Omega-3 Supplements Are Safe

Why Do Clinical Studies Disagree? 

Author: Dr. Stephen Chaney 

Pendulum
Pendulum

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?

clinical studyScientists 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

Omega-3s And Heart DiseaseThe 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?

Question MarkRelative 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?

Confusion Clinical StudiesAs 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.

Doctor With Patient#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).

Heart Disease Study#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?

ConfusionScientists 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.

_____________________________________________________________________________

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

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

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

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

_______________________________________________________________________

About The Author 

Dr. Chaney has a BS in Chemistry from Duke University and a PhD in Biochemistry from UCLA. He is Professor Emeritus from the University of North Carolina where he taught biochemistry and nutrition to medical and dental students for 40 years.

Dr. Chaney won numerous teaching awards at UNC, including the Academy of Educators “Excellence in Teaching Lifetime Achievement Award”.

Dr Chaney also ran an active cancer research program at UNC and published over 100 scientific articles and reviews in peer-reviewed scientific journals. In addition, he authored two chapters on nutrition in one of the leading biochemistry text books for medical students.

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

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

Are Omega-3 Supplements Safe?

The Flaws And Blind Spots In This Study

Author: Dr. Stephen Chaney

Pendulum
Pendulum

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 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?

clinical studyThe 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 1st, 2006 and December 31st, 2010. Participants were followed from entry into the program until March 31st 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?

omega-3 fish oil supplementHere 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 thumbs upsupplementation:

  • 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

flawsFlaws: 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 Skepticignored 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 thatprofessor owl 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).

Confusion Clinical StudiesAs 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.

 ______________________________________________________________________________

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

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

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

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

 _______________________________________________________________________

About The Author 

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

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

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

Does EPA Reduce Migraine Frequency?

What Causes Migraines And The Role Of Omega-3s In Prevention

Author: Dr. Stephen Chaney

MigraineMigraines can be debilitating. And they affect millions of Americans. According to a recent survey 17.1% of women and 5.6% of men in the United States suffer migraine symptoms.

Symptoms range from frequent headaches to visual disturbances, nausea and vomiting, extreme light and sound sensitivity, brain fog, and debilitating pain. Sometimes all a migraine sufferer can do is retreat to a dark, quiet room and wait out the symptoms. This makes it virtually impossible to work, socialize, and interact with family.

For example, work absenteeism due to migraines is thought to cost US businesses up to $13 billion dollars annually. And, of course, there is no way to estimate the psychological cost of lost interactions with family and friends. And people who experience frequent migraines are more likely to suffer from depression, anxiety, and sleep disorders.

Medications can provide some relief from migraine symptoms, but they all have side effects. Various natural approaches for migraine relief have been proposed, but none of them are proven.

What Causes Migraines And The Role Of Omega-3s In Prevention

MigrainesOur understanding of migraines is complicated by the fact there appear to be multiple causes of migraines. It’s almost as if what we call “migraines” are really a variety of diseases with different causes but similar symptoms.

Migraines can be triggered by:

  • Hormonal fluctuations.
  • Weather changes.
  • Foods
    • The top 3 food triggers of migraines are caffeine, red wine, and chocolate.
    • Other common food triggers are artificial sweeteners, foods containing MSG, cured meats, aged cheeses, pickled and fermented foods, frozen foods, and salty foods.
  • Stress
  • Lack of sleep.
  • Certain drugs.
  • Missed meals.

Migraine triggers vary from person to person. And multiple neurophysiological pathways have been proposed to explain how each of these triggers progresses to a full-blown migraine.

To simplify a very complex subject, there are three main factors that influence each of these proposed pathways:

  • Susceptibility to migraines clearly runs in families.
  • 75% of migraine sufferers are women.
  • Inflammation.

Because inflammation plays a strong role in progression and severity of migraines, there has been a strong interest in the use of long-chain omega-3s like EPA and DHA as nutraceuticals to reduce the frequency and severity of migraines.

However, previous studies have had mixed results. Some have suggested that omega-3s reduce the risk of migraines while others have come up empty.

The authors of the current study (H-F Wang, et al, Brain, Behavior, and Immunity 118, 459-467, 2024) postulated that some previous studies failed to find a benefit of omega-3 supplementation because they were too short in duration, used a mixture of omega-3s, or were poorly designed.

They noted that high dose EPA alone had proven to be effective in reducing the risk of heart disease and depression. So, they performed a 12-week randomized, double-blind, placebo-controlled clinical trial with migraine sufferers using 1.8 grams of EPA per day.

How Was This Study Done?

clinical studyThis was a double-blind, placebo-controlled clinical trial, the gold standard for clinical studies. The investigators recruited 70 patients (15 men and 55 women) with episodic migraines (defined as migraines with or without aura occurring fewer than 15 days per month) from the neurology clinic of Kuang Tien General Hospital in Taiwan. The average age of the patients was 39 years old.

The subjects were randomly assigned to use either 1.8 gm/day of EPA or a soybean oil placebo for 12 weeks. Both were formulated with an orange flavoring to hide the taste difference. Neither the patients nor the physicians conducting the study knew who got the EPA and who got the placebo.

The patients filled out an extensive questionnaire about their migraines and related issues at entry into the study and at the end of 12 weeks. They were also asked to maintain headache diaries for at least 4 weeks prior to the study and for every 4 weeks of the 12-week study. They received training from the study coordinator on how to fill out the diaries and were encouraged to contact the coordinator if they had any questions about how to accurately fill out the diary.

The primary outcome of the study was the decrease in migraine frequency from baseline to 12 weeks. The study also assessed changes in:

  • Headache severity.
  • The need to use headache medicines.
  • Migraine-specific disability (The extent to which migraines resulted in disability).
  • Migraine-specific quality of life index (The extent to which migraines affected the quality of life).
  • Anxiety and depression (These are often side effects of chronic migraines).

While some of those outcomes appear to be overlapping, they are all well-established assessments used in migraine research. The questionnaire the doctors used was designed to provide a numerical rating for each of these outcomes.

Does EPA Reduce Migraine Frequency?

omega-3 fish oil supplementAs expected, there were no significant changes in the placebo group. But in the group taking 1.8 gm/day of EPA:

  • Migraine frequency decreased by 60%.
  • Frequency that headache medication was needed decreased by 45%.
  • Headache severity decreased by 14%.
  • Sleep quality increased by 17%, but that increase was not statistically significant.
  • Migraine-related disability decreased by 73%.
  • Migraine-related quality of life improved by 31%.
  • Anxiety and depression decreased by 53%.

These differences were statistically significant for the women in the study, but not for men – probably because of the small number of men in the study.

The study also assessed side effects from EPA supplementation in this group. Side effects were minimal and were not different from the placebo group.

The authors concluded, “High-dose EPA significantly reduced migraine frequency and severity. Improved psychological symptoms and quality of life in migraine patients, and showed no adverse events [effects], suggesting its potential for prophylactic use for migraine patients.”

They went on to say, “The results of this study may not only serve as a valuable reference for future large-scale randomized clinical trials to investigate the optimal dosing and components of omega-3 fatty acids for migraine prevention but also underscore the need for replication of these findings in adequately powered and controlled studies.”

In other words, this study needs to be confirmed by additional studies. And future studies need to determine the optimal dose of EPA and the optimal ratio of EPA to DHA.

What This Study Means For Us And For You

Question MarkThe topic of omega-3s and migraines is of special significance for us. About 40 years ago my wife and I started taking a high purity omega-3 supplement containing both EPA and DHA to control inflammation. We didn’t have noticeable inflammation at the time, but we both had parents who suffered from rheumatoid arthritis and wished to avoid their suffering later in life.

In just a few weeks the migraines my wife had been experiencing for years disappeared. That piqued my interest, so I searched the literature and found several studies showing that omega-3 fatty acids reduce migraine symptoms. I have followed the twists and turns of omega-3 – migraine research ever since, which is how I came across this study.

As for our original purpose in taking an omega-3 supplement, all I can say is that we are now in our 80s, and neither of us suffer from the rheumatoid arthritis that plagued our parents.

And for my wife the disappearance of her migraines was an unexpected side benefit.

This study is a strong validation of the effect of omega-3s on reducing migraine symptoms. However, it is not the end of the story. As the authors said:

  • It needs to be confirmed by larger, well controlled studies.
  • The optimal dose of omega-3s needs to be determined.
  • The optimal ratio of EPA to DHA and possibly other long chain omega-3s needs to be determined.

This study used 1.8 grams/day of pure EPA. My wife takes 3 grams of EPA and 2 grams of DHA each day. But we don’t know whether she would experience the same benefit from a lower dose or whether that is the optimal ratio of EPA to DHA. We do know that EPA and DHA have different health benefits, so we plan to continue taking a supplement that contains both.

And finally, as I said above, it is almost as if what we call migraines are really a cluster of diseases with similar symptoms. There are multiple migraine triggers and multiple proposed explanations of how these triggers lead to full-blown migraines.

So, we shouldn’t think of omega-3s as a magic bullet. Rather, we should think of them as one of many approaches that may provide you with some migraine relief.

The Bottom Line

A recent double-blind, placebo controlled clinical study with migraine sufferers reported that when they were given 1.8 gm/day of EPA for 12 weeks:

  • Migraine frequency decreased by 60%.
  • Frequency that headache medication was needed decreased by 45%.
  • Headache severity decreased by 14%.
  • Migraine-related disability decreased by 73%.
  • Migraine-related quality of life improved by 31%.
  • Anxiety and depression decreased by 53%.

The authors concluded, “High-dose EPA significantly reduced migraine frequency and severity. Improved psychological symptoms and quality of life in migraine patients, and showed no adverse events [effects], suggesting its potential for prophylactic use for migraine patients.”

They went on to say, “The results of this study may not only serve as a valuable reference for future large-scale randomized clinical trials to investigate the optimal dosing and components of omega-3 fatty acids for migraine prevention but also underscore the need for replication of these findings in adequately powered and controlled studies.”

In other words, this study needs to be confirmed by additional studies. And future studies need to determine the optimal dose of EPA and the optimal ratio of EPA to DHA.

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.

 ______________________________________________________________________________

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

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

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

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

____________________________________________________________________________

About The Author 

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

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

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

Do Omega-3s Reduce Osteoarthritis Pain?

How Do Rheumatoid And Osteoarthritis Differ?

Author: Dr. Stephen Chaney 

knee painThis week I am concluding my series on recent omega-3 advances by reviewing a meta-analysis that asks whether omega-3s are beneficial for people with osteoarthritis.

This is an important question because osteoarthritis affects around 32.5 million adults in the United States, and that number is increasing each year as our population ages. Osteoarthritis causes pain and disabilities that can significantly affect quality of life.

And the costs are high. Health care costs due to osteoporosis are around $140 billion/year. And when you include lost workdays, the annual cost is around $468 billion.

There are several medications for reducing symptoms of osteoarthritis. But they each have side effects and some patients cannot tolerate them. Joint replacement surgery is the final resort. But the recovery period is long, and the surgery isn’t always effective. For both reasons many patients with osteoarthritis are looking for natural solutions.

Most of the research on omega-3s and arthritis has been done with patients who have rheumatoid arthritis. Omega-3 supplements have been shown to reduce the pain, swelling of the joints, and inflammation associated with rheumatoid arthritis for many people with the disease.

Based on several dose-response studies, the NIH says the optimal dose is around 2.7 gm/day of EPA + DHA but cautions not to go above 3 gm/day without your doctor’s OK.

The evidence is less clear for omega-3s and osteoarthritis. Some studies suggest that EPA + DHA reduce the pain and inflammation associated with osteoarthritis. But other studies have come up empty. There is no consensus as to whether omega-3s are beneficial for people with osteoarthritis.

When there is disagreement between individual studies, a meta-analysis of the studies is often helpful. By pooling the data from multiple studies, a meta-analysis can smooth out some of the differences between the studies and accumulate enough data points to discover effects that would not have been statistically significant with the smaller data sets from individual studies.

With that in mind, the authors of this manuscript (W Den et al, Journal of Orthopaedic Surgery and Research, 18: 381, 3023) performed a meta-analysis on the data obtained from 9 double-blind, placebo-controlled studies looking at the effect of omega-3s versus a placebo on both pain and joint mobility in osteoarthritis patients.

How Do Rheumatoid And Osteoarthritis Differ?

While the causes of rheumatoid arthritis and osteoarthritis are very different, there are some underlying similarities between the two diseases that suggest both might benefit from omega-3 supplementation.

Rheumatoid Arthritis: Rheumatoid arthritis is thought to be an autoimmune disease, which means that our immune system attacks our cells rather than foreign invaders. It results in chronic inflammation that attacks our joints and can affect other tissues in our body.

It initially affects the lining of our joints which can result in painful, swollen joints. As the disease progresses it can also lead to bone erosion and joint deformity.

Osteoarthritis:Osteoarthritis is generally thought of as a “wear and tear” disease. It is associated with sports injuries and accidents. It is also associated with stress to particular joints due to repeated motions associated with either sports or a job. Obesity also increases wear and tear of the joints because it increases the load on the joints.

The wear and tear causes the cartilage that cushions the junction between bones to deteriorate. Eventually, the cartilage deteriorates to the extent that bone is grinding against bone, which can lead to bone loss and deformities.

Eventually, this results in an inflammation of the joint lining which causes pain and accelerates bone loss. It also causes deterioration of the connective tissue which holds bones together and connects them to muscle.

What Do These Diseases Have In Common? Inflammation is the common factor associated with both rheumatoid and osteoarthritis, and many studies suggest that omega-3s reduce inflammation. In the simplistic description of the two diseases I shared above, it sounds like inflammation occurs much earlier in the disease process for rheumatoid arthritis than for osteoarthritis. This might suggest that omega-3s could be more effective at reducing the symptoms and progression of rheumatoid arthritis than of osteoarthritis.

However, we know that the risk of developing osteoarthritis is increased by chronic inflammation caused by obesity, diseases like diabetes, and/or an inflammatory diet.

How Was This Study Done?

clinical studyThis study was a meta-analysis of 9 double-blind, placebo-controlled clinical studies looking at the effect of omega-3 fatty acids on the pain and loss of joint mobility associated with osteoarthritis. These studies were performed in countries from around the world and included a total of 2,070 participants.

The criteria for inclusion in the meta-analysis were:

1) The articles were written in English.

2) The studies had to be double-blind, placebo-controlled studies (The gold standard for clinical studies).

3) Patients with osteoarthritis were randomly assigned to an intervention group receiving omega-3 supplementation or a placebo group receiving olive oil or another plant oil.

4) The studies measured efficacy and safety outcomes including joint pain (efficacy), joint mobility (efficacy), and treatment-related adverse events (safety).

5) Patients in both the omega-3 and placebo groups were using medications to reduce osteoarthritis symptoms when they were enrolled in the study and were advised to continue with their prescribed medicines for the duration of the study.

The characteristics of the clinical studies included in this meta-analysis were:

  • Sample size (47-1221), Average = 230.
  • Mean age (55.9-68), Average = 63.
  • % men (13.8-45.1%), Average = 31%.
  • Omega-3 (EPA + DHA) dose (350 mg/day – 2,400 mg/day), Average = 1,085 mg/day.

Do Omega-3s Reduce Osteoarthritis Pain?

Question MarkWhen the data from all 9 studies were combined in a single meta-analysis, omega-3 (EPA + DHA) supplementation:

  • Reduced joint pain by 29% compared to the placebo.
  • Increased joint mobility by 21% compared to the placebo.
  • Was not associated with any adverse effects.

The authors concluded, “The results of the meta-analysis indicate that supplementation with omega-3 fatty acids is effective to relieve pain and improve joint function in patients with osteoarthritis, without increasing the risk of treatment-related adverse events. These findings support the use on omega-3 fatty acid supplementation as an alternative treatment for osteoarthritis.”

What Are The Strengths and Limitations Of This Study?

strengths and weaknessesStrengths:

  • All the studies included in this meta-analysis were randomized, double-blind, placebo-controlled studies (the gold standard for clinical trials).
  • All the individual studies that qualified for this meta-analysis found that omega-3 supplementation reduced joint pain and improved joint mobility. This improves confidence that the conclusions of the meta-analysis are correct. The meta-analysis simply improved the statistical significance of this conclusion by combining the data from the individual studies.

Limitations:

  • The biggest limitation was that the individual studies included in this meta-analysis were not performed under the guidelines of the “Fatty Acids and Outcomes Research Consortium” that I discussed in last week’s issue of “Health Tips From the Professor”.
    • The “Fatty Acids and Outcomes Research Consortium” guidelines harmonize the designs of individual studies, which strengthens the meta-analysis.
      • In contrast, the design of the individual studies within this meta-analysis was very different, which prevented the meta-analysis from being able to determine the optimal dose of omega-3 supplements and the minimum time required for omega-3 supplementation to significantly reduce the symptoms of osteoarthritis.
    • The “Fatty Acids and Outcomes Research Consortium” guidelines would have also required these studies to measure tissue levels of omega-3s (something called Omega-3 Index) at the beginning and end of each study. This was not done in any of these studies.
      • This is important because if a patient’s tissue levels of omega-3s at the beginning of the study were already in the optimal range, you would expect little additional benefit from supplementation for that patient.
  • All the individual studies were very small. This limits the ability of these studies to provide definitive conclusions. Unfortunately, this is probably unavoidable.
    • Double blind, placebo-controlled clinical studies are expensive. Only major pharmaceutical companies have the multi-million-dollar budgets required to conduct large double blind, placebo-controlled clinical studies that would provide more definitive evidence that omega-3 supplementation reduces the symptoms of osteoarthritis – and the follow-up studies that would determine the optimal dose of omega-3 supplements and the minimum time required to show an effect of omega-3 supplementation.
  • The patients in these studies were already taking medications to reduce their osteoarthritis symptoms prior to entering the study and were instructed to continue taking those medications during the study. This means that the studies were not asking whether omega-3s alone were effective at reducing osteoarthritis symptoms. They were asking whether omega-3 supplementation provided any additional benefits for people who were already taking medications to reduce symptoms.
    • Unfortunately, this is also probably unavoidable. Current guidelines consider it unethical to withhold the medical “standard of care” from any patient in a clinical trial.

What Does This Study Mean For You?

Questioning WomanThis study, while not definitive, strengthens the evidence that omega-3 supplements containing EPA + DHA may reduce joint pain and improve joint mobility for people with osteoarthritis. It also shows that the doses required to achieve these benefits are not associated with any significant side effects.

While large scale double blind, placebo-controlled clinical studies to confirm these conclusions would be nice, they are unlikely to occur for the reasons discussed above.

The investigators said, “[This study shows that] supplementation of omega-3 fatty acids is effective to relieve pain and improve joint function in patients with osteoarthritis…These findings support the use of omega-3 fatty acid supplementation as an alternative treatment for osteoarthritis.”

This might lead you to believe that omega-3 fatty acids can potentially replace medications for reducing osteoarthritis pain and loss of joint mobility. That may be true, but that is not what the study showed.

Patients in both the omega-3 and placebo group continued their prescribed medicines for osteoarthritis. In reality, the study only shows that omega-3s provide additional benefit for people already taking osteoarthritis medications. The effect of omega-3 supplements by themselves has not been tested and, as I discussed above, is not likely to be tested in the foreseeable future.

However, the use of omega-3 supplements may allow you to reduce or eliminate the medications you are on for osteoarthritis and may delay the need for joint replacement surgery. Of course, if you wish to reduce/eliminate your medications and/or delay joint replacement surgery, I recommend consulting with your doctor first.

Finally, this study provides no information on the optimal dose of omega-3s. Some studies suggest the dose of omega-3s needed to reduce osteoarthritis symptoms may be less than that required to reduce rheumatoid arthritis symptoms, but that evidence is weak.

In the absence of good dose response data, I recommend you aim for an omega-3 index of 8%. You will find a more detailed discussion of the Omega-3 Index and how to use it in last week’s “Health Tips From the Professor” article .

The Bottom Line

A recent meta-analysis looked at the effect of omega-3 supplementation on the pain and lack of joint mobility associated with osteoarthritis.

The study showed that omega-3 (EPA + DHA) supplementation:

  • Reduced joint pain by 29% compared to the placebo.
  • Increased joint mobility by 21% compared to the placebo.
  • Was not associated with any adverse effects.

The authors concluded, “The results of the meta-analysis indicate that supplementation with omega-3 fatty acids is effective to relieve pain and improve joint function in patients with osteoarthritis, without increasing the risk of treatment-related adverse events.”

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

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

_____________________________________________________________________________

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

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

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

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

_______________________________________________________________________

About The Author 

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

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

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

The Good News About Omega-3s And Stroke

How Do Omega-3s Affect The Two Types Of Stroke?

Author: Dr. Stephen Chaney 

strokeI am continuing my series on recent omega-3 breakthroughs. Last week I reviewed a study showing that the omega-3s EPA and DHA lowered blood pressure. Since high blood pressure is a major contributing factor to stroke risk, it only makes sense that EPA and DHA would also decrease the risk of strokes.

In last week’s article I mentioned that high blood pressure is called a silent killer. That is because the symptoms of high blood pressure are easy to ignore and often confused with other illnesses.

For many people the first indication they have a problem is when they have a stroke, which either kills them or forever impacts their quality of life. Let me share some statistics with you.

  • Every 40 seconds someone in the United States has a stroke. One in four adults over the age of 25 will have a stroke in their lifetime.
  • Every 4 minutes someone in the United States dies from a stroke. For many of them sudden death is the first indication they had a health problem.
  • The overall incidence of strokes has increased 60% in the last 20 years with most of that increase (65%) coming from younger adults (ages 20 to 45)
  • The cost of treatment, rehabilitation, and lost wages from stroke was $891 billion in 2020 and is projected to increase to $2.3 trillion in 2050.

Any way you look at it, the personal and financial costs of strokes are immense.

How Do Omega-3s Affect The Two Types Of Stroke?

There are two major kinds of stroke – ischemic stroke, which is caused by a thrombus (blood clot) in the carotid arteries leading to the brain, and hemorrhagic stroke, which is caused by bleeding from small blood vessels in the brain. Ischemic stroke accounts for around 85% of all strokes.

Ischemic strokes are caused by atherosclerosis, the buildup of fatty plaques in the walls of the carotid arteries, followed by the formation of a blood clot which lodges in the narrowed arteries. As you might expect, the prevention and treatment of ischemic strokes are similar to the prevention and treatment of heart attacks.

EPA and DHA have been shown to:

  • Reduce inflammation, which is associated with increased risk of heart disease and stroke.
  • Reduce blood pressure. High blood pressure damages the endothelial lining of blood vessels, which can lead to either build up of atherosclerotic plaque or rupturing of the blood vessels.
  • Reduce platelet aggregation and blood viscosity, which reduces the potential for inappropriate blood clots forming in the carotid arteries.

[When you cut yourself, you want a blood clot to form to stop the bleeding. That is an example of appropriate blood clot formation. However, when a blood clot forms within your arteries, it can prevent blood from reaching surrounding tissues. This is an example of inappropriate blood clot formation.]

  • Reduce the risk of atherosclerotic plaques rupturing. Rupturing of atherosclerotic plaques triggers blood clot formation, so this also decreases the risk of inappropriate blood clots forming in the carotid arteries.

Based on the known effects of EPA and DHA, it is not surprising that they would decrease the risk of ischemic strokes. But what about hemorrhagic strokes? Here the answer is not as clear cut.

  • In a previous clinical study 4 gm/day of purified EPA without DHA was associated with a slightly increased risk of bleeding events but did not increase the risk of hemorrhagic stroke.
  • High doses of pharmaceutical grade EPA have also been associated with a slightly increased risk of atrial fibrillation (Afib). In contrast, previous studies have shown that higher dietary intake of EPA + DHA are associated with a lower risk of Afib.

At present, we don’t know whether the increased risk of bleeding events and Afib are only seen at very high doses of omega-3s or are due to the use of pharmaceutical grade EPA without DHA and any of the other naturally occurring omega-3s.

However, this uncertainty has led some experts to warn that omega-3s may be a two-edge sword. They might increase the risk of hemorrhagic stroke while decreasing the risk of ischemic stroke. This uncertainty was part of the rationale for the study (JH O’Keefe et al, Stroke, 55: 50-58, 2024) I am describing today.

How Was This Study Done?

clinical studyThis study was a meta-analysis of 29 clinical studies looking at the effect of omega-3 fatty acids on the risk of both ischemic and hemorrhagic stroke. These studies were performed in 15 countries from around the world and included a total of 183,291 participants.

One major drawback of many meta-analyses is that each study in the meta-analysis is independently designed. Sometimes the studies are so different that it is difficult to fit them together in a coherent pattern.

A major strength of this meta-analysis is that all the studies were conducted within the “Fatty Acid and Outcome Research Consortium” which specifies a general protocol for the design of each study within that consortium.

For example, estimates of dietary omega-3 intake can be inaccurate and the uptake and utilization of both dietary and supplemental omega-3s vary from person to person. Because of that the Fatty Acid and Outcomes Research Consortium guideline specifies that studies rely on biomarkers of omega-3 levels in the body rather than the amount of omega-3s consumed.

The most frequently used biomarker was the percentage of omega-3s incorporated into the fatty portion of red blood cell membranes. Some studies used other biomarkers, such as the percentage of omega-3s incorporated into the fatty portion of plasma phospholipids or cholesterol-containing phospholipid particles (LDL and HDL for example).

In each case, the percentage of omega-3s is used to calculate something called an “Omega-3 Index”. Previous studies have shown that an Omega-3 Index of 4% or less correlates with a high risk of heart disease, and an Omega-3 Index of 8% or more correlates with a low risk of heart disease. In essence, this study correlated Omega-3 Index with the risk of stroke.

The Fatty Acids and Outcomes Research Consortium harmonized the studies included in this meta-analysis in several other ways, but the use of Omega-3 Index rather than omega-3 consumption was the most important.

Other key characteristics of the studies included in this meta-anaysis were:

  • The average age of participants was 65 years.
  • 82% of the participants were white and 53% were women.
  • The average length of follow-up was 14 years (range = 5-30 years).
  • 10,561 participants (5.8%) suffered a stroke during follow-up (78% ischemic, 11% hemorrhagic, and 11% unspecified).

The Good News About Omega-3s and Stroke 

good newsThe participants in these studies were divided into quintiles based on their Omega-3 Index. When those in the highest quintile (≥ 8%) were compared with those in the lowest quintile (≤ 4%):

  • Risk was reduced by 17% for total stroke and 18% for ischemic stroke. There was no effect on hemorrhagic stroke.

When the effect of individual components of the Omega-3 Index were analyzed:

  • For EPA + DHA risk was reduced by 17% for total stroke and 18% for ischemic stroke. There was no effect on hemorrhagic stroke.
  • For EPA risk was reduced by 17% for total stroke and 18% for ischemic stroke. There was no effect on hemorrhagic stroke. (You are probably starting to detect a pattern).
  • For DHA the results were only slightly different. Risk reduction was 12% for total stroke and 16% for ischemic stroke. There was no effect on hemorrhagic stroke.
  • For DPA, a minor component of the Omega-3 Index, there was no significant effect on total, ischemic, or hemorrhagic stroke.
  • There was a linear dose-response for the effect of EPA, DHA, and the two combined on the reduction in risk for both total and ischemic stroke.

When they looked at subgroups within the analysis, the results were the same for:

  • Age (<65 compared to >65).
  • Gender.
  • Studies that lasted less than 10 years and studies that lasted more than 10 years.
  • The presence of preexisting Afib.
  • The presence of preexisting cardiovascular disease.

The authors concluded, “In summary, this harmonized and pooled analysis of prospective studies showed that long-chain omega-3 levels were inversely associated with risk of total and ischemic stroke but were unrelated to risk of hemorrhagic stroke. Thus, higher dietary intake of DHA and EPA would be expected to lower risk of stroke.”

What Does This Study Mean For You?

Key Takeaways From This Study: The most important takeaway from this study is that reasonable amounts of EPA and DHA from either diet or supplementation are unlikely to increase your risk of hemorrhagic stroke (I will define reasonable below).

That is important to know because this and several other studies show that EPA and DHA decrease the risk of ischemic stroke, which accounts for around 85% of total strokes. This study shows you can reduce your risk of ischemic stroke without fearing that you will increase your risk of hemorrhagic stroke.

This study also reaffirms the importance of relying on Omega-3 Index rather than the dosage of omega-3s in a supplementation. Previous studies have shown there is significant individual variability in the uptake and utilization of dietary omega-3s.

Finally, this study shows you don’t need huge amounts of EPA and DHA to significantly decrease your risk of stroke and cardiovascular disease in general. An Omega-3 Index of ≥ 8% is sufficient to accomplish both.

How Much Omega-3s Do You Need? The authors of this manuscript are experts on the Omega-3 Index, and they estimated that:

  • To raise your Omega-3 Index from 5.4% (the median Omega-3 Index in these studies) to 8% would require about 1,000 mg/d of EPA + DHA.
  • To raise your Omega-3 Index from 3.5% (the lowest Omega-3 Index quintile in these studies) to 8% would require about 1,600 mg/d of EPA + DHA.

These intakes are well within the American Heart Association recommendations for reducing the risk of stroke and cardiovascular disease and are easily achievable from diet and supplementation.

But these estimates are based on averages, and, as I noted above, none of us are average. We differ in our ability to absorb and utilize omega-3s. So, I recommend relying on your Omega-3 Index rather than a dose of omega-3s that’s right for the average person but may not be right for you.

My recommendation would be to start with an Omega-3 test. If you are below 8%, start with the dosage of EPA + DHA the authors of today’s study recommended. Then retest in 6 months and adjust your dose based on the results of that test.

Question MarkHow Much Is Too Much? As I mentioned above, the dose response was linear for Omega-3 Index versus reduction in risk of total and ischemic strokes. So, the question becomes whether you might wish to increase your Omega-3 Index above 8% to achieve an even better reduction in stroke risk.

That is a very personal decision that only you can make but let me share some facts to help you make that decision.

  • As I mentioned above, a previous clinical trial showed an increased risk of bleeding events and Afib at a dosage of 4 gm/day of pure EPA. We don’t know whether that was because of the dose or the use of a formulation that contained only EPA without DHA and other naturally occurring long-chain omega-3s.
  • In that study the increase in bleeding events and Afib was observed in <5% of participants, which suggests that those side effects may be limited to certain high-risk individuals.
    • In this context, high risk might include individuals with preexisting Afib, individuals with a tendency towards excess bleeding, and patients on blood thinning medications.
    • However, only your physician knows all your risk factors. If you have health issues or are on medications, it is always a good idea to check with your physician before changing your omega-3 intake. And if you are considering high-dose omega-3 supplementation or exceeding an 8% Omega-3 Index, I strongly recommend that you consult with your physician first.

The Bottom Line

A recent study looked at the effect of omega-3 levels in red blood cells and other tissues (something called Omega-3 Index) on the risk of various types of stroke.

When individuals with an Omega-3 Index ≥ 8% were compared with those with an Omega-3 Index of ≤ 4%:

  • Risk was reduced by 17% for total stroke and 18% for ischemic stroke (stroke caused by blood clots in the carotid arteries). There was no effect on hemorrhagic stroke (stroke caused by bleeding from small blood vessels in the brain).

The authors concluded, “In summary, this harmonized and pooled analysis of prospective studies showed that long-chain omega-3 levels were inversely associated with risk of total and ischemic stroke but were unrelated to risk of hemorrhagic stroke. Thus, higher dietary intake of DHA and EPA would be expected to lower risk of stroke.”

This study represents an important breakthrough. There is good evidence that increased EPA + DHA from food and/or supplements reduces the risk of ischemic stroke. But some experts have cautioned it might also increase the risk of hemorrhagic stroke. This study puts that fear to rest.

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

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

_______________________________________________________________________________

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

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

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

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

About The Author 

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

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

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

 

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

What Does This Study Mean For You?

Author: Dr. Stephen Chaney

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

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

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

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

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

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

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

How Was This Study Done?

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

The studies included in this meta-analysis:

  • Included omega-3 intake from both diet (mackerel, salmon, trout, or tuna) and supplements (fish oil, algal oil, or purified omega-3 ethyl esters).
  • Were conducted in populations from Europe, North America, Australia and other Pacific islands, and Asia.
  • Included subjects with normal blood pressure as well as those with high blood pressure.
  • Ranged in length from 5 to 52 weeks (the average was 10 weeks).
  • Included approximately equal numbers of men and women.

The meta-analysis excluded studies that:

  • Lacked a placebo.
  • Lasted less than 4 weeks.
  • Included blood pressure medications.
  • Included individuals with preexisting cardiovascular events.

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

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

Fish Oil and Blood PressureWhen the investigators combined the data from all 71 studies:

  • The maximum reduction in both systolic and diastolic blood pressure was observed between 2g/d and 3 g/d.
  • The dose response was non-linear. Doses above 3 g/d offered no additional benefit.

When the investigators looked at subgroups within the studies:

  • Reduction in blood pressure was seen in both subjects with normal blood pressure and those with high blood pressure.
    • However, reduction in blood pressure and the dose response were different in the two groups.
      • In subjects with normal blood pressure the dose response was non-linear with the optimum reduction between 2 and 3 g/d.
      • In subjects with high blood pressure the reduction in blood pressure was greater and the dose response was linear. The authors recommended a dose ≤ 3 g/d EPA + DHA for people with high blood pressure.
  • Subjects with hyperlipidemia had a greater reduction in blood pressure than subjects with normal lipid levels, and the dose-response was linear.
  • Subjects over the age of 45 had a greater reduction in blood pressure than subjects under the age of 45, and the dose response was linear.
  • There were no significant differences between:
    • Diet versus supplementation.
    • Type of omega-3 supplement (natural fish oil versus purified ethyl ester).
    • Sex.

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

I should probably explain the reasoning behind this conclusion.

  • 79% of the studies included in this meta-analysis were performed with subjects who had normal blood pressure. This group had a non-linear reduction in blood pressure with an optimal reduction between 2 and 3 g/d EPA + DHA.
    • Because of its size this group exerted a major influence on the results, which explains why the average results for the entire group showed a non-linear reduction in blood pressure with an optimal reduction between 2 and 3 g/d EPA + DHA.
    • Subjects with normal blood pressure and normal lipid levels are at low risk of cardiovascular disease. The high-risk groups (high blood pressure, high cholesterol and/or triglyceride levels, and over 45) all had a linear dose response suggesting that doses above 3 g/d EPA + DHA may be optimal.

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

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

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

What Does This Study Mean For You?

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

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

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

  • For example, the European Food Safety Authority has said, “An intake of EPA and DHA of ~3 g/d is required to bring out the claimed hypotensive (blood pressure lowering) effect”.
  • The FDA has approved qualified health claims stating that consuming EPA and DHA in foods or dietary supplements may reduce the risk of hypertension (high blood pressure) and coronary heart disease but did not recommend a dose to achieve these results.
  • The American Heart Association has recommended ~ 1 g/d of EPA + DHA for patients with documented coronary heart disease and 2–4 g/day of EPA + DHA to lower triglycerides.
  • And the American Heart Association features this article on their website with the headline, “Consuming about 3 grams of omega-3 fatty acids a day may lower blood pressure.”

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

The Rest Of The Story

ProfessorThere are four additional points I would like to make:

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

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

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

  • This study and similar studies measure the health benefits of the long chain omega-3 fatty acids EPA and DHA. Short chain omega-3s from nuts, seeds, and plant oils are healthy, but their conversion to EPA and DHA is very inefficient.
  • Both the FDA and American Heart Association recommend that doses of EPA + DHA above 3 g/d should be taken under a physician’s supervision because high doses can cause bleeding problems.

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

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

The Bottom Line 

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

  • The study concluded that a dose of 2-3 mg/d of EPA + DHA was optimal for preventing a future increase in blood pressure and all its associated health consequences.
  • It also concluded that an EPA+ DHA dose ≥ 3g/d was optimal for lowering blood pressure in people who already have high blood pressure and/or other risk factors for heart disease.
  • Based on previous studies, I recommend optimizing your omega-3 index rather than relying on a dose of EPA + DHA that may not be right for you.

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

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

 ______________________________________________________________________________

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

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

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

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

About The Author 

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

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

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

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

Where Do We Go From Here? 

Author: Dr. Stephen Chaney 

Omega-3s And Heart DiseaseDespite 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?

clinical studyThe 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?

heart attacksWhen 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.good news

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? 

Questioning WomanI 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?

Where Do We Go From HereThe 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.

 ______________________________________________________________________________

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

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

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

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

_______________________________________________________________________

About The Author 

Dr. Chaney has a BS in Chemistry from Duke University and a PhD in Biochemistry from UCLA. He is Professor Emeritus from the University of North Carolina where he taught biochemistry and nutrition to medical and dental students for 40 years.  Dr. Chaney won numerous teaching awards at UNC, including the Academy of Educators “Excellence in Teaching Lifetime Achievement Award”.

Dr Chaney also ran an active cancer research program at UNC and published over 100 scientific articles and reviews in peer-reviewed scientific journals. In addition, he authored two chapters on nutrition in one of the leading biochemistry text books for medical students.

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

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

Do Omega-3s Reduce Cognitive Decline?

Should You Supplement With Omega-3s?

Author: Dr. Stephen Chaney 

Cognitive-DeclineDo omega-3s reduce cognitive decline, or is this another nutrition myth?

There is certainly good reason to believe that the long chain omega-3s EPA and DHA are good for brain health.

  • DHA is an essential part of the membrane that coats our neurons. As such, it is a major component of our brains and plays an important role in its structural integrity.
  • While EPA is not found in the brain it reduces inflammation and improves blood flow to the brain, both of which are important for brain health.

But the role of DHA and EPA in reducing cognitive decline remains controversial. Some studies strongly support their role in slowing cognitive decline while other studies find no effect.

So, the question remains, “Do omega-3s reduce cognitive decline or not?”

The study (B-Z Wei et al, American Journal of Clinical Nutrition, 117: 1096-1109, 2023) I will review today was designed to answer that question.

This study supports the hypothesis that omega-3s, especially DHA and EPA, reduce cognitive decline and Alzheimer’s disease. But it also raises several questions that need to be resolved by future studies.

Why Is The Effect Of Omega-3s On Cognitive Decline Controversial?

ArgumentWhy is it so difficult to come up with definitive answers about whether omega-3s reduce cognitive decline? It is probably because the relationship between omega-3s and brain health is complex. For example:

  • Because omega-3’s beneficial effects are widely publicized, many people are already consuming adequate amounts of omega-3s. A supplement study that does not measure the omega-3 status of participants at the beginning of the study and does not focus on participants with inadequate omega-3 status is doomed to failure.
  • Omega-3s may benefit older people more than younger people. A study that is not large enough to measure the effect of omega-3s on both groups is doomed to failure.
  • The APOE ɛ4 genotype is associated with an increased risk of cognitive decline and Alzheimer’s. Some studies suggest omega-3s are more beneficial for people with the APOE ɛ4 genotype, while other studies come to the opposite conclusion. This is a critical variable that needs to be resolved.
  • The ability of DHA to cross the blood-brain barrier and accumulate in our brain may be influenced by our genetics, especially our APOE ɛ4 status, and adequate levels of other nutrients, especially B vitamins. Unless studies are large enough to separate out these variables, they are doomed to failure. This study suggests accumulation of DHA in the brain is a critical variable that needs to be resolved.
  • Multiple studies suggest that higher doses of omega-3s are more effective at reducing cognitive decline than low doses of omega-3s. This study confirms that effect and identifies a threshold dose that is needed to provide measurable benefits. Studies providing supplemental omega-3s at doses below that threshold are likely to fail. And meta-analyses that combine low dose studies with high dose studies are also likely to come up empty.
  • Finally, people who take omega-3s for years are likely to benefit more than those who take omega-3s for just a few months. Again, this study confirms that effect, which means that studies involving short-term supplementation with omega-3s are likely to fail. And meta-analyses that combine short-term and long-term studies are likely to come up empty.

With so many potential pitfalls, it is easy to understand why many studies come up empty, and the effect of omega-3s on cognitive decline remains controversial.

How Was This Study Done?

clinical studyThis study consisted of two parts:

Part 1 used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The ADNI study is a multicenter study designed to develop clinical, imaging, genetic, and biochemical markers for early detection and tracking of Alzheimer’s Disease.

Participants undergo standardized neuroimaging, psychological assessments, in-person interviews for medical history, and cognitive evaluations on entry into the study and at the end of the study.

This study followed a cohort of 1135 participants (average age = 73, 46% females) without dementia at entry into the study for 6 years.

Omega-3 supplement use was determined based on a questionnaire at the beginning of the study. Participants who used omega-3 supplements for over a year were considered omega-3 users. They were further divided into medium-term users (1-9 years) and long-term users (>10 years).

Alzheimer’s Disease was diagnosed by neurologists based on brain scans, cognitive scores, and the ability to live independently.

Part 2 was a meta-analysis of 31 studies with 103,651 participants. The studies included in the meta-analysis all:

  • Measured the relationship of omega-3 intake with the risk of Alzheimer’s Disease, all-cause dementia, or cognitive decline.
  • Were cohort studies (studies that follow a group of people over time) or case control studies (studies that compare people who develop a disease with those who do not).
  • Provided risk estimates or data that could be used to calculate risk.
  • Were original publications, not reviews or meta-analyses.

Do Omega-3s Reduce Cognitive Decline?

omega 3 supplementsThe results from Part 1 (data from the ADNI study) were as follows:

  • Omega-3 supplement users had a 37% lower risk of developing Alzheimer’s Disease than non-users.
  • Long-term (>10 years) omega-3 supplement users fared even better. They had a 64% lower risk of developing Alzheimer’s Disease than non-users.
  • When they broke the results for long-term omega-3 supplement users into subgroups:
    • Males (67% risk reduction) benefitted more than females (50% risk reduction).
    • People over 65 (65% risk reduction) benefited more than those under 65 (22% risk reduction).
    • People with the APOE ɛ4 genotype (71% risk reduction) benefitted more than those who were APOE ɛ4 negative (55% risk reduction).

The results from Part 2 (data from the meta-analysis) were as follows:

  • Dietary omega-3 intake lowered the risk of cognitive decline by 9%.
    • People with the APOE ɛ4 genotype fared better (17% risk reduction).
    • Their data suggested that a threshold of 1 gm/day omega-3s was needed before significant risk reduction was seen.
  • Dietary DHA intake lowered the risk of dementia by 27% and Alzheimer’s Disease by 24%.
  • Each 100 mg/day increase in DHA and EPA was associated with a significant reduction in the risk of cognitive decline (8% for DHA and 9.9% for EPA).

The authors concluded that,

1) “Long-term omega-3 supplementation may reduce risk of Alzheimer’s Disease; and

2) Dietary omega-3 fatty acid intake, especially DHA, may lower risk of dementia or cognitive decline…

3) However, further investigation is needed to understand the gene environment interactions involved in…[these effects of omega-3 fatty acids].”

Should You Supplement With Omega-3s?

QuestionsThis study provides strong support for the hypothesis that omega-3 supplementation reduces the risk of cognitive decline, dementia, and Alzheimer’s Disease as we age. It also suggests that a dose of 1 gram/day may be needed to obtain a significant benefit.

However, it also highlights the difficulty in designing definitive experiments to test this hypothesis. This study shows that gender, age, genetics (especially the APOE ɛ4 genotype), type of omega-3s, dosage, and duration of supplementation all exert a significant influence on the effect of omega-3s on cognitive decline.

It is extremely difficult to design a study that optimizes all these variables, which almost guarantees that the effect of omega-3s on cognitive decline will remain controversial for the foreseeable future.

However, omega-3s lower blood pressure, lower triglycerides, reduce inflammation and are heart-healthy. And the threshold for all these effects is around 1 gram/day or more. If omega-3s also reduce cognitive decline, you can consider that a side-benefit.

The Bottom Line 

The role of omega-3s in reducing cognitive decline remains controversial. Some studies strongly support their role in slowing cognitive decline while other studies find no effect.

So, the question remains, “Do omega-3s reduce cognitive decline or not?”

A recent study was designed to answer that question. Among other things the study showed:

  • Omega-3 supplement users had a 37% lower risk of developing Alzheimer’s Disease than non-users.
  • Long-term (>10 years) omega-3 supplement users fared even better. They had a 64% lower risk of developing Alzheimer’s Disease than non-users.
  • Dietary DHA intake lowered the risk of dementia by 27% and Alzheimer’s Disease by 24%.
  • Each 100 mg/day increase in DHA and EPA was associated with a significant reduction in the risk of cognitive decline (8% for DHA and 9.9% for EPA).
  • The threshold for observing a significant effect of omega-3s on cognitive decline was around 1 gram/day.

This study provides strong support for the hypothesis that omega-3 supplementation reduces the risk of cognitive decline, dementia, and Alzheimer’s Disease as we age. It also suggests that a dose of 1 gram/day may be needed to obtain a significant benefit.

However, it also highlights the difficulty in designing definitive experiments to test this hypothesis. This study shows that gender, age, genetics (especially the APOE ɛ4 genotype), type of omega-3s, dosage, and duration of supplementation all exert a significant influence on the effect of omega-3s on cognitive decline.

It is extremely difficult to design a study that optimizes all these variables, which almost guarantees that the effect of omega-3s on cognitive decline will remain controversial for the foreseeable future.

However, omega-3s lower blood pressure, lower triglycerides, reduce inflammation and are heart-healthy. And the threshold for all these effects is around 1 gram/day or more. If omega-3s also reduce cognitive decline, you can consider that a side-benefit.

For more information on 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.

 ___________________________________________________________________________

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

 

 

Should Athletes Be Taking Omega-3s?

Can Omega-3s Protect Your Brain?

Author: Dr. Stephen Chaney 

Contact sports like football and soccer can be an athlete’s ticket to fame and fortune. That is a powerful motivator. But many elite athletes in contact sports pay a terrible price after their playing days are over.

Repeated head trauma can lead to a condition called Chronic Trauma Encephalopathy or CTE. In CTE, a protein called Tau forms clumps that spread through the brain, killing brain cells. Eventually, this can lead to irrational behavior and/or early-onset Alzheimer’s, which is, indeed, a terrible price to pay for their brief moment in the spotlight.

The NCAA is aware of the damaging effects of repeated head trauma and are experimenting with rule changes and improvements to protective head gear to reduce it. But, given the pressures of college teams to win at all costs, it will be impossible to completely eliminate head trauma from contact sports.

So, it is important to ask, “What else we can do?” Several studies have suggested that omega-3s may mitigate the damaging effect of repeated head trauma. For example:

  • The omega-3s DHA and EPA are metabolized to molecules called resolvins and protectins, which protect brain tissue from oxidative stress and help restore damaged brain tissue.
  • DHA and EPA also reduce the inflammation associated with brain injury, so the brain can heal faster.
  • DHA and EPA boost the level of a protein called BDNF in the brain. It helps trigger the production of new brain cells, which also aids in the recovery from brain injury.
  • Finally, some medical clinics have reported that high dose omega-3s help speed the recovery from severe head trauma.
  • This is concerning because omega-3s are largely missing from the diet of college athletes.

This raises the question, “Should athletes be taking omega-3s?”omega 3 supplements

The kinds of studies mentioned above suggest that DHA and EPA might help protect athletes from the damaging effects of repeated head trauma, but it is difficult to prove:

  • If a patient comes into a clinic with severe brain trauma, the symptoms are obvious. And if omega-3s speed recovery it will become apparent in weeks or months. This effect is easy to measure.
  • On the other hand, the effects of repeated, minor head trauma on a highly trained athlete are often not apparent until decades later. Therefore, any protective effects of omega-3s would also not become apparent for decades. Clinical studies don’t last that long.

Because of this, current research focuses on markers of brain damage such as neurofilament light chain or Nf-L. Nf-L is a neuronal protein that is released into the bloodstream by dying neurons. It is widely considered to be an early marker for neurodegenerative diseases such as those seen in former college football players. Previous studies have shown:

  • Nf-L blood levels increase during the season for NCAA-level college football players.
  • College football players have a very low omega-3 index, a measure of omega-3 status.
  • DHA supplementation reduces Nf-L levels in college football players.

With this in mind, the authors of this study (JL Heileson et al, Journal of the International Society of Sports Nutrition 18:65, 2021) looked at the effect of a high-dose, comprehensive omega-3 supplement on Nf-L levels in the blood of NCAA football players during the playing season.

How Was This Study Done?

clinical studyVolunteers from two geographically distinct NCAA football teams were recruited for this study. One team (n=31) was given a daily high-dose omega-3 supplement providing 2,000 mg of DHA, 560 mg of EPA, and 320 mg of DPA starting during pre-season (fall) practices and continuing through the entire season. Compliance with the supplement regimen was 93%.

Volunteers from the other team (n=35) received no supplements and served as a control.

Participants from both teams were advised which foods were high in omega-3s and were asked to limit servings to no more than 2 per week for the duration of the study.

Players were excluded from the study if they:

  • Were on long-term (>20 days) anti-inflammatory therapy.
  • Were using fish oil supplements.
  • Ate more than two servings of fish per week.
  • Were on medications to control blood pressure or blood lipid levels.

Blood samples were drawn 7 days before pre-season practice, at the end of pre-season practice, 3 times during the season, and at the end of the season (a total of 6 blood draws).

The blood samples were analyzed for Nf-L, a marker of brain injury, and Omega-3 Index, a measure of omega-3 status.

Should Athletes Be Taking Omega-3s?

As I stated above, compliance with the supplementation regimen was excellent (93%) and this was reflected in the blood levels of long-chain omega-3s. Between the first and last blood sample drawn:

  • DHA and EPA levels increased 2-fold.
  • DPA levels, on the other hand, decreased slightly.
    • This suggests that the beneficial effects of omega-3 supplementation were primarily due to DHA and EPA. I will discuss the implications of this below.
  • The omega-3 index increased from 4.3%, which is considered poor, to 7.4%, which is considered near optimal.

The effect of omega-3 supplementation on Nf-L levels was striking:

  • In the control team (no supplementation) Nf-L levels increased 1.5-fold during the pre-season practices and remained elevated throughout the regular season.
  • In the team receiving omega-3 supplementation there was no significant increase in Nf-L levels.

The authors of the study concluded, “These findings suggest a…neuroprotective effect of combined EPA+DPA+DHA omega-3 fatty acid supplementation in American-style football athletes.”

The authors went on to say, “Similar elevations of Nf-L have been reported with RHI [repeated head injuries] in other contact sport athletes. These data suggest that those other contact sports athletes may also benefit from omega-3 supplementation…”

So, let’s return to the original question, “Should athletes be taking omega-3s?” Here is my take on the study:

  • The conclusions of the authors are appropriately cautious. This study shows that omega-3 supplementation reduces an indicator of possible brain damage (Nf-L), but the actual symptoms of brain damage don’t appear for decades.
    • Therefore, this study suggests, but doesn’t prove, that omega-3 supplementation may reduce Chronic Trauma Encephalopathy (CTE) for athletes who competed in contact sports during their college years.
  • This study used an omega-3 supplement containing EPA, DHA, and DPA. It resulted in an increase in EPA and DHA levels, but not DPA levels. Thus, there is no evidence that the DPA portion of the supplement was needed. I recommend a supplement with a 4:1 ratio of DHA to EPA for brain health.
  • This study did not establish an optimal dose of omega-3s. Until more information is available, I would recommend around 2,000 mg of DHA and 500 mg of EPA for athletes in contact sports, but the optimal dose may be lower or higher.

Can Omega-3s Protect Your Brain?

If you are not a college athlete competing in contact sports (which would include most of us), you are probably wondering what this means for you. Here are my thoughts.

As Benjamin Franklin said, “An ounce of prevention is worth a pound of cure.”

  • You never know when you may suffer unexpected head trauma. It could be a car accident. It could be a fall. You might be playing a friendly game of softball and get hit in the head by a foul ball. You get the point.
  • And the best time to make sure you have enough omega-3s (specifically DHA + EPA) in your brain is before the trauma occurs.

But how much DHA + EPA is enough? This is where it gets confusing.

  • Recommendations range from 500 mg/day to 3,000 mg/day depending on whether the goal is to reduce death from heart disease, lower blood pressure, or lower triglycerides.
  • This study used 2,500 mg/day to reduce a marker of brain damage in college athletes, but we don’t know whether that is optimal.
  • Finally, these numbers are averages, and none of us are average. We all utilize omega-3s from supplements with different efficiencies.

My recommendation is to use the Omega-3 Index as a gauge. It tells us how much DHA + EPA we have actually accumulated in our tissues.

  • An Omega-3 Index of 8% is considered optimal for heart health, and this study suggests it might be optimal for brain health as well.
  • So, my recommendation is to get your Omega-3 Index measured at 6-month intervals until you have determined the amount of supplemental DHA + EPA you need to attain and maintain an 8% Omega-3 Index.
  • Based on this study, I would recommend a high-purity supplement with an ~4:1 ratio of DHA to EPA if your primary goal is brain health. But other studies suggest that an EPA to DHA ratio of 3:2 may be optimal for heart health.

In short:

  • While the evidence is not definitive, this study suggests that it might be prudent to have accumulated enough DHA and EPA in your neural tissue to help reduce the complications of unexpected brain trauma.
  • This study also suggests that you may wish to aim for an Omega-3 Index of 8%.
    • An Omega-3 Index of 8% likely has side benefits. There is also evidence that it may reduce the rate of cognitive decline as you age, help protect your heart, and reduce inflammation.
  • The ratio of DHA to EPA in the supplement you choose may be different for brain health and heart health. If you are equally interested in brain and heart health, just be sure your supplement provides both DHA and EPA.

The Bottom Line 

Repeated head injuries are a major concern for NCAA football players and college athletes in other contact sports. That’s because repeated head injuries during their playing years are associated with a degenerative brain condition called Chronic Trauma Encephalopathy or CTE, which can lead to irrational behavior and/or early-onset Alzheimer’s.

A recent study looked at the effect of a high-dose, comprehensive omega-3 supplement on Nf-L, a marker of brain injury, in NCAA football players during the playing season. Two teams were selected.

  • In the team receiving no omega-3s, Nf-L increased 1.5-fold during preseason practice and remained elevated throughout the playing season.
  • In the team receiving omega-3 supplementation there was no significant increase in Nf-L levels.

The authors of the study concluded, “These findings suggest a…neuroprotective effect of… omega-3 fatty acid supplementation in American-style football athletes.”

The authors went on to say, “Similar elevations of Nf-L have been reported with RHI [repeated head injuries] in other contact sport athletes. These data suggest that those other contact sports athletes may also benefit from omega-3 supplementation…”

For more information on this study and what it means for all of us who are not college athletes, read the article above.

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

 ____________________________________________________________________________

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

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

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

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

 

 

Can You Slow The Aging Process?

A Holistic Approach To Living Healthy Longer

Author: Dr. Stephen Chaney 

Fountain Of YouthEver since Ponce de Leon’s famed 1513 expedition, people have been searching for the proverbial “Fountain of Youth”.

There have been hucksters selling pills and potions to reverse the aging process. Most of them didn’t work. They were no better than snake oil.

There have been legitimate scientists investigating the effect of supplements, diets, and lifestyle on the aging process. Most of these studies have come up empty.

In this study (M Gagesch et al, Journal of Frailty And Aging, 12: 71-77, 2023) the authors hypothesized that a holistic approach might be better than individual interventions. They asked whether a combination of vitamin D3 supplementation, omega-3 supplementation, and exercise might be more effective at slowing the aging process than any one of them alone.

There was good reason for choosing each of these interventions:

  • Low 25-hydroxyvitamin D levels have been associated with frailty in several studies. But association studies do not prove cause and effect, and no randomized, placebo control studies have measured the effect of vitamin D supplementation on frailty.
  • Omega-3 fatty acids have been linked to skeletal muscle health, and some studies have suggested omega-3 supplementation may improve muscle function in older adults.
  • A recent study has reported that a supervised exercise program reduced frailty in older adults. The authors wanted to see if the same was true for unsupervised, at-home exercise program.

How Was This Study Done?

clinical studyThe data from this study were collected as part of the DO-HEALTH study, a 3-year, double-blind, randomized, placebo-controlled clinical trial designed to identify interventions that support healthy aging in European adults aged 70 and older.

Initially, 2,157 healthy, community-dwelling adults were enrolled from five countries (Switzerland, Germany, Austria, France, and Portugal). They were examined in clinical centers at the beginning of the study and years 1, 2, and 3, with phone follow-up at 3-month intervals.

Aging was measured by something called the frailty index. At each clinic visit the participants were evaluated in five areas:

  1. Weakness was measured as grip strength. Weakness was defined as being in the lowest quintile of grip strength for someone their age and gender.

2) Fatigue was defined as a positive answer to the question, “In the last month have you had too little energy to do the things you wanted to do?”

3) Involuntary weight loss was defined as >5% weight loss within a year.

4) Low gait speed was defined as <2 ft/sec walking speed.

5) Low activity level was defined as a response of, “Less than once a week” to the question, “How often do you engage in activities that require a low or moderate level of energy such as gardening, cleaning the car, or going on a walk?”

    • Participants with 0 positive items were classified as robust.
    • Those with 1 or 2 positive items were classified as pre-frail.
    • Those with 3 or more positive items were classified as frail.

Only those participants from the DO-HEALTH study classified as robust at the first clinical visit (1,137 participants) were included in this study. The study measured how many of them became pre-frail or frail during the average follow-up of 2.9 years.

The interventions were:

  • Capsules containing a total of 2,000 IU/day of vitamin D3 with sunflower oil capsules as a placebo.
  • Capsules containing a total of 1,000 mg of EPA and DHA in a 1:2 ratio with a sunflower oil capsule as a placebo.
  • Exercise consisting of an unsupervised strength-training routine for 30 minutes, 3 times per week.
  • In this case the control was an unsupervised joint-flexibility routine for 30 minutes, 3 times per week.

The interventions were done individually, two together (vitamin D + omega-3, vitamin D + exercise, omega-3 + exercise), and all three together (vitamin D + omega-3 + exercise).

The results were corrected for age, sex, and low-trauma falls in the preceding 12 months.

Finally, the study measured blood 25-hydroxyvitamin D levels and omega-3 levels at each office visit. They found:

  • 28% of the participants were deficient in vitamin D at the beginning of the study.
  • The interventions gave the expected increase in vitamin D and omega-3 status.

Can You Slow The Aging Process?

Older Couple Running Along BeachAt the end of 3 years:

  • 61.2% of the participants had declined from robust health to the pre-frail category.
  • 2.6% of the participants had declined from robust health to the frail category.

[Note: The terms “pre-frail” and “frail” are measures of aging which I have described above.]

The number of participants in the frail category were too small to obtain a statistically significant measure of the effects of vitamin D, omega-3s, and exercise on frailty, so I will only discuss the results measuring their effect on pre-frailty in this review. These results are:

  • None of these interventions had a statistically significant effect on aging by themselves, as measured by the transition from robust health to pre-frailty.
  • None of these interventions had a statistically significant effect on aging when combined in pairs, although the vitamin D3-omega-3 pair came close to significance (31% reduction in pre-frailty with a probability of 94% (probabilities of 95% and above are considered significant.))
  • However, the combination of vitamin D3, omega-3s, and exercise reduced the risk of aging by 39%, which was statistically significant (96% probability).

The authors concluded, “Robust, generally healthy and active older adults without major comorbidities [diseases], may benefit from a combination of high-dose, supplemental vitamin D3, marine omega-3s, and SHEP [unsupervised strength training] with regard to the risk of becoming pre-frail over 3 years.”

A Holistic Approach To Living Healthy Longer

holistic approachThis study was a double-blind, placebo-controlled study, which is the gold standard for clinical studies. It was also unusually large (1,137 participants) and long (3 years) for this kind of study.

It was also much better than most double-blind, placebo-controlled studies in that it included three interventions (vitamin D3 supplementation, omega-3 supplementation, and exercise) and looked at their effect on aging individually, in pairs, and all three together.

One take-home lesson from this study was that a holistic approach that included all 3 interventions was superior to any one of these interventions alone or in pairs.

But the most important take-home lesson is this:

If you asked your doctor what you should do to slow the aging process, he or she would probably tell you, “Exercise may help, but forget supplementing with extra vitamin D or omega-3s. They have no proven benefits.”

They would be correct based on studies of each of these interventions individually. And the studies they might quote would be double-blind, placebo-controlled studies, the gold standard of clinical studies.

But would that be the best advice. Clearly not. The best advice would be to follow a holistic approach and use all 3 interventions together.

Unfortunately, this is true for most studies of supplementation. Supplements are tested individually, as if they were “magic bullets”. And most of these studies come up short. They fail to find a significant benefit of supplementation.

Supplements are almost never tested holistically in combination with each other and other interventions, but that’s where the “magic” really happens.

If you are a regular reader of “Health Tips From The Professor”, this should come as no surprise to you. I have often shared the Venn diagram on the upper left and said that the sweet spot is when two or more of these interventions overlap.

Of course, this is the first study of its kind. More studies are needed. More importantly, we need studies to fill in the other parts of the Venn diagram. We need to ask about the effect of diet and obesity on aging. For example:

  • If we add a healthy diet to vitamin D, omega-3s, and exercise, can we reduce aging even more dramatically?
  • Is the effort it takes to lose excess weight worth it? Does adding it to diet, supplementation, and exercise reduce the aging process even more?

Of course, I think the answer to those questions is an unequivocal, “Yes”. Multiple studies have shown that both a healthy weight and a healthy diet help you live healthier longer.

But I am a scientist. Neither diet nor weight loss have been tested in combination with supplementation and exercise. I would like to see studies combining all these modalities in a single double-blind, placebo-controlled experiment.

So, what does this mean for you? If you want to slow the aging process, if you are in search of your personal “Fountain of Youth…

  • This study suggests that vitamin D3 supplementation (2,000 IU/day), omega-3 supplementation (1,000 mg of EPA + DHA), and an exercise program that emphasizes strength training can help you slow the aging process.

But that is only the beginning. I also recommend…

  • Including a healthy diet and a healthy weight in your anti-aging regimen.
  • Making sure your diet has enough protein and leucine, since older adults need more of both to maximize the benefits of strength training.
  • Including other supplements as evidence for their benefit in slowing the aging process becomes available.

The Bottom Line 

A recent double-blind, placebo-controlled study looked at the effect of vitamin D3 supplementation (2,000 IU/day), omega-3 supplementation (1,000 mg/day EPA + DHA in a 1:2 ratio), and an unsupervised strength training program on the aging process.

It differed from most other double-blind, placebo-controlled studies in that:

  • It was larger (1,137 participants) and longer (3 years) than most.
  • More importantly, each intervention was tested individually, in pairs, and all 3 together.

The study found that:

  • None of these interventions had a statistically significant effect on aging by themselves.
  • None of these interventions had a statistically significant effect on aging when combined in pairs, although the vitamin D3-omega-3 pair came close to significance.
  • However, the combination of vitamin D3, omega-3s, and exercise reduced the risk of aging by a statistically significant 39%.

One take-home lesson from this study was that a holistic approach that included all 3 interventions was superior to any one of these interventions alone or in pairs.

But the most important take-home lesson is this:

If you asked your doctor what you should do to slow the aging process, he or she would probably tell you, “Exercise may help, but forget supplementing with extra vitamin D or omega-3s. They have no proven benefits.”

They would be correct based on studies of each of these interventions individually. And the studies they might quote would be double-blind, placebo-controlled studies, the gold standard of clinical studies.

But would that be the best advice? Clearly not. The best advice would be to follow a holistic approach and use all 3 interventions together.

Unfortunately, this is true for most studies of supplementation. Supplements are tested individually, as if they were “magic bullets”. And most of these studies come up short. They fail to find a significant benefit of supplementation.

Supplements are almost never tested holistically in combination with each other and other interventions, but that’s where the “magic” really happens.

For more information on this study and my recommendations on how to slow the aging process read the article above.

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

 ___________________________________________________________________________

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

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

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

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

Health Tips From The Professor