DHA

Omega-3 Supplements Are Safe

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Why Do Clinical Studies Disagree? 

Author: Dr. Stephen Chaney 

Pendulum
Pendulum

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

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

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

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

How Was This Study Done?

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

  • The studies were randomized trials that compared omega-3 supplements with placebo or standard treatment. Half the patients received the omega-3 supplement.
  • The patients were either previously diagnosed with heart disease or were at high risk of developing heart disease.
  • The studies reported the incidence of bleeding events.

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

Omega-3 Supplements Are Safe

Omega-3s And Heart DiseaseThe results were reassuring for omega-3 supplement users. When compared to a placebo or standard treatment, omega-3 supplements.

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

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

  • Increased the relative risk of bleeding by 50% compared to the control group.
    • While this sounds scary, the absolute risk of bleeding was only increased by 0.6% compared to the control group.
    • I will explain the difference between relative risk and absolute risk below. But for now, you can think of absolute risk as a much more accurate estimate of your actual risk.

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

  • High dose of EPA (4 gm/day) or…
  • Lack of DHA and other naturally occurring omega-3s in the formulation. The authors said:
    • The effect of DHA on the endothelial lining is weaker than that of EPA (EPA makes the endothelial lining “less sticky” which reduces its ability to trigger blood clot formation. This is one of the mechanisms by which EPA is thought to decrease blood clot formation.)
    • The ability of DHA to inhibit oxidation of Apo-B-containing particles was less sustained than that of EPA (Oxidized Apo-B-containing particles increase the risk of blood clot formation. Inhibition of that oxidation by EPA is another of the mechanisms by which EPA is thought to decrease blood clot formation.)

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

What Is The Difference Between Relative And Absolute Risk?

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

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

  • If the absolute risk of some event occurring in the general population was 40%, a 50% increase in relative risk would increase the absolute risk by 20% (40% X 0.5 = 20%) to give a total risk of 60% (40% + 20%). In this case, both the relative and absolute risk are significantly large numbers.
  • However, if the absolute risk in the general population was 1%, a 50% increase in relative risk would only increase the absolute risk to 1.5%, a 0.5% increase in absolute risk. In this case, the increase in relative risk appears significant, but it is misleading because the absolute increase in risk is a modest 0.5%.
  • The latter resembles the situation in this study when the authors compared bleeding events in patients receiving Vascepa to those receiving a placebo. The absolute risk of bleeding events in the control group was 1.2%. The risk of bleeding events in the Vascepa group was 1.8%. That is a 50% increase in relative risk but only a 0.6% increase in absolute risk.

Why Do Clinical Studies Disagree?

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

#1: What kind of study is it?

  • The previous study was an association study. It can only report on associations. It cannot determine cause and effect. Outcomes like atrial fibrillation and strokes could have been caused by unrelated variables in the population studied.
  • The current study was a meta-analysis of 11 randomized controlled clinical trials. Because the only difference between the two groups is that one received omega-3 supplements, it can determine cause and effect.

#2: How many people were in the study?

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

#3: How long was the study?

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

#4: How were participants selected?

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

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

Doctor With Patient#5: How was omega-3 intake monitored?

  • This was a significant flaw of the previous study. Use of omega-3 supplements was determined by a questionnaire administered when the subjects entered the study. No effort was made to determine whether the amount of omega-3s consumed remained constant during the 12-year study.
  • The clinical studies within the current meta-analysis were comparing intake of omega-3 supplements to placebo and monitored the use of the omega-3 supplements throughout the study.

#6: What is the dose-response?

  • This was another serious flaw of the previous study. There was no dose-response data.
  • The current study provided limited dose-response data. From the data they presented it appeared that the risk of bleeding events was only slightly dose-dependent except for the clinical study with the high dose (4 gm/day) EPA-only Vascepa drug. It was a clear outlier, which is why they analyzed the data from that study independently from the other studies.

#7: What outcomes were measured?

  • The only common outcome measured in the two studies was hemorrhagic stroke.
  • The previous study reported that omega-3 supplementation increased the risk of stroke by 5% in the general population. However:
    • That result just barely reached statistical significance.
    • It was a 5% increase in relative risk. The authors did not report absolute risk.
    • It was an association study, so it could not determine cause and effect.
  • The current study found omega-3 supplementation had no effect on the risk of stroke in a population that either had heart disease or were at high risk of heart disease.
    • The exception, of course, was the group taking the high dose Vascepa drug (see below).

Heart Disease Study#8: Was the risk clinically significant?

  • As I said above, the previous study only reported relative risk, which can be misleading. However, absolute risk can be calculated from their data. For example,
    • The risk of developing atrial fibrillation in the group taking omega-3 supplements was 4.4% (calculated from Table 2 of the manuscript). The authors said that represented a 13% increase in relative risk compared to the group not taking omega-3 supplements. This means the absolute (actual) increase in risk is about 0.6%.
    • The risk of stroke in the group taking omega-3 supplements was 1.5% (calculated from Table 2 of the manuscript). The authors said that represented a 5% increase in relative risk compared to the group not taking omega-3 supplements. This means the absolute (actual) increase in risk is about 0.08%.
  • In the current study the increased risk of stroke in the group taking the high-dose (4 gm/day) EPA-only Vascepa drug was 50% for relative risk, but only 0.6% for absolute risk.
    • The authors of the current study argued that, based on absolute risk, the risk of stroke for people taking Vascepa was “clinically insignificant”. I would argue the same is true for the results reported in the previous study and the headlines they generated.

#9: Who sponsored the study? 

  • The previous study was supported by the Bill and Melinda Gates Foundation, an organization that has no obvious interest in the outcome of the study.
  • The current study is sponsored by Amarin, the pharmaceutical company that manufactures and markets Vascepa.
    • However, to their credit, the authors made no effort to hide the negative data about Vascepa.
      • In fact, they highlighted the negative data, noted that the increased bleeding risk with Vascepa was different from the omega-3 supplements studied, and offered possible explanations for why a high potency, EPA-only supplement might increase the risk of bleeding more than a lower potency omega-3 supplement containing both EPA and DHA.
    • They did, however, choose to emphasize the 0.6% absolute increase in bleeding risk rather than the 50% relative increase in bleeding risk. However, as I noted above absolute risk is a more accurate way to report risk, especially when the risk in the control group is only 1.2%.

Perspective On This Comparison:

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

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

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

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

What Does This Study Mean For You?

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

  • The bleeding risk with Vascepa is not unique. There are some studies suggesting that high dose (3-4 gm/day) omega-3 supplements containing both EPA and DHA may increase bleeding risk, although probably not to the same extent as Vascepa.
  • An optimal Omega-3 Index of 8% is associated with a decreased risk of heart disease and does not appear to increase the risk of atrial fibrillation or bleeding events such as hemorrhagic stroke. And for most people, an 8% Omega-3 Index can be achieved with only 1-2 gm/day of omega-3s.

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

  • Be aware that high-dose (3-4 gm/day) of omega-3 supplements may cause an increased risk of atrial fibrillation and stroke, but the risk is extremely small.
  • Omega-3 supplementation in the 1-2 gm/day range appears to be both safe and effective.
  • I recommend getting your Omega-3 Index determined, and if it is low, increasing your omega-3 intake to get it into the 8% range.

The Bottom Line

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

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

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

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

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

_____________________________________________________________________________

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

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

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

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

_______________________________________________________________________

About The Author 

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

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

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

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

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

Does EPA Reduce Migraine Frequency?

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

Author: Dr. Stephen Chaney

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

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

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

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

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

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

Migraines can be triggered by:

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

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

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

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

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

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

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

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

How Was This Study Done?

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

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

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

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

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

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

Does EPA Reduce Migraine Frequency?

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

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

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

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

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

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

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

What This Study Means For Us And For You

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

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

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

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

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

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

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

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

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

The Bottom Line

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

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

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

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

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

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

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

 ______________________________________________________________________________

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

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

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

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

____________________________________________________________________________

About The Author 

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

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

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

Which Nutrients Prevent Prenatal Depression?

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What Does This Study Mean For You?

Author: Dr. Stephen Chaney 

Yes, you read the headline correctly. Everyone talks about postnatal depression. But prenatal depression is also a “thing”, especially during the third trimester.

  • Worldwide, 4-20% of women experience some degree of depression during the third trimester – with pregnant women in high-income countries at the lower end (4-10%) of depression risk.
  • In contrast, the incidence of postnatal depression is 10-15%.

It is probably no coincidence that the incidence of depression is greatest during the third trimester and during the postnatal period.

  • The third trimester is the most difficult part of pregnancy for many women.
  • When a woman brings her baby home from the hospital her orderly life becomes chaotic.

But what role does nutrition play?

  • While not definitive, many studies suggest that supplementation with B vitamins, especially folic acid, B6, and B12; omega-3 fatty acids; vitamin D; and iron reduce the risk of postnatal depression.
  • However, there is much less information on which nutrients reduce the risk of prenatal depression.

Based on studies suggesting both iron and vitamin D deficiencies may negatively impact mental health, the authors of this study (JL Evanchuk et al, The Journal Of Nutrition. 154, 174-184, 2024) set out to determine whether iron and/or vitamin D deficiencies increase the risk of prenatal depression during the first trimester.

How Was This Study Done?

Clinical StudyThe authors recruited 2189 newly pregnant mothers from Calgary and Edmonton in Ontario Canada between 2009 and 2012. Participants in the study visited clinics in the area upon entry into the study; midway through the first, second, and third trimesters; and at multiple timepoints up to 3 months during the postpartum period.

In addition to the usual pregnancy wellness tests, participants filled out a 24-hour dietary recall and a Supplemental Intake Questionnaire to determine intakes of iron and vitamin D.

Note: The participants were all advised to take some form of prenatal supplement during the study. That’s because prenatal supplements are considered “the standard of care” for pregnant woman, so it would be considered unethical not to include a prenatal supplement in this study.

At the mid-point of the second trimester blood samples were drawn and analyzed for biomarkers of iron and vitamin D insufficiency. For iron the biomarkers were serum ferritin, soluble transferrin receptor, and hepcidin. For vitamin D, the biomarkers were 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 3-epi-25-hydroxyvitamin D.

Iron deficiency was defined as serum ferritin levels <15 µg/L. Vitamin D insufficiency was defined as 25-hydroxyvitamin D levels < 75nmol/L. The other biomarkers were used to confirm these diagnoses.

Maternal depression was measured midway through the third trimester and ~3 months postpartum using 10-item questionnaire called the Edinburg Postnatal Depression Scale (EPDS). The EPDS ranks depression on a scale of 0 to 30, with a score of ≥13 considered an indication of likely depression.

The characteristics of the women enrolled in this study were:

  • Average age = 31.5
  • Average prepregnancy BMI = 23 (healthy weight).
  • Married or cohabitating with a partner = 97%.
  • Highly educated (college or postgraduate degree) = 68%.
  • Income above $70,000/year = 78%.
  • First child = 54%.
  • White = 80%.

Based on the Edinburg Depression Scale, probably depression for the 1822 women who completed the study was 5.6% during the third trimester and 4.4% 3 months postpartum.

Note: The low incidence of depression seen in this study was probably due to:

  • The women in this study were of high socioeconomic status and were receiving excellent healthcare.
  • The women in this study were taking prenatal supplements that provided both iron and vitamin D.

Which Nutrients Prevent Prenatal Depression? 

pregnant women taking vitaminsAs I mentioned when describing how the study was designed, all participants in this study were advised to take a prenatal supplement. Consequently:

  • 94% of the women in this study were taking a supplement containing iron with an average supplemental iron intake of 26 mg/day.
    • Note: The RDA for iron during pregnancy is 30 mg/day and most prenatal supplements provide 27 mg/day.
  • 68% of the women in this study were taking a supplement containing vitamin D, with an average supplemental vitamin D intake of 330 IU/day.
    • Note: The RDA for vitamin D during pregnancy is 600 IU/day, but most prenatal supplements provide far less than that.

When the investigators looked at iron and vitamin D status during the second trimester:

  • 63.3% of the women had adequate levels of both iron and vitamin D.
  • 14.8% of the women were low in vitamin D but had adequate iron levels.
  • 18.4% of the women were low in iron but had adequate levels of vitamin D.
  • 3.5% of the women were low in both iron and vitamin D.

RDAs are supposed to be enough to meet the nutrient requirements of 97-98% of healthy individuals, so it is perhaps surprising to see so many women with insufficient levels of iron (21.9%) and/or vitamin D (18.3%) in this study. This could be due to:

  • Insufficient intake.
    • This is a likely explanation for vitamin D because the supplements women were using in this study provided around half the recommended RDA for vitamin D and the women lived at a northern latitude where sun exposure makes a small contribution to vitamin D levels.
    • However, this is a less likely explanation for insufficient iron levels because the supplements provided 87% of the RDA for iron.
  • Inadequate RDAs. Studies like this one provide a rigorous test for the adequacy of existing RDAs. This study suggests the existing RDA for iron is adequate to meet the needs of ~80% of pregnant women, which is reassuring. However, it may need to be increased to reach the goal of meeting the iron requirements for 97-98% of pregnant women.

But the important question is whether the iron and vitamin D insufficiencies seen in this study mattered. The data suggested that they did.

  • For pregnant women with low iron, but adequate vitamin D levels in the second trimester, there was a small, but significant, increased risk of experiencing depression symptoms in the third trimester.
  • For pregnant women with low iron and vitamin D levels in the second trimester, the risk of experiencing depression symptoms in the third trimester increased by 2.2 points in the 30-point Edinburg Depression Scale.
    • This is equivalent to a 7.4% increased risk of depression from deficiencies of iron and vitamin D alone – and these are only 2 of at least 8 nutrients thought to be associated with maternal depression.

The authors concluded, “Maternal iron and vitamin D biomarkers, measured during midpregnancy, were independently associated with third trimester maternal depression symptoms…This investigation is one of the first to report on the combined adequacy of maternal iron and vitamin D status during pregnancy and its impact on maternal depression.

The novelty of this work reinforces the need to ask similar questions [with other nutrients and] in other pregnant populations. Future investigations should report on the status of multiple nutrients and explore their independent and combined impact on health outcomes of pregnant individuals and their children.”

What Does This Study Mean For You?

Questioning WomanDepression during pregnancy is bad for you. And because your fetus can sense your mood, it is bad for your baby. So, what should you do?

You can consult with your doctor about which antidepressants are safe to take during pregnancy. But the truth is there are no good choices. There are some antidepressants that are off limits. There are other antidepressants that appear to have little short-term risks, but we have no idea if there are long-term risks for your child.

So, what about natural approaches? Let’s start with nutrition.

The biggest takeaway from this study is that prenatal supplements may not be sufficient to prevent nutritional deficiencies that may cause prenatal depression for pregnant women.

  • This does not mean that every pregnant woman suffering prenatal depression should increase their iron and vitamin D levels.
  • However, if you are experiencing prenatal depression, you might want to ask your doctor about checking your iron and vitamin D status to determine if extra iron and/or vitamin D would be beneficial.

And to put this study into its proper perspective we need to remember that iron and vitamin D deficiencies are only two of many nutrients that may increase the risk of prenatal depression.

For example, in addition to iron and vitamin D, prenatal depression is associated with deficiencies of:

  • B vitamins, especially folate, B6 and B12. Most prenatal supplements provide the recommended RDA of folate for pregnant women, but not all contain RDA amounts of B6 and B12.
  • Calcium and magnesium. Very few prenatal supplements provide the recommended RDA for calcium and magnesium.
  • Omega-3s, especially DHA. Very few prenatal supplements provide DHA, and the few that do usually provide inadequate amounts of DHA.

So, when you are having your nutrition conversation with your doctor, you might not want to limit your conversation to iron and vitamin D.

Alternately, as I suggested last week’s issue of “Health Tips From the Professor”, you might wish to add a multivitamin supplement and an omega-3 supplement providing at least 300 mg of DHA plus EPA. This simple step would be sufficient to assure you have adequate levels of nutrients thought to be important for reducing the risk of prenatal depression.

And, of course, there are other lifestyle factors, as well. For example:

  • Diets high in highly processed foods are known to increase the risk of depression. And whole food, primarily plant-based diets decrease the risk of depression.
  • Overweight and obesity increase the risk of depression.
  • Regular exercise decreases the risk of depression.

The Bottom Line

A recent study looked at whether taking a prenatal supplement was sufficient to eliminate deficiencies of iron and vitamin D during pregnancy and whether deficiencies of these two nutrients during the second trimester of pregnancy increased the risk of depression during the third trimester.

When the investigators looked at iron and vitamin D status during the second trimester:

  • 14.8% of the women were low in vitamin D but had adequate iron levels.
  • 18.4% of the women were low in iron but had adequate levels of vitamin D.
  • 3.5% of the women were low in both iron and vitamin D.

But the important question is whether the iron and vitamin D insufficiencies seen in this study mattered. The data suggested that they did.

  • For pregnant women with low iron, but adequate vitamin D levels in the second trimester, there was a small, but significant, increased risk of experiencing depression symptoms in the third trimester.
  • For pregnant women with low iron and vitamin D levels in the second trimester, the risk of experiencing depression symptoms in the third trimester increased by 2.2 points in the 30-point Edinburg Depression Scale.
  • This is equivalent to a 7.4% increased risk of depression from deficiencies of iron and vitamin D alone.

When you consider that iron and vitamin D are just two of 8 or more nutrients thought to be important for preventing depression during pregnancy, the question becomes what you can do to decrease your risk of developing depression during pregnancy and after the birth of your child.

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

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

 ____________________________________________________________________________

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

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

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

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

___________________________________________________________________________

About The Author

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

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

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

What Nutrients Are Missing In Prenatal Supplements?

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Do These Deficiencies Matter?

Author: Dr. Stephen Chaney

healthy pregnancyIf you are a pregnant mom, nothing is more important than the health of your baby. And if you are pregnant or thinking of becoming pregnant, your doctor has probably recommended a prenatal supplement. But does the prenatal supplement he or she recommended provide you with all the nutrients you need?

In a previous issue of “Health Tips From the Professor” I shared two studies that suggested the answer is, “No”. Those studies concluded that most prenatal supplements had little or no vitamin K, choline, DHA, and iodine – all of which are essential for the health of your newborn baby. And while most prenatal supplements contained calcium, the amount they provided was far below recommended levels.

The authors of the first study also made the point that most women going on a prenatal supplement will probably discontinue taking their multivitamin supplement, so a good prenatal supplement should provide all the essential nutrients.

But they don’t. Folic acid, iron, calcium, and vitamin D have long been recognized as essential for a healthy pregnancy. So, virtually every prenatal supplement contained these four nutrients, although calcium is often present in suboptimal amounts. Beyond those four nutrients, the design of prenatal supplements is haphazard. Some contain vitamin K, choline, iodine, or DHA (often in suboptimal amounts). But almost none contain all four nutrients.

And when you consider the other essential nutrients you find in most multivitamins, prenatal supplements often come up empty. Is that a problem? That’s what this study (KM Godfrey et al, PLOS Medicine, 1-27, December 5, 2023) was designed to find out.

How Was This Study Done?

clinical studyThis was a double-blind, placebo-controlled clinical trial, the gold standard for clinical studies. The investigators recruited 1,729 women who were planning to get pregnant from England, Singapore, and New Zealand between 2015 and 2017.

The women were randomly split into two groups:

  • The control group received a supplement containing nutrients that were most frequently included in prenatal supplements in those countries (folic acid, iron, calcium, iodine, and beta-carotene).
  • The intervention group received a supplement containing those nutrients plus riboflavin, vitamin B6, vitamin B12, vitamin D, zinc, inositol, and probiotics).
  • Riboflavin, vitamin B6, vitamin B12, vitamin D, and zinc were included because they are included in most multivitamins but are often missing in prenatal supplements.
  • Inositol was included because some studies have suggested that inositol may reduce the risk of maternal hyperglycemia and gestational diabetes.

Blood samples to assess nutritional status were obtained from all women in the study before the trial started (baseline) and after 1 month of supplementation with either the control or intervention formulation.

Of the women entering the study, 512 went on to have a singleton (one child) pregnancy. For these women supplementation was continued until childbirth. Additional blood samples were obtained in early and late pregnancy and at 6 months postdelivery. [Note: no supplementation was provided to either group postdelivery. And this is also a period of time when most women would be breastfeeding.]

The blood samples were tested for:

  • Blood levels of folic acid, riboflavin, vitamin B6, vitamin B12, and vitamin D.
  • Functional biomarkers of deficiencies of each of these vitamins.

What Nutrients Are Missing In Prenatal Supplements?

Question MarkThere was no difference in maternal hyperglycemia or gestational diabetes between the control group and the intervention group supplemented with inositol, so I will focus on the other nutrients present in the intervention group.

At baseline when subjects were first entered into the study.

  • 29.2% of the subjects had low or marginal status for folic acid.
  • 82.0% of the subjects had low or marginal status for riboflavin.
  • 1.3% of the subjects had low or marginal status for vitamin B6.
  • 9.1% of the subjects had low or marginal status for vitamin B12.
  • 48.7% of the subjects had low or marginal status for vitamin D.
  • 91.0% of the subjects had low or marginal status for one or more of these vitamins.

In the control group receiving folic acid but no riboflavin, vitaminB6, vitamin B12, and vitamin D:

  • Folic acid deficiency fell to 4.1% after 1 month of supplementation (the supplement used by the control group contained folic acid), 1% in early pregnancy, 6.1% in late pregnancy, and rose to 31.8% 6 months after supplementation was discontinued. The intervention group got the same amount of folic acid, and their results were similar.
  • Riboflavin deficiency ranged from 82-92% during pregnancy and returned to 82% 6 months postdelivery.
  • Vitamin B6 deficiency increased to 54% in late pregnancy and returned to 1.2% 6 months postdelivery.
  • Vitamin B12 deficiency increased to 55% in late pregnancy and returned to 12.4% 6 months postdelivery.
  • Vitamin D deficiency ranged from 35-43% during pregnancy and returned to 31% 6 months postdelivery.
  • Functional markers of vitamin B6 deficiency were evident by late pregnancy.

In short, data from the control group fell into 3 categories:

  • The data with folic acid confirm previous studies showing that folic acid in the amount present in most prenatal supplements is effective at preventing folic acid deficiency before and during pregnancy. It also strengthens the argument for continuing folic acid supplementation during breastfeeding.
  • Deficiencies of riboflavin and vitamin D are prevalent in women of childbearing age, but pregnancy does not appear to significantly impact the percentage of women who are deficient in these nutrients.
  • Deficiencies of vitamins B6 and B12 are rare in women of childbearing age, but pregnancy significantly depletes both nutrients.
    • This was particularly evident for vitamin B6. Blood levels of vitamin B6 markers decreased to a level that could impact the functioning of vitamin B6-depended metabolic pathways.

pregnant women taking vitaminsFor the intervention group receiving additional riboflavin, vitamin B6, vitamin B12, and vitamin D:

  • Deficiencies of these vitamins were eliminated by one month of supplementation.
  • Vitamin levels remained adequate during pregnancy.
  • Except for vitamin B12, deficiencies of these vitamins reappeared when supplementation was discontinued for 6 months. The maintenance of adequate B12 levels 6 months after supplementation stopped was expected because the body holds on to its B12 stores very tightly.

In short deficiencies of these nutrients before and during pregnancy could be eliminated by supplementation with levels of these nutrients found in many multivitamins.

The authors concluded, “Over 90% of the trial participants had low concentrations of one or more of folate, riboflavin, vitamin B12, or vitamin D during preconception, and many developed markers of vitamin B6 deficiency in late pregnancy. Preconception/pregnancy supplementation in amounts available in over-the-counter supplements substantially reduces the prevalence of vitamin deficiency and depletion markers before and during pregnancy, with higher maternal plasma vitamin B12 maintained during the recommended lactation period.”

Do These Deficiencies Matter?

New ParentsIt is well established that deficiencies of folic acid and vitamin D cause health risks for the mother and developmental risks for the fetus, so I won’t discuss these nutrients here.

However, the effect of riboflavin, vitamin B6, and vitamin B12 deficiencies on pregnancy is less well known, which is probably why these nutrients are often not added to prenatal supplements.

The authors of the study said small studies have suggested that:

  • Low or deficient riboflavin status may be associated with a higher risk of anemia during pregnancy.
  • Low vitamin B6 status may be associated with an increased risk of preterm birth and development of metabolic health risks in the child.
  • Low vitamin B12 status may be associated with increased risk of gestational diabetes and pre-eclampsia in the mother, and increased risk of neural tube defects, preterm birth, low birth weight, and neurocognitive delays in the baby – with the strongest evidence being an effect on neurocognitive development.

While none of these risks have been definitively proven, the authors point out that deficiencies of these nutrients can easily be eliminated with inexpensive, over-the-counter multivitamin supplements.

What Does This Study Mean For You?

Questioning WomanPerhaps I should start this section by asking why these deficiencies are so common in women of child-bearing age.

The authors speculate that part of the reason is that many women are giving up meat (B12 and iron) and dairy (calcium and riboflavin) for health or environmental reasons.

However, they also point out that a more likely cause is that more than 60% of calories consumed in countries like England, New Zealand, and the United States comes from ultra-processed foods – otherwise known as “empty calories”.

Whatever the cause, the authors conclude, “…the findings suggest a need to reappraise dietary recommendations for preconception and pregnancy to consider further the role of multiple micronutrient supplements for women living in higher-income countries.” I agree.

In a previous “Health Tips From the Professor” article, I reported a recent study showing that most prenatal supplements have either no or inadequate amounts of vitamin K, choline, DHA, iodine, and calcium, nutrients that are absolutely essential for a healthy pregnancy. And I gave recommendations for choosing the best prenatal supplement for you and your child.

That study also noted that many women discontinue their multivitamin supplement when they start taking a prenatal supplement. The current study indicates that practice may be unwise. It shows that:

  • Many women of childbearing age are deficient in one or more of these essential nutrients, and…
  • Essential nutrients not found in most prenatal supplements may also be important for a healthy pregnancy.

So, if you are pregnant or thinking of becoming pregnant, follow this article’s recommendation to start with a well-designed prenatal supplement that provides adequate amounts of folate, iron, calcium, vitamin D, vitamin K, choline, DHA, and iodine and add a multivitamin supplement that provides the other essential nutrients. Alternatively, a simpler approach would be to choose a well-designed prenatal supplement that includes all the essential nutrients. That would be my recommendation.

I would also note this study showed that deficiencies of most of these nutrients reappeared as soon as supplementation was discontinued. Although the authors of this study did not mention it, this reinforces the importance of continuing supplementation during breastfeeding.

The Bottom Line

I have previously reported on a study that concluded many prenatal supplements lack one or more nutrients shown to be important for a healthy pregnancy. But let’s say you have found a prenatal supplement that provides all those nutrients. Is that enough?

Studies show that most women stop taking their multivitamin supplement when they start on a prenatal supplement. But is that a good idea? Are there essential nutrients found in multivitamins, but not in many prenatal supplements that are also important for a healthy pregnancy?

A recent study asked that question in women who were trying to become pregnant. The study found that:

  • Many women of childbearing age are deficient in one or more essential nutrients found in multivitamin supplements but often missing in prenatal supplements, and…
  • Essential nutrients not found in most prenatal supplements may also be important for a healthy pregnancy.

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

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

 ______________________________________________________________________________

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

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

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

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

 ______________________________________________________________________

About The Author 

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

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

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

Do Omega-3s Reduce Osteoarthritis Pain?

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How Do Rheumatoid And Osteoarthritis Differ?

Author: Dr. Stephen Chaney 

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

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

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

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

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

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

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

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

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

How Do Rheumatoid And Osteoarthritis Differ?

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

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

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

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

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

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

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

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

How Was This Study Done?

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

The criteria for inclusion in the meta-analysis were:

1) The articles were written in English.

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

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

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

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

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

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

Do Omega-3s Reduce Osteoarthritis Pain?

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

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

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

What Are The Strengths and Limitations Of This Study?

strengths and weaknessesStrengths:

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

Limitations:

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

What Does This Study Mean For You?

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

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

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

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

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

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

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

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

The Bottom Line

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

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

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

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

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

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

_____________________________________________________________________________

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

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

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

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

_______________________________________________________________________

About The Author 

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

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

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

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

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What Does This Study Mean For You?

Author: Dr. Stephen Chaney

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

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

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

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

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

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

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

How Was This Study Done?

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

The studies included in this meta-analysis:

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

The meta-analysis excluded studies that:

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

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

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

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

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

When the investigators looked at subgroups within the studies:

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

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

I should probably explain the reasoning behind this conclusion.

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

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

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

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

What Does This Study Mean For You?

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

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

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

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

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

The Rest Of The Story

ProfessorThere are four additional points I would like to make:

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

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

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

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

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

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

The Bottom Line 

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

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

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

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

 ______________________________________________________________________________

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

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

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

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

About The Author 

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

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

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

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

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Where Do We Go From Here? 

Author: Dr. Stephen Chaney 

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

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

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

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

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

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

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

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

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

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

How Was The Study Done?

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

The patient demographics were:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This was perhaps the most significant finding from this study.  

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

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

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

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

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

  • Those with an increase in omega-3 index of ≥ 5% had a 2.9% annual risk of suffering major adverse cardiac events compared to a 7.1% annual risk for those with an increase of <5%.
  • That’s a risk reduction of almost 60%, and it was highly significant.

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

What Does This Study Mean For You? 

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

  • If you are on a blood thinning medication, the dose of either the medication or the omega-3 supplement may need to be reduced to prevent complications due to excess bleeding.
  • In addition, the investigators excluded patients from this study who might suffer adverse effects from omega-3 supplementation. This is a judgement only your doctor can make.

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

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

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

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

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

Where Do We Go From Here?

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

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

  • Diet, especially the presence of other fats in the diet.
  • Metabolic differences due to obesity and diseases like diabetes.
  • Gender, ethnicity, and age.
  • Design of the omega-3 supplement.

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

The Bottom Line 

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

  • When they simply compared omega-3 supplementation with the placebo there was no effect of omega-3 supplementation on cardiac outcomes.
  • However, when they based their comparison on the omega-3 index (a measure of how efficiently the omega-3s were absorbed and incorporated into cell membranes), the group with the highest omega-3 index experienced a 60% reduction in adverse cardiac events over the next 6.6 years.

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

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

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

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

 ______________________________________________________________________________

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

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

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

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

_______________________________________________________________________

About The Author 

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

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

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

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

Do Omega-3s Reduce Cognitive Decline?

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Should You Supplement With Omega-3s?

Author: Dr. Stephen Chaney 

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

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

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

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

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

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

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

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

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

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

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

How Was This Study Done?

clinical studyThis study consisted of two parts:

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

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

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

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

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

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

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

Do Omega-3s Reduce Cognitive Decline?

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

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

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

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

The authors concluded that,

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

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

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

Should You Supplement With Omega-3s?

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

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

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

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

The Bottom Line 

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

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

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

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

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

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

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

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

For more information on this study read the article above.

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

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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

 

 

Health Tips From The Professor