Omega-3 Fish Oil Supplements Archives - Health Tips From The Professor

Are Omega-3 Supplements Safe?

July 9, 2024 by Dr. Steve Chaney

The Flaws And Blind Spots In This Study

Author: Dr. Stephen Chaney

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

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

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

“Fish Oil Supplements May Lead to Heart Problems”.

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

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

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

To answer these questions:

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

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

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

How Was The Study Done?

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

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

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

The participants were:

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

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

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

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

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

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

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

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

Are Omega-3 Supplements Safe?

Here is what the study found.

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

Increased the risk of atrial fibrillation by 13%.

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

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

- Decreased the risk of heart failure by 8%.

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

- Did not affect the risk of heart attack.

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

Decreased the risk of major cardiovascular events by 9%.

Decreased the risk of death by 8%.

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

Decreased the risk of heart attacks by 15%.

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

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

Decreased the risk of death by 8%.

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

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

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

I will discuss the significance of these observations below.

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

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

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

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

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

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

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

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

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

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

In response to the questions you are probably thinking:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This study is no different:

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

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

Once again, these data were completely ignored.

What Does This Study Mean For You?

This study made 3 major points:

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

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

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

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

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

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

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

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

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

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

No detectable increased risk of atrial fibrillation.

I recommend getting your Omega-3 Index determined, and if it is low, increasing your omega-3 intake to get it into the 8% range. Some people go from 4% to 8% more rapidly than others, so you may need to repeat the test several times to optimize your Omega-3 Index.

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

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

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

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

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

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

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

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

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

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

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

The Bottom Line

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

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

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

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

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

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

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

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

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

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

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

_______________________________________________________________________

About The Author

Dr. Chaney 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?

June 11, 2024 by Dr. Steve Chaney

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

Author: Dr. Stephen Chaney

Migraines 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

Our 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?

This 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?

As 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

The 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%.

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.

______________________________________________________________________________

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

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

____________________________________________________________________________

About The Author

Do Omega-3s Reduce Osteoarthritis Pain?

April 16, 2024 by Dr. Steve Chaney

How Do Rheumatoid And Osteoarthritis Differ?

Author: Dr. Stephen Chaney

This 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?

This 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?

When 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:

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?

This 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.

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.

_____________________________________________________________________________

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

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

_______________________________________________________________________

About The Author

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

March 26, 2024 by Dr. Steve Chaney

Where Do We Go From Here?

Author: Dr. Stephen Chaney

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

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

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

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

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

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

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

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

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

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

How Was The Study Done?

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

The patient demographics were:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This was perhaps the most significant finding from this study.

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

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

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

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

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

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

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

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

What Does This Study Mean For You?

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

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

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

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

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

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

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

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

Where Do We Go From Here?

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

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

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

Metabolic differences due to obesity and diseases like diabetes.

Gender, ethnicity, and age.

Design of the omega-3 supplement.

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

The Bottom Line

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

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

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

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

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

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

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

______________________________________________________________________________

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

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

_______________________________________________________________________

About The Author

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.

Do Omega-3s Reduce Cognitive Decline?

October 31, 2023 by Dr. Steve Chaney

Should You Supplement With Omega-3s?

Author: Dr. Stephen Chaney

Do 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?

Why 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?

This 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?

The 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?

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.

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.

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.

___________________________________________________________________________

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

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

Can Healthy Eating Help You Lose Weight?

September 27, 2022 by Dr. Steve Chaney

Who Benefits Most From A Healthy Diet?

Author: Dr. Stephen Chaney

Fad diets abound. High protein, low carb, low fat, vegan, keto, paleo – the list is endless. They all claim to be backed by scientific studies showing that you lose weight, lower your cholesterol and triglycerides, lower your blood pressure, and smooth out your blood sugar swings.

They all claim to be the best. But any reasonable person knows they can’t all be the best. Someone must be lying.

My take on this is that fad diet proponents are relying on “smoke and mirrors” to make their diet look like the best. I have written about this before, but here is a brief synopsis:

They compare their diet with the typical American diet.

- Anything looks good compared to the typical American diet.

- Instead, they should be comparing their diet with other weight loss diets. That is the only way we can learn which diet is best.

They are all restrictive diets.

- Any restrictive diet will cause you to eat fewer calories and to lose weight.

- As little as 5% weight loss results in lower cholesterol & triglycerides, lower blood pressure, and better control of blood sugar levels.

Simply put, any restrictive diet will give you short-term weight loss and improvement in blood parameters linked to heart disease, stroke, and diabetes. But are these diets healthy long term? For some of them, the answer is a clear no. Others are unlikely to be healthy but have not been studied long term. So, we don’t know whether they are healthy or not.

What if you started from the opposite perspective? Instead of asking, “Is a diet that helps you lose weight healthy long term?”, what if you asked, “Can healthy eating help you lose weight?” The study (S Schutte et al, American Journal of Clinical Nutrition, 115: 1-18, 2022) I will review this week asked that question.

More importantly, it was an excellent study. It compared a healthy diet to an unhealthy diet with exactly the same degree of caloric restriction. And it compared both diets to the habitual diet of people in that area. This study was performed in the Netherlands, so both weight loss diets were compared to the habitual Dutch diet.

How Was The Study Done?

This was a randomized controlled trial, the gold standard of clinical studies. The investigators recruited 100 healthy, abdominally obese men and women aged 40-70. At the time of entry into the study none of the participants:

Had diabetes.
Smoked
Had a diagnosed medical condition.
Were on a medication that interfered with blood sugar control.
Were on a vegetarian diet.

The participants were randomly assigned to:

A high-nutrient quality diet that restricted calories by 25%.
A low-nutrient-quality diet that restricted calories by 25%.
Continue with their habitual diet.

The study lasted 12 weeks. The participants met with a dietitian on a weekly basis. The dietitian gave them the foods for the next week and monitored their adherence to their assigned diet. They were advised not to change their exercise regimen during the study.

At the beginning and end of the study the participants were weighed, and cholesterol, triglycerides, and blood pressure were measured.

Can Healthy Eating Help You Lose Weight?

To put this study into context, these were not healthy and unhealthy diets in the traditional sense.

Both were whole food diets.
Both included fruits, vegetables, low-fat dairy, and lean meats.
Both restricted calories by 25%.

The diets were designed so that the “high-nutrient quality” diet had significantly more plant protein (in the form of soy protein), fiber, healthy fats (monounsaturated and omega-3 fats), and significantly less fructose and other simple sugars than the “low-nutrient-quality” diet.

At the end of 12 weeks:

Participants lost significant weight on both calorie-restricted diets compared to the group that continued to eat their habitual diet.

- That is not surprising. Any diet that successfully restricts calories will result in weight loss.

Participants on the high-nutrient quality diet lost 33% more weight than participants on the low-nutrient-quality diet (18.5 pounds compared to 13.9 pounds).

Participants on the high-nutrient quality diet lost 50% more inches in waist circumference than participants on the low-nutrient-quality diet (1.8 inches compared to 1.2 inches).

- This is a direct measure of abdominal obesity.

When the investigators measured blood pressure, fasting total cholesterol levels, and triglyceride levels:

These cardiovascular risk factors were significantly improved on both diets.

- Again, this would be expected. Any diet that causes weight loss results in an improvement in these parameters.

The reduction in total serum cholesterol was 2.5-fold greater and the reduction in triglycerides was 2-fold greater in the high-nutrient quality diet group than in the low-nutrient-quality diet group.

The reduction in systolic blood pressure was 2-fold greater and the reduction in diastolic blood pressure was 1.67-fold greater in the high-nutrient quality diet group than in the low-nutrient-quality diet group.

The authors concluded, “Our results demonstrate that the nutrient composition of an energy-restricted diet is of great importance for improvements of metabolic health in an overweight, middle-aged population. A high-nutrient quality energy-restricted diet enriched with soy protein, fiber, monounsaturated fats, omega-3 fats, and reduced in fructose provided additional health benefits over a low-nutrient quality energy-restricted diet, resulting in greater weight loss…and promoting an antiatherogenic blood lipid profile.”

In short, participants in this study lost more weight and had a better improvement in risk factors for heart disease on a high-nutrient-quality diet than on a low-nutrient-quality diet. Put another way, healthy eating helped them lose weight and improved their health.

Who Benefits Most From A Healthy Diet?

None of the participants in this study had been diagnosed with diabetes when the study began. However, all of them were middle-aged, overweight, and had abdominal obesity. That means many of them likely had some degree of insulin resistance.

Because of some complex metabolic studies that I did not describe, the investigators suspected that insulin resistance might influence the relative effectiveness of the two energy-restricted diets.

To test this hypothesis, they used an assay called HOMA-IR (homeostatic model assessment of insulin resistance). Simply put, this assay measures how much insulin is required to keep your blood sugar under control.

They used a HOMA-IR score of 2.5 to categorize insulin resistance among the participants.

Participants with a HOMA-IR score >2.5 were categorized as insulin-resistant. This was 55% of the participants.

Participants with a HOMA-IR score ≤2.5 were categorized as insulin-sensitive. This was 45% of the participants.

When they used this method to categorize participants they found:

Insulin-resistant individual lost about the same amount of weight on both diets.

Insulin-sensitive individuals lost 66% more weight on the high-nutrient-quality diet than the low-nutrient-quality diet (21.6 pounds compared to 13.0 pounds).

The investigators concluded, “Overweight, insulin-sensitive subjects may benefit more from a high- than a low-nutrient-quality energy-restricted diet with respect to weight loss…”

What Does This Study Mean For You?

Simply put this study confirms that:

Caloric restriction leads to weight loss, and…

Weight loss leads to improvement in cardiovascular risk factors like total cholesterol, triglycerides, and blood pressure.

- This is not new.

- This is true for any diet that results in caloric restriction.

This study breaks new ground in that a high-nutrient quality diet results in significantly better:

Weight loss and…

Reduction in cardiovascular risk factors…

…than a low-nutrient quality diet. As I said above, the distinction between a “high-nutrient-quality” diet and a “low-nutrient-quality” diet may not be what you might have expected.

Both diets were whole food diets. Neither diet allowed sodas, sweets, and highly processed foods.

Both included fruits, vegetables, grains, and lean meats.
Both reduced caloric intake by 25%.

- If you want to get the most out of your weight loss diet, this is a good place to start.

In this study the investigators designed their “high-nutrient-quality” diet so that it contained:

More plant protein in the form of soy protein.

- In this study they did not reduce the amount of animal protein in the “high-nutrient-quality” diet. They simply added soy protein foods to the diet. I would recommend substituting soy protein for some of the animal protein in the diet.

More fiber.

- The additional fiber came from substituting whole grain breads and brown rice for refined grain breads and white rice, adding soy protein foods, and adding an additional serving of fruit.

More healthy fats (monounsaturated and omega-3 fats).

- The additional omega-3s came from adding a fish oil capsule providing 700mg of EPA and DHA.

Less simple sugars. While this study focused on fructose, their high-nutrient-quality diet was lower in all simple sugars.

All these changes make great sense if you are trying to lose weight. I would distill them into these 7 recommendations.

Follow a whole food diet. Avoid sodas, sweets, and highly processed foods.

Include all 5 food groups in your weight loss diet. Fruits, vegetables, whole grains, dairy, and lean proteins all play an important role in your long-term health.

Eat a primarily plant-based diet. My recommendation is to substitute plant proteins for at least half of your high-fat animal proteins. And this study reminds us that soy protein foods are a convenient and effective way to achieve this goal.

Eat a diet high in natural fibers. Including fruits, vegetables, whole grains, beans, nuts, seeds, and soy foods in your diet is the best way to achieve this goal.

Substitute healthy fats (monounsaturated and omega-3 fats) for unhealthy fats (saturated and trans fats) in your diet. And this study reminds us that it is hard to get enough omega-3s in your diet without an omega-3 supplement.

Reduce the amount of added sugar, especially fructose, from your diet. That is best achieved by eliminating sodas, sweets, and highly processed foods from the diet. I should add that fructose in fruits and some healthy foods is not a problem. For more information on that topic, I refer you to a previous “Health Tips” article .

Finally, I would like to remind you of the obvious. No diet, no matter how healthy, will help you lose weight unless you cut back on calories. Fad diets achieve that by restricting the foods you can eat. In the case of a healthy diet, the best way to do it is to cut back on portion sizes and choose foods with low caloric density.

I should touch briefly on the third major conclusion of this study, namely that the “high-nutrient quality diet” was not more effective than the “low-nutrient-quality” diet for people who were insulin resistant. In one sense, this was not news. Previous studies have suggested that insulin-resistant individuals have more difficulty losing weight. That’s the bad news.

However, there was a silver lining to this finding as well:

Only around half of the overweight, abdominally obese adults in this study were highly insulin resistant.

- That means there is a ~50% chance that you will lose more weight on a healthy diet.

Because both diets restricted calories by 25%, insulin-resistant individuals lost weight on both diets.

- That means you can lose weight on any diet that successfully reduces your caloric intake. That’s the good news.

- However, my recommendation would still be to choose a high-nutrient quality diet that is designed to reduce caloric intake, because that diet is more likely to be healthy long term.

The Bottom Line

A recent study asked, “Can healthy eating help you lose weight?” This study was a randomized controlled study, the gold standard of clinical studies. The participants were randomly assigned to:

A high-nutrient quality diet that restricted calories by 25%.
A low-nutrient-quality diet that restricted calories by 25%.
Continue with their habitual diet.

These were not healthy and unhealthy diets in the traditional sense.

Both were whole food diets.
Both included fruits, vegetables, low-fat dairy, and lean meats.
Both restricted calories by 25%.

At the end of 12 weeks:

Participants on the high-nutrient quality diet lost 33% more weight than participants on the low-nutrient-quality diet (18.5 pounds compared to 13.9 pounds).

When the investigators measured cardiovascular risk factors at the end of 12 weeks:

The reduction in total serum cholesterol was 2.5-fold greater and the reduction in triglycerides was 2-fold greater in the high-nutrient quality diet group than in the low-nutrient-quality diet group.

The reduction in systolic blood pressure was 2-fold greater and the reduction in diastolic blood pressure was 1.67-fold greater in the high-nutrient quality diet group than in the low-nutrient-quality diet group.

For more details on this study, what this study means for you, and my 7 recommendations for a healthy weight loss diet, 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.

Can Diet Protect Your Mind?

September 13, 2022 by Dr. Steve Chaney

Which Diet Is Best?

Author: Dr. Stephen Chaney

Alzheimer’s is a scary disease. There is so much to look forward to in our golden years. We want to enjoy the fruits of our years of hard work. We want to enjoy our grandkids and perhaps even our great grandkids. More importantly, we want to be able to pass on our accumulated experiences and wisdom to future generations.

Alzheimer’s and other forms of dementia have the potential to rob us of everything that makes life worth living. What is the use of having a healthy body, family, and fortune if we can’t even recognize the people around us?

Alzheimer’s and other forms of dementia don’t happen overnight. The first symptoms of cognitive decline are things like forgetting names, where you left things, what you did last week. For most people it just keeps getting worse.

Can diet protect your mind? Recent studies have given us a ray of hope. For example, several meta-analyses have shown that adherence to the Mediterranean diet was associated with a 25-48% lower risk of cognitive decline and dementia.

However, there were several limitations to the studies included in these meta-analyses. For example:

For most of the studies the diet was assessed only at the beginning of the study. We have no idea whether the participants followed the same diet throughout the study. This means, we cannot answer questions like:

- What is the effect of long-term adherence to a healthy diet?

- Can you reduce your risk of cognitive decline if you switch from an unhealthy diet to a healthy diet?

These studies focused primarily on the Mediterranean diet. This leaves the question:

- What about other healthy diets? Is there something unique about the Mediterranean diet, or do other healthy diets also reduce the risk of cognitive decline?

This study (C Yuan et al, American Journal of Clinical Nutrition, 115: 232-243, 2022) was designed to answer those questions.

How Was The Study Done?

The investigators utilized data from The Nurse’s Health Study. They followed 49,493 female nurses for 30 years from 1984 to 2014. The average age of the nurses in 1984 was 48 years, and none of them had symptoms of cognitive decline at the beginning of the study.

The nurse’s diets were analyzed in 1984, 1986, and every 4 years afterwards until 2006. Diets were not analyzed during the last 8 years of the study to eliminate something called “reverse causation”. Simply put, the investigators were trying to eliminate the possibility that participants in the study might change their diet because they were starting to notice symptoms of cognitive decline.

The data from the dietary analyses were used to calculate adherence to 3 different healthy diets:

The Mediterranean diet.

The DASH diet. The DASH diet was designed to reduce the risk of high blood pressure. But you can think of it as an Americanized version of the Mediterranean diet.

The diet recommended by the USDA. Adherence to this diet is evaluated by something called the Alternative Healthy Eating Index or AHEI.

Adherence to each diet was calculated by giving a positive score to foods that were recommended for the diet and a negative score for foods that were not recommended for the diet. For more details, read the article.

In 2012 and 2014 the nurses were asked to fill out questionnaires self-assessing the early stages of cognitive decline. They were asked if they had more trouble than usual:

Remembering recent events or remembering a short list of items like a grocery list (measuring memory).

Understanding things, following spoken instructions, following a group conversation, or following a plot in a TV program (measuring executive function).

Remembering things from one second to the next (measuring attention).

Finding ways around familiar streets (measuring visuospatial skills).

The extent of cognitive decline was calculated based on the number of yes answers to these questions.

Can Diet Protect Your Mind?

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

At the beginning of the study in 1984 there were 49,493 female nurses with an average age of 48. None of them had symptoms of cognitive decline.

By 2012-2014 (average age = 76-78) 46.9% of them had cognitive decline and 12.3% of them had severe cognitive decline.

Using the data on dietary intake and the rating systems specific to each of the diets studied, the investigators divided the participants into thirds based on their adherence to each diet. The investigators then used these data to answer two important questions that no previous study had answered:

#1: What is the effect of long-term adherence to a healthy diet? To answer this question the investigators averaged the dietary data obtained every 4 years between 1984 and 2006 to obtain cumulative average scores for adherence to each diet. When the investigators compared participants with the highest adherence to various healthy diets for 30 years to participants with the lowest adherence to those diets, the risk of developing severe cognitive decline was decreased by:

40% for the Mediterranean diet.
32% for the DASH diet.
20% for the USDA-recommended healthy diet (as measured by the AHEI score).

#2: Can you reduce your risk of cognitive decline if you switch from an unhealthy diet to a healthy diet? To answer this question, the investigators looked at participants who started with the lowest adherence to each diet and improved to the highest adherence by the end of the study. This study showed that improving from an unhealthy diet to a healthy diet over 30 years decreased the risk of developing severe cognitive decline by:

20% for the Mediterranean diet.
25% for the DASH diet.

There were a few other significant observations from this study.

The inverse association between healthy diets and risk of cognitive decline was greater for nurses who had high blood pressure.

- This is an important finding because high blood pressure increases the risk of cognitive decline.

The inverse association between healthy diets and risk of cognitive decline was also greater for nurses who did not have the APOE-ɛ4 gene.

- This illustrates the interaction of diet and genetics. The APOE-ɛ4 gene increases the risk of cognitive decline. Healthy diets reduced the risk of cognitive decline in nurse with the APOE-ɛ4 gene but not to the same extent as for nurses without the gene.

This study did not investigate the mechanism by which healthy diets reduced the risk of cognitive decline, but the investigators speculated it might be because these diets:

Were anti-inflammatory.
Supported the growth of healthy gut bacteria.

The investigators concluded, “Our findings support the beneficial roles of long-term adherence to the [Mediterranean, DASH, and USDA] dietary patterns for maintaining cognition in women…Further, among those with initially relatively low-quality diets, improvement in diet quality was associated with a lower likelihood of developing severe cognitive decline. These findings indicate that improvements in diet quality in midlife and later may have a role in maintenance of cognitive function among women.”

Which Diet Is Best?

In a sense this is a trick question. That’s because this study did not put the participants on different diets. It simply analyzed the diets the women were eating in different ways. And while the algorithms they were using were diet-specific, there was tremendous overlap between them. For more specifics on the algorithms used to estimate adherence to each diet, read the article.

That is why the investigators concluded that all three diets they analyzed reduced the risk of cognitive decline rather than highlighting a specific diet. However, based on this and numerous previous studies the evidence is strongest for the Mediterranean and DASH diets.

And I would be remiss if I didn’t also mention the MIND diet. While it was not included in this study, the MIND diet:

Was specifically designed to reduce cognitive decline.

Can be thought of as a combination of the Mediterranean and DASH diets.

Includes data from studies on the mind-benefits of individual foods. For example, it recommends berries rather than all fruits.

The MIND diet has not been as extensively studied as the Mediterranean and DASH diets, but there is some evidence that it may be more effective at reducing cognitive decline than either the Mediterranean or DASH diets alone.

Which Foods Are Best?

The authors of this study felt it was more important to focus on foods rather than diets. This is a better approach because we eat foods rather than diets. With that in mind they analyzed their data to identify the foods that prevented cognitive decline and the foods increased cognitive decline. This is what they found:

Fruits, fruit juices, vegetables, fish, nuts, legumes, low-fat dairy, and omega-3 fatty acids (fish oil) reduced the risk of cognitive decline.

Red and processed meats, omega-6 fatty acids (most vegetable oils), and trans fats increased the risk of cognitive decline.

While this study did not specifically look at the effect of processed foods on cognitive decline, diets high in the mind-healthy foods listed above are generally low in sodas, sweets, and highly processed foods.

What Does This Study Mean For You?

The question, “Can diet protect your mind”, is not a new one. Several previous studies have suggested that healthy diets reduce the risk of cognitive decline, but this study breaks new ground. It shows for the first time that:

Long-term adherence to a healthy diet can reduce your risk of cognitive decline by up to 40%.

- This was a 30-year study, so we aren’t talking about “diet” in the traditional sense. We aren’t talking about short-term diets to drop a few pounds. We are talking about a life-long change in the foods we eat.

If you currently have a lousy diet, it’s not too late to change. You can reduce your risk of cognitive decline by switching to a healthier diet.

- This is perhaps the best news to come out of this study.

Based on current evidence, the best diets for protecting against cognitive decline appear to be the Mediterranean, DASH, and MIND diets.

And if you don’t like restrictive diets, my advice is to:

Eat more fruits, fruit juices, vegetables, fish, nuts, legumes, low-fat dairy, and omega-3 fatty acids (fish oil).

Eat less red and processed meats, omega-6 fatty acids (most vegetable oils), and trans fats.

Eat more plant foods and less animal foods.

Eat more whole foods and less sodas, sweets, and processed foods.

And, of course, a holistic approach is always best. Other lifestyle factors that help reduce your risk of cognitive decline include:

Regular exercise.
Weight control.
Socialization.
Memory training (mental exercises).

The Bottom Line

Alzheimer’s is a scary disease. What is the use of having a healthy body, family, and fortune if we can’t even recognize the people around us?

A recent study looked at the effect of diet on cognitive decline in women. The study started with middle-aged women (average age = 48) and followed them for 30 years. The investigators then used these data to answer two important questions that no previous study had answered:

#1: What is the effect of long-term adherence to a healthy diet? When the investigators compared participants with the highest adherence to various healthy diets for 30 years to participants with the lowest adherence to those diets, the risk of developing severe cognitive decline was decreased by:

40% for the Mediterranean diet.
32% for the DASH diet.
20% for the USDA recommendations for a healthy diet.

#2: Can you reduce your risk of cognitive decline if you switch from an unhealthy diet to a healthy diet? This study showed that improving from an unhealthy diet to a healthy diet over 30 years decreased the risk of developing severe cognitive decline by:

20% for the Mediterranean diet.
25% for the DASH diet.

For more details on the study, which diets, and which foods are best for protecting your mind, and what this study means for you, read the article above.

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

The Omega-3 Pendulum

April 12, 2022 by Dr. Steve Chaney

Who Benefits Most From Omega-3s?

Author: Dr. Stephen Chaney

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The Omega-3 Pendulum

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

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

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

The GISSI Study:

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

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

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

The ASCEND Study:

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

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

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

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

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

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

The VITAL Study:

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

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

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

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

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

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

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

- 26% in African Americans.

- 26% in patients with diabetes.

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

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

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

- 19% in patients with low fish intake.

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

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

- Deaths from heart attacks by 50%.

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

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

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

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

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

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

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

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

Who Benefits Most From Omega-3s?

The answers to this question are clear:

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

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

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

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

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

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

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

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

I feel the same way about omega-3s:

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

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

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

And omega-3s have other health benefits.

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

The Bottom Line

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

For the four questions you should ask when reviewing any omega-3 study and my recommendations for who benefits the most from omega-3 supplementation, read the article above.

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

Do Omega-3s Oil Your Joints?

March 30, 2021 by Dr. Steve Chaney

Fish Oil And Osteoarthritis

Author: Dr. Stephen Chaney

Osteoarthritis is not just painful. It is one of the leading causes of disability in this country. And because the joint pain associated with osteoarthritis limits activity levels, it is linked to:

Obesity

The diseases associated with obesity (diabetes and heart disease).

- Osteoarthritis increases the risk of heart disease by 50%.

Premature death associated with the increased prevalence of obesity, diabetes, and heart disease.

- Osteoarthritis increases the risk of all-cause mortality by 55%.

If osteoarthritis were rare, these statistics would just be an interesting side note. But osteoarthritis is the most common form of arthritis. It affects more than 32 million Americans. And it is costly. It costs the American economy:

$65 billion in health care costs.

$17 billion in lost wages.

$136 billion in total costs.

Conventional therapy for osteoarthritis is treatment with anti-inflammatory drugs, but they have side effects. They may even increase the risk of premature death in some individuals.

What about natural anti-inflammatory nutrients and phytonutrients? Two that have received a lot of press in recent years are omega-3s (fish oil) and curcumin.

A recent meta-analysis (NK Senftleber et al, Nutrients, 9: 42, 2017) of 42 clinical studies on the effects of omega-3s on various types of arthritis found that:

There is moderate quality evidence that omega-3s reduce the pain associated with rheumatoid arthritis. Basically, this means that there is strong, but not definitive, evidence that omega-3s reduce the pain of rheumatoid arthritis. Other general conclusions with respect to rheumatoid arthritis were:

- The best results were obtained from fish oil preparations with an EPA/DHA ratio of >1.5, suggesting that EPA is more beneficial than DHA.

- Early studies suggested that the optimal dose of omega-3s was ≥2.6 g/day for ≥12 weeks.

There was low quality evidence for an effect of omega-3s on osteoarthritis. Only 5 clinical trials have been published on the topic and the results of those studies are conflicting.

The data for an effect of curcumin on osteoarthritis pain are even more limited. There is some evidence it might be beneficial, but the studies are small and are conflicting.

In this week’s issue of “Health Tips From the Professor” I discuss an exploratory study (JC Kuszewski et al, Rheumatology Advances In Practice 4: 1-9, 2020) on the effect of omega-3s and curcumin on osteoarthritis pain.

How Was The Study Done?

You are probably wondering, “What is an “exploratory study?” Let me start by providing you with a little perspective from my years of heading a cancer research laboratory at the University of North Carolina:

Clinical studies are expensive. And if you are trying to study an approach that has not already proven to be successful, the money needed to fund the study can be hard to come by. It is a “Catch 22” situation. You need to conduct an “exploratory study” to show your project is likely to succeed before the funding agency will give you money to fund your project.

But where do you get the money to fund your exploratory project? One way that investigators overcome that barrier is to use data from a previous study that was originally designed for a different purpose. The study I will describe today is an example of that approach.

The study utilized data collected from a clinical trial designed to measure the effect of omega-3s and curcumin on brain function in older adults. The study recruited 152 older adults (average age = 65) who were overweight to obese (average BMI = 31) and sedentary (˂55 min/week of physical activity) from New South Wales, New Australia.

The participants were randomly divided into 4 groups:

Placebo group. [Note: The fish oil placebo contained 20 mg of fish oil so it would match the odor of the fish oil supplement, and the curcumin placebo contained yellow food dye so it would match the color of the curcumin supplement.]

Fish oil group (2,000 mg DHA & 400 mg EPA per day).

Curcumin group (160 mg/day curcumin).

Fish oil + curcumin group.

Participants were followed for 16 weeks. At the beginning and end of the study participants filled out questionnaires assessing (among other things):

The severity of their chronic osteoarthritis pain.

Disabilities caused by osteoarthritis in the participant’s daily life (physical distress, sleep disturbances, psychological distress, loss of productivity, physical limitations, physical deconditioning due to reduction in physical activity, and financial hardship).

Their physical and mental wellbeing during the past 4 weeks.

Their mood during the past 7 days.

Do Omega-3s Oil Your Joints?

The results were as follows:

Omega-3 supplementation reduced chronic osteoarthritis pain by 42%.

Omega-3 supplementation reduced disability associated with osteoarthritis by 40%.

- The reduction in pain and disability in participants supplemented with fish oil was greatest in those who reported the highest pain/disability at the beginning of the study.

- The reduction in pain was associated with an improved perception of physical and mental wellbeing.

- The reduction in pain was also associated with a decrease in depression and other mood disturbances.

Curcumin did not affect pain or osteoarthritis burden either alone or paired with omega-3s.

What Are The Pros And Cons Of This Study?

Pros:

The results for the effects of omega-3s on osteoarthritis were highly significant. In addition, the questionnaires used were well designed to capture the intensity and location of pain, mood, and feelings of wellbeing.

Cons:

This was an exploratory study using data collected from a study designed to measure the effect of omega-3s and curcumin on brain health in older adults. It was not ideally designed to measure the effect of omega-3s and curcumin on osteoarthritis.

If the original study had been intended for investigating the effect of these supplements on osteoarthritis, it would have been designed differently:

Participants would have been recruited into the study based on the presence and intensity of osteoarthritis pain.

The diagnosis of osteoarthritis would have been confirmed by X-rays.

Participants would have been admitted into the study only if they had moderate to severe osteoarthritis pain. Most of the participants in this study had only mild osteoarthritis pain. That may have limited the ability of this study to find an effect of curcumin on osteoarthritis pain.

The design of the omega-3 supplement would have been different.

- Because the original study was designed to determine the effect of omega-3s on brain health, the omega-3 supplement chosen had more DHA than EPA.

- Had the study been designed to determine the effect on omega-3s on an inflammatory disease like osteoarthritis, the omega-3 supplement would have had more EPA than DHA.

The curcumin supplement was also not ideally designed for this study. The curcumin supplement used in this study contained only 160 mg of curcumin and contained no other ingredients. Well-designed curcumin supplements usually contain around 500 mg curcumin standardized to 95% curcuminoids plus piperine to enhance the absorption of the curcumin.

In the words of the authors, “Further studies are warranted to evaluate the benefits of fish oil, alone or as an adjunct to pharmacotherapy, in patients diagnosed with osteoarthritis who suffer moderate-to-severe pain…” In other words, they now intend to use the data from this exploratory study to apply for funds to conduct a larger study specifically designed to measure the effects of omega-3s on osteoarthritis pain.

The study limitations described above, severely restricted the ability of the study to detect any beneficial effect of curcumin on osteoarthritis pain. The effect of curcumin on osteoarthritis pain is probably less than the effect of omega-3s, but it would be premature to conclude that it has no benefit. However, they obtained no data from their “exploratory study” to justify a follow-up study on the effect of curcumin on osteoarthritis pain.

Fish Oil And Osteoarthritis

This study suggests that 2.4 grams/day of omega-3s may be equally effective at reducing osteoarthritis pain and the effects that osteoarthritis pain has on both physical health and psychological health. However, because this study has several limitations, the evidence cannot be considered definite.

If you have either rheumatoid or osteoarthritis, I recommend trying omega-3 supplementation. Based on the studies described above, you might want to aim for 2-3 g/day of omega-3s with an EPA/DHA ration of 1.5 or greater.

As with any natural approach, this will work better for some people that for others. However, don’t forget that omega-3s are also important for heart health, healthy blood pressure, brain health, and a healthy pregnancy (https://www.chaneyhealth.com/healthtips/omega-3s-during-pregnancy-are-healthy/). If they also happen to reduce your arthritis pain, that is an extra benefit.

As usual, I recommend a holistic approach. You should also:

Follow an anti-inflammatory diet.

Keep active.

Aim for a healthy weight.

Add antioxidant and polyphenol supplements.

These lifestyle changes should allow you to reduce or eliminate any pain medication you may be taking.

Finally, if you are on blood thinners, consult with your physician before adding omega-3 supplements to your diet. My preference is to incorporate omega-3s and reduce other medications, but that is a discussion you need to have with your doctor.

The Bottom Line

A recent meta-analysis has concluded there is moderate quality evidence that omega-3s reduce the pain associated with rheumatoid arthritis. Basically, this means that there is strong, but not definitive, evidence that omega-3s reduce the pain of rheumatoid arthritis. Other general conclusions with respect to rheumatoid arthritis were:

The best results were obtained from fish oil preparations with an EPA/DHA ratio of >1.5, suggesting that EPA is more beneficial than DHA.

Earlier studies suggested that the optimal dose of omega-3s was ≥2.6 g/day for ≥12 weeks.

However, there have been few studies on the effect of omega-3s on osteoarthritis. A new exploratory study looked at the effect of 2.4 g/day of omega-3s for 16 weeks on the pain and disability associated with osteoarthritis. It found:

Omega-3 supplementation reduced chronic osteoarthritis pain by 42%.

Omega-3 supplementation reduced disability associated with osteoarthritis by 40%.

- The reduction in pain and disability in participants supplemented with fish oil was greatest in those who reported the highest pain/disability at the beginning of the study.

- The reduction in pain was associated with an improved perception of physical and mental wellbeing.

- The reduction in pain was also associated with a decrease in depression and other mood disturbances.

The authors concluded, “Our findings indicate potential for fish oil supplementation to reduce mild osteoarthritis pain and burden in sedentary overweight/obese older adults. Further studies are warranted to evaluate the benefits of fish oil, alone or as an adjunct to pharmacotherapy, in patients diagnosed with osteoarthritis who suffer moderate-to-severe pain…”

As with any natural approach, this will work better for some people that for others. However, don’t forget that omega-3s are also important for heart health, healthy blood pressure, brain health, and a healthy pregnancy. If they also happen to reduce your arthritis pain, that is an extra benefit.

As usual, I recommend a holistic approach. You should also:

Follow an anti-inflammatory diet.

Keep active.

Aim for a healthy weight.

Add antioxidant and polyphenol supplements.

These lifestyle changes should allow you to reduce or eliminate any pain medication you may be taking.

For more details read the article above.

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

How Much Omega-3s Do You Need?

March 5, 2019 by Dr. Steve Chaney

Can You Get The Omega-3s You Need From Diet Alone?

Author: Dr. Stephen Chaney

Two recent studies have provided strong evidence that omega-3s reduce the risk of heart attacks. However, both studies used high doses of omega-3s and did not do a dose-response analysis. That leaves you with several unanswered questions:

How much omega-3s do you need to significantly reduce your risk of heart attack?
Will that amount of omega-3s provide other health benefits?
Can you get that amount of omega-3s from diet alone?
Can you get that amount of omega-3s from supplementation alone?

Fortunately, a recent study (KH Jackson et al, Prostaglandins, Leukotrienes and Essential Amino Acids, 142: 4-10, 2019) has answered those questions. But, before we consider that article, we should look at a biomarker called “Omega-3 Index.”

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

The Omega-3 Index is a measure of the ratio between the heart-healthy omega-3 fats (EPA + DHA) and all the other fats in red blood cell membranes. It is considered an excellent measure of our omega-3 status.

Dr. William S Harris, one of the top experts in the omega-3 field, first proposed the Omega-3 Index as a biomarker for cardiac health back in 2007. Based on multiple clinical and population studies, he proposed that an Omega 3 Index of 4% was associated with high heart attack risk, and an Omega-3 Index of 8% was associated with low heart attack risk. This has been supported by a recent meta-analysis of 10 clinical studies showing that an Omega-3 Index of 8% was associated with a 35% reduction in cardiovascular death compared to an Omega-3 Index of 4%.

Other studies suggest that an Omega-3 Index of 8% is associated with:

A slower rate of telomere shortening.
A lower risk of death from any cause.
Reduction in symptoms of depression.
Improved recovery from a heart attack.
Reduction in arthritis symptoms.
Reduced age-related brain shrinkage in B-vitamin treated subjects. (I have written about the synergistic relationship between omega-3s and B vitamins with respect to brain health in a previous issue of “Health Tips From the Professor.”

(Note: You will find references to these studies in the paper I have cited.)

For reference, most Americans have an Omega-3 Index between 4 and 6%. In contrast, in Japan, where the incidence of heart disease is much lower, the Omega-3 Index ranges from 6.8% to 9%.

How Was The Study Designed?

The data for this study were derived from 3458 individuals who 1) sent in a dried blood spot to a commercial laboratory for determination of Omega-3 Index between March 30, 2017 and January 15, 2018, 2) filled out a short questionnaire about fish intake and omega-3 supplement use, and 3) were older than 18.

With respect to fish intake, the possible responses were “none per week,” “every other week,” “every week,” “2 times per week,” and “3 or more times per week.”

With respect to omega-3 supplement use, those who reported taking an omega-3 supplement were asked what kind of omega-3 supplement they were taking. Those who said they were taking a flaxseed oil supplement were excluded from the analysis because flaxseed oil contains no EPA or DHA.

The characteristics of the population studied were as follows:

84% came from the United States. The remaining 16% came from 27 other countries.
The average age was 51 years and 40% of the respondents were male.
62% ate little or no fish. The exact breakdown of fish consumption was:
- 5% ate no fish.
- 9% ate fish every other week.
- 6% ate fish weekly.
- 2% ate fish twice a week.
- 8% ate fish three or more times a week.

52% took omega-3 supplements. Of those taking omega-3 supplements, 84% were taking fish oil supplements.

How Much Omega-3s Do You Need?

The correlation between omega-3 intake and Omega-3 Index in these individuals was:

No fish = 4.5%.
- No fish + supplementation = 6.6%.

Bi-weekly = 4.8%
- Bi-weekly + supplementation = 6.9%

Weekly = 5.1%
- Weekly + supplementation = 7.3%

Twice weekly = 5.7%
- Twice weekly + supplementation = 7.8%

3+ times per week = 6.5%
- 3+ times per week + supplementation = 8.6%

The authors said: “We found that those with the best chance of achieving a desirable Omega-3 Index were reporting the consumption of at least 3 fish meals per week and were taking an EPA + DHA-containing omega-3 supplement.”

The authors further concluded that an EPA + DHA intake of around 835 mg per day or higher would be required to achieve an average Omega-3 Index of 8%. This was based on two assumptions:

A 4 once serving of oily fish provides around 1,200 mg of EPA + DHA.
The average omega-3 supplement provides around 300 mg of EPA + DHA.

What Are The Limitations Of The Study?

The two biggest limitations of the study are the assumptions that a serving of fish provides 1,200 mg of EPA + DHA and a fish oil supplement provides 300 mg of EPA + DHA.

Their dietary survey did not ask what kind of fish the respondents were consuming. Some fish provide much less than 1,200 mg of EPA + DHA per serving. This could have caused the authors to overestimate the contribution that fish intake made to the Omega-3 Index in their study.
Some omega-3 supplements provide more than 300 mg EPA + DHA, and some people take more than the recommended number of omega-3 capsules. This could have caused the authors to underestimate the contribution of omega-3 supplements to the Omega-3 Index in their study.

The major implication of these limitations comes when we look at the standard deviation of the correlations between omega-3 intake and Omega-3 Index.

Some people consuming 3 or more servings of fish per week had an Omega-3 Index of well above 8%. This suggests that diet alone can allow you to reach an optimal Omega-3 Index. This conclusion is also supported by dietary studies in Japan (see below).
Some people taking omega-3 supplements had an omega-3 index of above 8% even in the group consuming no fish. This suggests that supplementation alone can allow you to reach an optimal Omega-3 Index as long as your total EPA + DHA intake is 835 mg/day or greater.

These limitations may also affect the calculation of how much EPA + DHA we need to reach an optimal Omega-3 Index. For example, the most widely used omega-3 calculator estimates that you would need 950 mg of EPA + DHA to increase your Omega-3 Index from 4% to 8%.

What Does This Study Mean For You?

At the beginning of this article I said that this study answered 4 questions:

How much omega-3s do you need to significantly reduce your risk of heart attack?
- This study estimated that around 835 mg/day of EPA + DHA is needed to reach an Omega-3 Index of 8%, which previous studies have shown to be associated with low heart disease risk.
- This is similar to the 950 mg/day estimate from a widely used omega-3 calculator.
- There is considerable individual variability, but 835 – 950 mg/day is a good target for most people. If in doubt, I recommend that you get your Omega-3 Index tested.

Will that amount of omega-3s provide other health benefits?
- The evidence is strongest for heart health, but this paper lists other studies suggesting that a high Omega-3 Index is associated with reduced risk of depression, arthritis, age-related brain shrinkage & cognitive decline, and death from all causes.

Can you get that amount of omega-3s from diet alone?
- In this study an optimal Omega-3 Index was achieved only in the group that consumed 3 or more servings of fish per week and took an omega-3 supplement. However, not all those fish were rich in EPA + DHA.
- Previous studies have shown that Japanese who consume 3 or more servings per week of oily fish, rich in EPA + DHA, have an Omega-3 Index of 6.8% to 9%. This shows us it is possible to reach an optimal Omega-3 Index from diet alone.

Can you get that amount of omega-3s from supplementation alone?
- Here the answer is clearly yes. Based on this and other studies, it would require in the range of 835-950 mg/day from supplementation to reach an optimal Omega-3 Index for most people.

Here are some other conclusions from the authors of the study:

“The average Omega3 Index in Japan ranges from 6.8 to 9.0%…So, yes, an Omega-3 Index of >8% is achievable by diet alone. But Japan is fairly unique…The average Omega-3 Index for Americans ranges from 4 to 6%. So, short of adopting the Japanese diet for a lifetime, it appears that taking an EPA + DHA supplement could be an important strategy for achieving a cardioprotective Omega-3 Index.”
They consider current recommendations for omega-3 intake to be inadequate. Their recommended intake of 835 mg of EPA + DHA per day is:
- “>3 times the EPA + DHA recommended by the Dietary Guidelines for Americans (250 mg/day).”
- “1.7 times the amount recommended by the Academy of Nutrition and Dietetics (500 mg/day).”
- “8 times higher than the typical EPA + DHA intake in the US (~100 mg/day).”
The American Heart Association currently recommends the consumption of 1-2 seafood meals per week.
The authors commented: “We do recognize that public health recommendations must balance what is ideal vs. what is practical for the public and must also take into consideration…potentially hazardous components of fish (mercury, PCBs) and the sustainability of the world’s fish supply.”
However, they considered the recommendation of the American Heart Association to be woefully inadequate. Based on their data, they concluded: “To achieve an Omega-3 Index of >8%, either adding an EPA + DHA supplement or increasing to 4-5 servings of fish/week would be necessary.”

Because of the high level of contamination of the world’s fish supply, my personal preference would be to add a high purity omega-3 supplement to my diet rather than consuming fish multiple times a week. I love salmon, but I try to limit myself to a salmon dinner no more than once a month.

The Bottom Line

A recent study looked at how much EPA + DHA you would need to achieve an optimal omega-3 status. The investigators used a measurement called Omega-3 Index, which has been shown to be an excellent measurement of omega-3 status. They asked how much EPA + DHA from diet plus supplementation was required to achieve an Omega-3 Index of 8%, which is associated with a low risk for heart disease. The key findings from this study were:

Around 835 mg/day of EPA + DHA is needed to reach an Omega-3 Index of 8%.
This is similar to the 950 mg/day estimate from a widely used omega-3 calculator.
There is considerable individual variability, but 835 – 950 mg/day is a good target for most people. If in doubt, I recommend that you get your Omega-3 Index tested.
The Japanese eat EPA + DHA-rich fish 3 or more times per week and have an Omega-3 Index of 6.9 to 9.0%, so it is clearly possible to achieve an optimal Omega-3 Index from diet alone. However, the American diet is so different from the Japanese diet that the authors concluded: “Short of adopting the Japanese diet for a lifetime, it appears that taking an EPA + DHA supplement could be an important strategy for achieving a cardioprotective Omega-3 Index.”
The American Heart Association currently recommends the consumption of 1-2 seafood meals/week. The authors consider this recommendation to be woefully inadequate. They said: “To achieve an Omega-3 Index of >8%, either adding an EPA + DHA supplement or increasing to 4-5 servings of fish/week would be necessary.”

Because of the high level of contamination of the world’s fish supply, my personal preference is to add a high purity omega-3 supplement to my diet rather than consuming fish multiple times a week. I love salmon, but I try to limit myself to a salmon dinner no more than once a month.

For more details read the article above.

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