage caused by smoking can largely be reversed if you stay off cigarettes long enough.

Obesity and diabetes are also modifiable risk factors that have a huge effect on the risk of both heart disease and premature death. People with diabetes die 4 years earlier than those without diabetes. But obesity and diabetes are harder for most people to reverse than smoking.

Diet is another modifiable risk factor, but, in general, its effect on the risk of heart disease and premature death is not as great as smoking and diabetes. But what if there were one component of diet that had huge effect on both heart disease and premature death?

The long chain omega-3 fatty acids (EPA & DHA) might just fill that bill. We already know they significantly reduce the risk of heart disease (see below), but could they also help us live longer? This study (MI McBurney et al, American Journal of Clinical Nutrition, published online June 16, 2021) was designed to answer that question.

Metabolism 101: What Is The Omega-3 Index And Why Is It Important?

Clinical studies on the benefits of omega-3s have been plagued by the question of how to best measure the omega-3 status of the participants.

You can ask the participants to fill out a dietary survey and calculate how many omega-3-rich foods they are eating, but:

- Dietary recall is notoriously inaccurate. People don’t remember everything they ate and have a hard time estimating portion sizes.

You can measure omega-3 fatty acids in the blood, but:

- Blood levels are transient. Omega-3 fatty acids enter the bloodstream from the intestine and then disappear from blood as they are taken up by the cells.

- Different forms of omega-3s (esters versus acetate, for example) are absorbed from the intestine and taken up by cells at different rates.

You can measure the omega-3 content of cellular membranes. This is the best assay for omega-3 status because:

- The long chain omega-3 fatty acids (EPA and DHA) that have the biggest effect on heart disease risk accumulate in our cell membranes.

- Omega-3 fatty acids are essential (our bodies can’t make them). That means the omega-3 content of our cell membranes reflect the omega-3 content of our diet. This is one of the cases where the saying, “We are what we eat”, is literally true.

- The omega-3 content of our cell membranes is relatively stable. It reflects the omega-3 content of our diet over the last few months.

In theory, you could measure the omega-3 content of cell membranes from any tissues in the body, but red blood cells can easily be obtained by a simple blood draw, so they are the tissue of choice.

A group lead by Dr. William H Harris standardized this measurement by creating something called the Omega-3 Index. Simply put, the Omega-3 Index is the percentage of EPA and DHA in red blood cell membranes.

It turns out that the Omega-3 Index is an excellent indicator of heart disease risk.

An Omega-3 Index of less than 4% is associated with a high risk of heart disease.

An Omega-3 Index of more than 8% is associated with a low risk of heart disease.

But could a low Omega-3 Index also be associated with an increased risk of premature death? This is what the current study was designed to find out.

How Was This Study Done?

The data for this study were obtained from the ongoing Framingham Offspring Heart Study.

To put this statement into perspective, the original Framingham Heart Study began in 1948 in Framingham Massachusetts with the goal of identifying the factors that contributed to heart disease. It was one of the first major studies to identify the role of saturated fats, elevated blood cholesterol, and elevated blood triglycerides on heart disease risk.

The study is continuing today with the second and third generation descendants of the original study participants. It has also been broadened to include other diseases and additional risk factors, such as the Omega-3 Index.

This study selected 2240 participants from the Framingham Offspring study who had no heart disease and also had Omega-3 Index measurements at the beginning of the study. The study then followed them for 11 years. The goal of the study was to compare the Omega-3 Index with the two most potent risk factors for heart disease (smoking and diabetes) in predicting the risk of premature death.

The characteristics of the participants at the beginning of the 11-year study were:

43% male, 57% female.
Average age = 65.
3% were smokers.
8% were diabetic.
Average Omega-3-Index = 5.8%. This is slightly higher than the American average of ~5%.

Is Low Omega-3-Intake As Bad For You As Smoking?

The participants in the study were divided into 5 quintiles based on their Omega-3 Index.

The 20% of the group in the lowest quintile had an Omega-3 Index of <4.2%.

The 20% of the group in the highest quintile had an Omega-3 Index of >6.8%.

First, the scientists running the study did a direct comparison of the top three risk factors on the risk of premature death. Here is what they found.

The group with the lowest average Omega-3 Index died 4.74 years earlier than the group with the highest average Omega-3 Index.

Smokers died 4.73 years earlier than non-smokers.

People with diabetes died 3.90 years earlier than people without diabetes.

That means low omega-3 intake was just as bad for the participants in this study as smoking. Even the authors of the study were surprised by this result. They had expected omega-3 fatty acids to be beneficial, but they had not expected them to be as beneficial as not smoking.

Because omega-3 fatty acid intake and smoking were the two most potent risk factors for premature death, the authors looked at the interaction between the two. They found that the predicted 11-year survival was:

85% for non-smokers with high omega-3 intake.

71% for either…

- Smokers with high omega-3 intake, or…

- Non-smokers with low omega-3 intake.

Only 47% for smokers with low omega-3 intake.

Simply put, this study predicts if you were a 65-year-old smoker with low omega-3 intake, you could almost double your chances of surviving another 11 years by giving up smoking and increasing your omega-3 intake.

In the words of the authors, “Smoking and omega-3 intake seem to be the most easily modified risk factors [for premature death]…Dietary choices that change the Omega-3 index may prolong life.”

The Bottom Line

We know that smoking is deadly, but could low intake of omega-3 fatty acids be just as deadly?

A recent study compared omega-3 intake with the two most potent risk factors (smoking and diabetes) in predicting the risk of premature death. Here is what it found.

The group with the lowest average omega-3 intake died 4.74 years earlier than the group with the highest average omega-3 intake.

Smokers died 4.73 years earlier than non-smokers.

People with diabetes died 3.90 years earlier than people without diabetes.

That means high omega-3 intake was just as beneficial for the participants in this study as not smoking. Even the authors of the study were surprised by this result. They had expected omega-3 fatty acids to be beneficial, but they had not expected them to be as beneficial as not smoking.

85% for non-smokers with high omega-3 intake.

71% for either…

- Smokers with high omega-3 intake, or…

- Non-smokers with low omega-3 intake.

Only 47% for smokers with low omega-3 intake.

In the words of the authors, “Smoking and omega-3 intake seem to be the most easily modified risk factors [for premature death]…Dietary choices that change the Omega-3 index may prolong life.”

For more details about this study, 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.

Omega 3 Supplementation And Heart Disease Risk

April 15, 2020April 14, 2020 by Dr. Steve Chaney

How Can You Reduce Your Risk Of Heart Disease?

I understand your confusion. One month the headlines say that omega 3 supplementation reduces the risk of heart disease. The next month headlines claim that omega 3 supplements are worthless. What is the truth about omega 3 supplementation and heart disease risk?

Let me start by sharing the two of the most recent studies on the topic. They are both very large, well designed studies. However, the reason I selected these two studies is that they approached the relationship between omega 3 supplementation and heart disease risk in very different ways but came to the same conclusion.

The first study (Y Hu et al, Journal of the American Heart Association, Volume 8, Issue 19, 1 October 2019) was a meta-analysis of 13 randomized controlled clinical studies looking at the relationship between omega 3 supplementation and heart disease risk.

The second study (Z-H Li et al, British Medical Journal, BMJ2020;368:m456) looked at the association between habitual omega 3 supplementation and heart disease risk.

Each of these studies had strengths and weaknesses, but they complemented each other. The weaknesses of one study were the strengths of the other study.

How Were The Studies Done?

Study #1: The 13 studies included in the meta-analysis had a total of 127,477 participants (mean age 64, 60% male, mostly overweight) who were given either an omega-3 supplement or a placebo.

40% of the participants had diabetes.

72% of the participants were on cholesterol lowering drugs and a variety of other medications.

Participants were followed for between 3 and 7.4 years (average follow-up period was 5 years).

The dose of omega 3s ranged between 376 and 4,000 mg/day.

The major strengths of this study were:

All 13 studies included in the meta-analysis were randomized, placebo controlled clinical trials.

The meta-analysis had a very large number of participants (nearly 130,000), so it was possible to accurately measure even small effects of omega 3 supplementation on heart disease risk.

The major weaknesses of this study were:

Most of the participants were already on multiple drugs that provided many of the same benefits as omega 3s, so it was impossible to assess the full effect of omega 3 supplementation on heart disease risk.

The duration of the clinical trials included in this meta-analysis was short compared to the decades required for heart disease to develop.

Most of the participants already had heart disease or were at high risk of developing heart disease. The people in these studies were not representative of the general population.

Study #2: The data for this study were obtained from the UK Biobank study which enrolled 427,678 participants (mean age 56, 45% male) from 22 medical centers across England, Scotland, and Wales. None of the participants had been diagnosed with heart disease or cancer at the time of enrollment.

At enrollment the participants filled out a detailed online questionnaire concerning their lifestyle, diet, diseases, medications, and supplement use. Among the questions was whether they habitually used fish oil supplements (Yes or No).

The participants were enrolled between 2006 and 2010 and followed for an average of 9 years.

31% of the participants were already taking omega 3 supplements on a regular basis at the time they enrolled in the study. This was the omega 3 supplementation group. The remaining 69% was the control group.

Only 10% of the participants were taking statin drugs or aspirin, probably because none of them had been diagnosed with heart disease.

Around 10% of the participants had high blood pressure and were taking blood pressure medications.

Most of the participants were slightly overweight but only 4% had diabetes.

The main strengths of this study were:

Very few of the participants were on medications. That means that medications did not interfere with the effect of omega 3 supplementation.

The participants were already using omega 3 supplements at the time of enrollment and were followed for an additional 9 years. That means that the duration of omega 3 supplement use was much longer than in the first study.

The participants were healthy and free of heart disease at the beginning of the study. That means that the results of this study focused more on prevention than on treatment. It also means the results are more applicable to the general population.

The main weakness of this study was:

It was an association study, which cannot prove cause and effect. In contrast, the first study was based on randomized, placebo controlled clinical trials, which can prove cause and effect.

In short, the weaknesses of the first study were strengths of the second study and vice-versa.

Omega 3 Supplementation And Heart Disease Risk

Study #1: The results from the meta-analysis of randomized, placebo-controlled clinical trials were that omega 3 supplementation:

Reduced heart attacks by 12%.

Reduced overall heart disease risk by 7%.

Reduced deaths from heart disease by 8%.

Because of the large number of participants included in the meta-analysis, all these reductions were highly significant.

The risk reduction was linearly related to the dose of omega-3s, but the study did not allow estimation of an optimal omega-3 dose.

The authors concluded: “Marine [fish oil] omega-3 supplementation lowers risk for heart attack, overall heart disease risk, and heart disease death…Risk reductions appear to be linearly related to marine omega-3 dose.”

Study #2: This study showed that regular use of omega-3 supplements:

Reduced deaths from all causes by 13%.

Reduced deaths from heart attacks by 20%.

Reduced deaths from all types of heart disease by 16%.

Because of the large number of participants, all these reductions were highly significant.

This study did not collect data on omega-3 dose, so the study did not allow estimation of an optimal omega-3 dose.

The authors concluded: “Habitual use of fish oil seems to be associated with a lower risk of all cause mortality and heart disease mortality…,supporting their use for the prevention of mortality from all causes and heart disease. Future studies are needed to examine the extent to which the dose of fish oil supplements influences the ability to achieve a clinically meaningful effect.”

While these studies did not provide information on the optimal omega 3 dose, a previous study concluded that an omega-3 intake of 835 mg/day or higher is needed to achieve clinically meaningful reductions in heart disease risk.

How Can You Reduce Your Risk Of Heart Disease?

These two studies support the value of omega 3 supplementation for reducing heart disease risk. However, while risk reductions were highly significant, the magnitude of risk reduction was relatively small. That means we should think of omega-3 supplementation as part of a holistic approach to reducing our health disease risk. It is just one piece of the puzzle.

With that in mind, here is what the American Heart Association recommends for reducing your risk of heart disease:

If you smoke, stop.

Choose good nutrition.

- Choose a diet that emphasizes vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, nontropical 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.

- If diet and physical activity don’t get those numbers under control, then medication may be the next step.

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.

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

The Bottom Line

Two major studies have recently been published on the relationship between omega 3 supplementation and heart disease. I felt it was important to evaluate these studies together because:

They are both very large, well designed studies.

They approached the relationship between omega 3 supplementation and heart disease risk in very different ways but came to the same conclusion.

They complemented each other. The weaknesses of one study were the strengths of the other study.

These studies showed that omega 3 supplementation:

Reduced heart attacks by 12-20%.

Reduced overall heart disease risk by 7%.

Reduced deaths from heart disease by 8-16%.

Reduced deaths from all causes by 13%

While these studies did not provide information on the optimal omega 3 dose, a previous study concluded that an omega-3 intake of 835 mg/day or higher is needed to achieve clinically meaningful reductions in heart disease risk.

For more details and the American Heart Association recommendations on what else you can do to reduce your risk of heart disease, 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 Reduce Heart Disease Risk

October 2, 2018 by Dr. Steve Chaney

Omega-3 Confusion

Author: Dr. Stephen Chaney

This article includes updates as of October 2, 2018. First, here is the earlier information.

Do omega-3s reduce heart disease risk?

The controversy around omega-3s and heart disease risk is part of the larger controversy around supplementation. It is omega-3 supplements that are controversial, not omega-3-rich fish. Of course, that completely ignores the fact that many omega-3-rich fish are contaminated with PCBs and/or heavy metals.

Why is omega-3 supplementation so controversial? The problem is that proponents of omega-3 supplementation often seize on a single study as “proof” that everyone should supplement with omega-3s. Opponents of omega-3 supplementation take the opposite approach. They pick studies showing that not everyone benefits from omega-3 supplementation as “proof” that nobody benefits. As usual, the truth is in between.

I have a section in my book, “Slaying The Food Myths,” called “None of Us Are Average.” In that section I point out that clinical studies report the average results of everyone in the study, but nobody in the study was average.

For example, let’s say the study reported that (on average) there was no heart health benefit from omega-3 supplementation. That is what makes the headlines. That is what opponents of omega-3 supplementation cite as “proof” omega-3 supplementation doesn’t work.

However, some of the people in the study may have benefited from omega-3 supplementation, while others did not. Thus, the important question is not “Does everyone benefit from omega-3 supplementation?” It is “Who benefits from omega-3 supplementation?” and “Why do the results vary so much from study to study?”

Omega-3 Confusion

I have a chapter in my book called “What Role Does Supplementation Play?” which helps put this omega-3 controversy into perspective. I created the graphic on the left to answer the question “Who needs supplementation?”

The concept is simple. Poor diet, increased need, genetic predisposition, and pre-existing disease all increase the likelihood that supplementation will be beneficial. However, the benefit will be most obvious in the center of the diagram where two or more of these factors overlap.

Let’s take this concept and apply it to studies of omega-3 fatty acids and heart disease risk. In particular, let’s use this concept to understand what I call “omega-3 confusion” – why some studies give negative results and others give positive results:

Poor Diet: Again, the concept is simple. You are most likely to see a benefit of omega-3 supplementation when the dietary intake of omega-3 fatty acids is low. Put another way, if the subjects in a study are already getting plenty of omega-3s from their diet, supplementing with omega-3s is unlikely to provide any benefit.

Until recently, dietary surveys were the standard method for assessing dietary omega-3 intake. However, dietary surveys can be inaccurate. The best of recent studies, measure the omega-3 levels in cellular membranes. The omega-3 levels at the beginning of the study reflect your diet. The omega-3 levels at the end of the study reflect how effective supplementation was at improving your omega-3 status. In short, this is the gold standard for omega-3 clinical studies. Subjects can lie about how many omega-3-rich foods they eat and whether they take their supplements, but the omega-3 levels in their cell membranes reveal the truth.

When you read the methods section, it turns out that most negative studies did not ask how much omega-3s their subjects were getting from their diet. Almost none of the negative studies measured omega-3 levels in cell membranes.

Increased Need: In terms of heart disease, we can think increased need as the presence of risk factors for heart disease such as:

Age
Obesity
Inactivity
Elevated cholesterol or triglycerides
Dietary factors like saturated fats and/or sugar and refined carbohydrates
Smoking

What does this mean in terms of clinical studies?

Studies in which most of the subjects have a poor diet, are over 65, and have multiple risk factors for heart disease are more likely to show a beneficial effect of omega-3s on heart disease risk.
Studies in which most of the subjects are young and healthy are unlikely to show a measurable benefit of omega-3s on heart disease risk. You would need to follow this population group 20, 30, or 40 years to demonstrate a benefit.

Genetic Predisposition: There is a lot we don’t know about genetic predisposition for heart disease. The only exception is family history. If you have a family history of early heart disease, you can be pretty certain you are at high risk for heart disease. As you might suspect:

Studies focused on populations with genetic predisposition to heart disease are more likely to show a benefit of omega-3 supplementation.
Studies that just look at the general population without consideration of genetic predisposition to heart disease are less likely to show a benefit of omega-3 supplementation.

Disease: Diseases like diabetes and high blood pressure increase heart disease risk. And, of course, pre-existing heart disease, especially a recent heart attack, dramatically increase the risk of a subsequent heart attack or stroke. Studies focusing on subjects with diabetes have been inconsistent. However, studies focusing on patients with pre-existing heart disease are more clear-cut:

Studies focused on populations with pre-existing heart disease and/or a recent heart attack are more likely to show a benefit of omega-3 supplementation.
Studies that just look at the general population without consideration of genetic predisposition to heart disease are less likely to show a benefit of omega-3 supplementation.

Interestingly, the situation is very similar with statin drugs. As I reported in a recent issue of “Health Tips From the Professor” on cholesterol lowering drugs, studies done with patients who had recently had a heart attack show a clear benefit of statin drugs, while studies with the general population show little or no benefit of statin drugs.

One More Factor: There is one more confounding factor that is somewhat unique to the omega-3-heart disease studies and, therefore, not included in the figure at the beginning of this section. Ethical considerations dictate that the placebo group in a double-blind, placebo controlled clinical study receive the “standard of care” for that disease. In the case of heart disease, the standard of care is 4-5 drugs which provide most of the same benefits as omega-3 fatty acids (although with many more side effects).

Thus, these studies are no longer asking whether omega-3s reduce heart disease risk. They are asking whether omega-3s have any additional benefits for heart disease patients already on 4-5 drugs. I have discussed this in more detail in a previous issue of “Health Tips From the Professor” on omega-3 and heart disease.

Why Are Omega-3 Studies Conflicting? In summary, the likelihood that clinical studies show a beneficial effect of omega-3 fatty acids on heart disease risk is highly dependent on study design and the population group included in the study. Many of the studies currently in the scientific literature are flawed in one way or another. Once you understand that, it is obvious why there are so many conflicting studies in the literature.

Unfortunately, meta-analyses that combine data from many studies are no better than the individual studies they include in the analysis. It is the old “Garbage in – garbage out” principle.

What Does An Ideal Study Look Like? In my opinion, an ideal study to evaluate the effect of omega-3s on heart disease risk should (at minimum):

Determine omega-3 levels in cellular membranes as a measure of omega-3 status (dietary intake of omega-3s plus their utilization by the body). The percentage of omega-3 fatty acids in cell membranes is referred to as Omega-3 Index. Based on previous studies (W.S. Harris et al, Atherosclerosis, 262: 51-54, 2017, most experts consider an Omega-3 Index of 4% to be low and an Omega-3 Index of 8% to be optimal.
Focus on a population group at high risk for heart disease or include enough subjects in the study so that you can determine the effect of omega-3s on high risk subgroups.
Measure cardiovascular outcomes (heart attack, stroke, cardiovascular deaths, etc.).
Perform the study long enough so that you can accumulate a significant number of cardiovascular events.
Include enough subjects for a statistically significant conclusion.

Do Omega-3s Reduce Heart Disease Risk?

Most of you have probably heard of the Framingham Heart Study. It was started in 1941 with a large group of residents of Framingham Massachusetts and surrounding areas. The data from this study over the years has shaped much of what we know about cardiovascular risk factors. The original participants have passed on, but the study has continued with their offspring, now in their 60s.

A recent study (W. H. Harris et al, Journal of Clinical Lipidology, doi: 10.1016/j.jacl.2018.02.010 ) with 2500 subjects in the Offspring Cohort of the Framingham Heart Study incorporates many of characteristics of a good omega-3 clinical study.

The average age of the subjects was 66. While none of the subjects enrolled in the study had been diagnosed with heart disease at the time the study began, this is a high-risk population. At this age a significant percentage of them would be expected to develop heart disease over the next few years.
The subjects did have other risk factors for heart disease. 13% of them had diabetes, 44% had high blood pressure, and 40% of them were on cholesterol medication. However, those risk factors were corrected for in the data analysis, so they did not influence the results.
The Omega-3 Index was measured in their red blood cell membranes at the beginning of the study.
The study was long enough (7.3 years) for cardiovascular disease to develop.

When they compared subjects with the highest Omega-3 Index (>6.8%) with those with the those with the lowest Omega-3 Index (<4.2%):

Death from all causes was reduced by 34%
Incident cardiovascular disease was reduced by 39% (Remember that none of the subjects had been diagnosed with heart disease at the beginning of the study. This terminology simply means that they received a new diagnosis of heart disease during the study.)
Cardiovascular events (primarily heart attacks) were reduced by 42%
Strokes were reduced by 55%.

There were two other interesting observations from the study:

There was no correlation between serum cholesterol levels and heart disease in this study.
The authors estimated that it would require an extra 1300 mg of omega-3s/day, either from a serving of salmon or from fish oil supplements, to bring the membrane Omega-3 Index from the lowest level in this study to an optimal level.

The authors cited three other recent studies performed in a similar manner that have come to essentially the same conclusion. These studies are not perfect. They are all association studies, so they do not prove cause and effect.

However, the authors concluded that Omega-3 Index should be measured routinely as a risk factor for heart disease and should be corrected if it is low.

The Bottom Line:

Perhaps there is nothing more controversial in nutrition today than omega-3 fatty acids and heart disease risk. It is so confusing. One day you are told they reduce heart disease risk. The next day you are told they are worthless. I have discussed the reasons for the conflicting results and the resulting omega-3 confusion in the article above.

I shared a recent study that escapes many of the pitfalls of previous studies because it measures the Omega-3 Index of red blood cells as an indication of omega-3 status.

When the study compared subjects with the highest Omega-3 Index (>6.8%) with those with the those with the lowest Omega-3 Index (<4.2%):

Death from all causes was reduced by 34%
Incident cardiovascular disease was reduced by 39% (Remember that none of the subjects had been diagnosed with heart disease at the beginning of the study. This terminology simply means that they received a new diagnosis of heart disease during the study.)
Cardiovascular events (primarily heart attacks) were reduced by 42%
Strokes were reduced by 55%.

There were two other interesting observations from the study:

There was no correlation between serum cholesterol levels and heart disease in this study.
The authors estimated that it would require an extra 1300 mg of omega-3s/day, either from a serving of salmon or from fish oil supplements, to bring the membrane Omega-3 Index from the lowest level in this study to an optimal level.

The authors concluded that Omega-3 Index should be measured routinely as a risk factor for heart disease and should be corrected if it is low.

Are Omega-3s Worthless?

Recommendations from the medical industry changes often. The following updates are in response to some of those changes concerning omega-3 and heart disease. These updates were added on October 2, 2018.

The internet is abuzz with headlines saying things such as “Omega-3 Supplements Don’t Protect Against Heart Disease” and “Forget Omega-3s”. Are those headlines true? Should we throw our omega-3 supplements in the trash?

If the recent headlines are true, it is confusing, to say the least. In the late 90s and early 2000s we were being told of clinical studies showing that omega-3s reduced the risk of heart attack and stroke. At that time the American Heart Association was recommending omega-3 supplements for patients at high risk of heart attack or stroke. What has changed?

It turns out that a lot has changed. The design of clinical studies has changed dramatically in the past 10-15 years. I have covered the changing omega-3 story in detail in my upcoming book “Slaying The Supplement Myths.” Let me just summarize a few key differences between the year 2000 and today.

The definition of “high risk of heart attack and stroke” has changed dramatically since 2000. Clinical studies today include subjects who have a much lower risk of heart attack and stroke. That makes it more difficult to see any benefits of omega-3s.
Most studies do not measure the omega-3 status of their subjects. That means they do not know whether their patients were omega-3 deficient at the beginning of the study. It also means they have no objective measure of how faithfully the subjects took their omega-3 capsules.
We are asking a totally different question today than we were in the year 2000. It is considered unethical to withhold “standard medical care” from the control group. In 2000 the standard of care was one or two heart medications and often did not include a statin. Back then we were asking “Do omega-3s reduce the risk of heart attack and stroke?” Today, the standard of care is 3-5 heart medications, each of which provides some of the same benefits as omega-3s. Today we are asking the question “Do omega-3s provide any additional benefit for people who are already taking 3-5 heart medications?”

Let me start by analyzing a recent study that illustrates these points perfectly.

How Was The Study Done?

On the surface the study appeared to be a well-designed study. The study (The ASCEND Study Collaborative Group, New England Journal Of Medicine, DOI: 10.1056/NEJMoa1804989, 2018 ) was conducted by scientists from the University of Oxford. They used a national diabetes registry and contacted general practitioners from all over England to identify 15,480 patients who had diabetes, but no evidence of heart disease and were willing to participate in the study. Participants were at least 40 (average age 63) and 60% male.

The participants were mailed a six month’s supply of capsules containing either 1 gram of omega-3s or olive oil as a placebo. Each 6 months the participants were mailed a questionnaire to report on whether they took the capsule daily and whether they had any adverse side effects. If they returned the questionnaire, they were given another 6 month’s supply of omega-3s or placebo. The patients were followed for an average of 7.4 years and “adverse vascular events” (simple definition: non-fatal and fatal heart attack or stroke) were recorded.

Omega-3 and Heart Disease?

The authors of the study reported:

Omega-3 supplementation had no significant effect on either serious vascular events or death from any cause.

The authors concluded “These findings, together with results of earlier randomized trials involving patients with and without diabetes, do not support the current recommendations for routine dietary supplementation with omega-3 fatty acids to prevent vascular events.”

On the surface, this appears to be a strong study and the results were conclusive. What could go wrong? The answer is “Plenty.”

What Are The Weaknesses Of The Study?

The study contains multiple weaknesses that have been ignored by the medical community and the press.

Omega-3 Supplements Reduced Vascular Deaths In This Study. To begin with, the study showed that omega-3 supplementation reduced vascular deaths (simple definition: fatal heart attacks and stroke) by 18%. That observation was reported as a single sentence in the Results section of the paper but did not appear in either the Discussion or Abstract. It was also not reported in any of the media reports telling you that omega-3s are worthless. Perhaps it did not match the preconceived beliefs of the authors.

This Study Was Not Really Looking At High Risk Patients. The studies in the late 90’s and early 2000’s showing a significant effect of omega-3s on heart attack risk were done with truly high-risk patients. For example, the best of these studies looked at the effect of omega-3 supplementation in patients who had suffered a heart attack in the past 6 months. Those patients were at high risk of a second heart attack in the next 6-12 months. They were in imminent danger.

This study looked at patients with diabetes. They have a 2 to 3-fold risk of heart attack or stroke over the next decade. That’s a big difference. In addition, this study only looked at patients with diabetes AND no evidence of heart disease. Their risk of heart attack and stroke is substantially less. In fact, if you look at the data in the study, 83% of the participants in their study were at low to moderate risk of heart disease. Only 17% were at high risk.

To put that into perspective, it has only been possible to prove the effectiveness of statins when they are tested in patients who have already suffered a heart attack. In low risk populations, their benefit is almost negligible. You will find details about those studies in my new book “Slaying The Supplement Myths.”

If you can’t prove statins are effective in low risk populations, why would you expect to be able to show omega-3s are effective in low risk populations.

The Subjects Were Already Getting Near Optimum Amounts of Omega-3s From Their Diet. The study analyzed the omega-3 index (a measure of omega-3 status) from a randomly selected subset of participants at the beginning and end of the study. They reported that the omega-3 index in their study participants increased from 7.1% at the beginning to 9.1% at the end, a 32% increase. They considered that to be a good thing because it showed that their participants were taking the omega-3 supplements faithfully.

However, let’s put that into perspective. An omega-3 index of 4% is associated with a high risk of heart disease. An omega-3 index of 8% is associated with a low risk of heart disease. It is considered optimum. With an omega-3 index of 7.1% at the beginning of the study, the subjects already had near optimum omega-3 status before the study even began.

If the subjects were already at near optimum omega-3 status, why would you expect additional omega-3 supplementation to be beneficial?

The Subjects Were On 3-5 Heart Medications. To discover this, you had to dig a little. Something only a science-wonk like me is willing to do. The Results section reported that 35% of the subjects were taking aspirin and 75% were on a statin. You have to go to the Supplementary Data online to discover that most of the subjects were on 3-5 heart medications in addition to 1 or 2 medications for diabetes. That is somewhat curious because nobody in the study had any detectable cardiovascular disease.

To understand the significance of this observation, we look at what the drugs do. Aspirin prevents blood clot formation in our arteries, which is one of the main benefits of omega-3s. For reasons nobody understands, statins decrease inflammation, which is another major benefit of omega-3s. Most of the subjects were also taking a medicine to decrease blood pressure, another major benefit of omega-3s.

If subjects are already on 3-5 heart medications that duplicate the benefits of omega-3s, why would you expect omega-3 supplementation to be beneficial?

As I said before, we are now asking a totally different question than we were in the studies performed in the late 90s and early 2000s. Back then we were asking whether omega-3s reduced the risk of heart disease. Today we are asking whether omega-3s have any additional benefits for someone who is already on 3-5 heart medications. That question may be of interest to your doctors, but it is probably not the question most of you are interested in.

Even worse, every one of those drugs has documented side effects. For example, the same group that published this paper also examined the role of aspirin in reducing heart attacks in the same patient population and concluded that the befits of aspirin were “largely counterbalanced by the bleeding hazard [caused by aspirin use],” (The ASCEND Study Collaborative Group, New England Journal Of Medicine, DOI: 10.1056/NEJMoa1804988, 2018). In contrast, they found no side effects in the group receiving 1 gram/day of omega-3s.

Garbage In Again, Garbage Out Again

Two recent meta-analyses (T Aung et al, JAMA Cardiology 3: 225-234, 2018 and Cochrane Database of Systematic Reviews ) have analyzed all the recent placebo-controlled studies and have concluded that omega-3s are of little or no use for reducing heart disease risk. However, those meta-analyses both suffered from what, in the computer programming world, is called “Garbage in. Garbage out.”

The meta-analyses included the studies from the late 90s and early 2000s, but the positive data from those studies was swamped out by all the recent negative studies, most of which suffered from the same flaws as the study I reviewed above. This is the “Achilles’ Heel” of meta-analysis. If they include flawed studies in their analysis, their conclusions will also be flawed. What the recent studies do tell us is that omega-3s are of little additional benefit if you are already taking multiple heart medications.

Don’t Throw The Baby Out With The Bathwater

The next time you visit your doctor you are likely to be told: “The evidence is in. We know that omega-3s don’t reduce the risk of heart attack.” Now you know the truth. What we can definitively conclude is that omega-3s offer little additional benefit if you are already taking multiple heart medications. As I said before, that question may be of interest to your doctor but is probably not the question you had in mind.

Unfortunately, because of the way clinical studies of omega-3 supplementation and heart disease risk are currently conducted, we may never have a definitive answer to whether omega-3s reduce heart disease risk for those of us who aren’t taking heart medications.

However, even if there is some controversy about omega-3s and heart disease risk, there are multiple other reasons for making sure that your omega-3 status is optimum. For example:

We know that omega-3s reduce triglycerides. This is non-controversial.
There is excellent evidence that omega-3s improve arterial health and reduce blood pressure.
There is good evidence that omega-3s reduce inflammation.

If they also reduce heart disease risk, consider that to be a side benefit.

The Bottom Line

A recent study has reported that that omega-3s do not reduce the risk of heart attack and stroke. However, the study suffered from multiple flaws.

Omega-3s reduced the risk of cardiovascular deaths in the study by 18%. That never got reported by the media.

The study was looking at subjects at relatively low risk of heart disease.

If you can’t even prove statins are effective in low risk populations, why would you expect to be able to show omega-3s are effective in low risk populations.

The subjects had near optimum omega-3 status before the study even began.

If the subjects were already at near optimum omega-3 status, why would you expect additional omega-3 supplementation to be beneficial?

The subjects were on 3-5 heart medications that provided many of the same benefits as omega-3s, but with side effects.

If subjects are already on 3-5 heart medications that duplicate the benefits of omega-3s, why would you expect omega-3 supplementation to be beneficial?

Two recent meta-analyses also concluded that omega-3s do not reduce the risk of heart disease. However, most of the studies in those meta-analyses suffered from the same flaws as the study I reviewed in this article. The meta-analyses are an excellent example of what computer programmers refer to as “Garbage in. Garbage out.”

The next time you visit your doctor you are likely to be told: “The evidence is in. We know that omega-3s don’t reduce the risk of heart attack.” Now you know the truth. What we can definitively conclude is that omega-3s offer little additional benefit if you are already taking multiple heart medications. That question may be of interest to your doctor, but that is probably not the question you had in mind.

Unfortunately, because of the way that clinical studies of omega-3 supplementation and heart disease risk are currently conducted, we may never have a definitive answer to whether omega-3s reduce heart disease risk for those of us who aren’t taking heart medications.

However, even if there is some controversy about omega-3s and heart disease risk, there are multiple other reasons for making sure that your omega-3 status is optimum. For example:

We know that omega-3s reduce triglycerides. This is non-controversial.
There is excellent evidence that omega-3s improve arterial health and reduce blood pressure.
There is good evidence that omega-3s reduce inflammation.

If they also reduce heart disease risk, consider that to be a side benefit.

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.