EPA Archives - Health Tips From The Professor

Do Omega-3s Reduce Osteoarthritis Pain?

April 16, 2024 by Dr. Steve Chaney

How Do Rheumatoid And Osteoarthritis Differ?

Author: Dr. Stephen Chaney

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

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

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

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

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

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

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

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

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

How Do Rheumatoid And Osteoarthritis Differ?

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

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

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

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

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

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

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

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

How Was This Study Done?

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

The criteria for inclusion in the meta-analysis were:

1) The articles were written in English.

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

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

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

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

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

Sample size (47-1221), Average = 230.

Mean age (55.9-68), Average = 63.

% men (13.8-45.1%), Average = 31%.

Omega-3 (EPA + DHA) dose (350 mg/day – 2,400 mg/day), Average = 1,085 mg/day.

Do Omega-3s Reduce Osteoarthritis Pain?

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

Reduced joint pain by 29% compared to the placebo.

Increased joint mobility by 21% compared to the placebo.

Was not associated with any adverse effects.

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

What Are The Strengths and Limitations Of This Study?

Strengths:

All the studies included in this meta-analysis were randomized, double-blind, placebo-controlled studies (the gold standard for clinical trials).

All the individual studies that qualified for this meta-analysis found that omega-3 supplementation reduced joint pain and improved joint mobility. This improves confidence that the conclusions of the meta-analysis are correct. The meta-analysis simply improved the statistical significance of this conclusion by combining the data from the individual studies.

Limitations:

The biggest limitation was that the individual studies included in this meta-analysis were not performed under the guidelines of the “Fatty Acids and Outcomes Research Consortium” that I discussed in last week’s issue of “Health Tips From the Professor”.

- The “Fatty Acids and Outcomes Research Consortium” guidelines harmonize the designs of individual studies, which strengthens the meta-analysis.

- - In contrast, the design of the individual studies within this meta-analysis was very different, which prevented the meta-analysis from being able to determine the optimal dose of omega-3 supplements and the minimum time required for omega-3 supplementation to significantly reduce the symptoms of osteoarthritis.

- The “Fatty Acids and Outcomes Research Consortium” guidelines would have also required these studies to measure tissue levels of omega-3s (something called Omega-3 Index) at the beginning and end of each study. This was not done in any of these studies.

- - This is important because if a patient’s tissue levels of omega-3s at the beginning of the study were already in the optimal range, you would expect little additional benefit from supplementation for that patient.

All the individual studies were very small. This limits the ability of these studies to provide definitive conclusions. Unfortunately, this is probably unavoidable.

- Double blind, placebo-controlled clinical studies are expensive. Only major pharmaceutical companies have the multi-million-dollar budgets required to conduct large double blind, placebo-controlled clinical studies that would provide more definitive evidence that omega-3 supplementation reduces the symptoms of osteoarthritis – and the follow-up studies that would determine the optimal dose of omega-3 supplements and the minimum time required to show an effect of omega-3 supplementation.

The patients in these studies were already taking medications to reduce their osteoarthritis symptoms prior to entering the study and were instructed to continue taking those medications during the study. This means that the studies were not asking whether omega-3s alone were effective at reducing osteoarthritis symptoms. They were asking whether omega-3 supplementation provided any additional benefits for people who were already taking medications to reduce symptoms.

- Unfortunately, this is also probably unavoidable. Current guidelines consider it unethical to withhold the medical “standard of care” from any patient in a clinical trial.

What Does This Study Mean For You?

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

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

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

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

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

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

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

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

The Bottom Line

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

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

Reduced joint pain by 29% compared to the placebo.

Increased joint mobility by 21% compared to the placebo.

Was not associated with any adverse effects.

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

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

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

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

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

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

_______________________________________________________________________

About The Author

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

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

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

The Good News About Omega-3s And Stroke

April 9, 2024 by Dr. Steve Chaney

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

Author: Dr. Stephen Chaney

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

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

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

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

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

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

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

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

EPA and DHA have been shown to:

Reduce inflammation, which is associated with increased risk of heart disease and stroke.

Reduce blood pressure. High blood pressure damages the endothelial lining of blood vessels, which can lead to either build up of atherosclerotic plaque or rupturing of the blood vessels.

Reduce platelet aggregation and blood viscosity, which reduces the potential for inappropriate blood clots forming in the carotid arteries.

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

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

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

In a previous clinical study 4 gm/day of purified EPA without DHA was associated with a slightly increased risk of bleeding events but did not increase the risk of hemorrhagic stroke.

High doses of pharmaceutical grade EPA have also been associated with a slightly increased risk of atrial fibrillation (Afib). In contrast, previous studies have shown that higher dietary intake of EPA + DHA are associated with a lower risk of Afib.

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

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

How Was This Study Done?

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

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

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

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

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

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

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

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

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

The Good News About Omega-3s and Stroke

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

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

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

For EPA + DHA risk was reduced by 17% for total stroke and 18% for ischemic stroke. There was no effect on hemorrhagic stroke.

For EPA risk was reduced by 17% for total stroke and 18% for ischemic stroke. There was no effect on hemorrhagic stroke. (You are probably starting to detect a pattern).

For DHA the results were only slightly different. Risk reduction was 12% for total stroke and 16% for ischemic stroke. There was no effect on hemorrhagic stroke.

For DPA, a minor component of the Omega-3 Index, there was no significant effect on total, ischemic, or hemorrhagic stroke.

There was a linear dose-response for the effect of EPA, DHA, and the two combined on the reduction in risk for both total and ischemic stroke.

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

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

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

What Does This Study Mean For You?

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

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

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

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

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

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

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

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

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

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

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

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

As I mentioned above, a previous clinical trial showed an increased risk of bleeding events and Afib at a dosage of 4 gm/day of pure EPA. We don’t know whether that was because of the dose or the use of a formulation that contained only EPA without DHA and other naturally occurring long-chain omega-3s.

In that study the increase in bleeding events and Afib was observed in <5% of participants, which suggests that those side effects may be limited to certain high-risk individuals.

- In this context, high risk might include individuals with preexisting Afib, individuals with a tendency towards excess bleeding, and patients on blood thinning medications.

- However, only your physician knows all your risk factors. If you have health issues or are on medications, it is always a good idea to check with your physician before changing your omega-3 intake. And if you are considering high-dose omega-3 supplementation or exceeding an 8% Omega-3 Index, I strongly recommend that you consult with your physician first.

The Bottom Line

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

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

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

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

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

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

_______________________________________________________________________________

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

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

April 2, 2024 by Dr. Steve Chaney

What Does This Study Mean For You?

Author: Dr. Stephen Chaney

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

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

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

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

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

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

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

How Was This Study Done?

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

The studies included in this meta-analysis:

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

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

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

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

Included approximately equal numbers of men and women.

The meta-analysis excluded studies that:

Lacked a placebo.

Lasted less than 4 weeks.

Included blood pressure medications.

Included individuals with preexisting cardiovascular events.

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

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

When the investigators combined the data from all 71 studies:

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

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

When the investigators looked at subgroups within the studies:

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

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

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

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

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

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

There were no significant differences between:

- Diet versus supplementation.

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

- Sex.

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

I should probably explain the reasoning behind this conclusion.

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

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

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

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

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

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

What Does This Study Mean For You?

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

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

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

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

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

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

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

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

The Rest Of The Story

There are four additional points I would like to make:

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

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

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

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

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

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

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

The Bottom Line

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

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

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

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

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

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

______________________________________________________________________________

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

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

About The Author

Can Healthy Eating Help You Lose Weight?

September 27, 2022 by Dr. Steve Chaney

Who Benefits Most From A Healthy Diet?

Author: Dr. Stephen Chaney

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

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

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

They compare their diet with the typical American diet.

- Anything looks good compared to the typical American diet.

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

They are all restrictive diets.

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

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

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

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

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

How Was The Study Done?

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

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

The participants were randomly assigned to:

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

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

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

Can Healthy Eating Help You Lose Weight?

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

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

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

At the end of 12 weeks:

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

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

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

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

- This is a direct measure of abdominal obesity.

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

These cardiovascular risk factors were significantly improved on both diets.

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

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

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

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

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

Who Benefits Most From A Healthy Diet?

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

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

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

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

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

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

When they used this method to categorize participants they found:

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

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

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

What Does This Study Mean For You?

Simply put this study confirms that:

Caloric restriction leads to weight loss, and…

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

- This is not new.

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

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

Weight loss and…

Reduction in cardiovascular risk factors…

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

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

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

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

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

More plant protein in the form of soy protein.

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

More fiber.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The Bottom Line

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

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

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

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

At the end of 12 weeks:

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

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

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

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

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

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

How Much Omega-3s Do Children Need?

September 6, 2022 by Dr. Steve Chaney

What Does This Study Mean For Your Children?

Author: Dr. Stephen Chaney

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

How Was The Study Done?

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

All studies were placebo controlled randomized clinical trials.

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

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

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

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

The dose of omega-3s.

- The relative amount of DHA and EPA.

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

How cognition (ability to learn) was measured.

The age of the children.

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

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

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

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

How Much Omega-3s Do Children Need?

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

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

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

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

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

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

What Does This Study Tell Us?

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

This study does not:

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

Define optimal levels of DHA + EPA.

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

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

This study does:

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

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

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

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

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

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

What Does This Study Mean For Your Children?

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

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

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

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

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

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

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

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

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

The Bottom Line

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

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

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

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

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

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

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

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

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

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

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

Omega-3s Reduce Preterm Births

August 9, 2022 by Dr. Steve Chaney

Do Omega-3s Make For A Healthy Pregnancy?

Author: Dr. Stephen Chaney

The role of omega-3s on a healthy pregnancy has been in the news for some time. Claims have been made that omega-3s reduce preterm births, postnatal depression, and improve cognition, IQ, vision, mental focus, language, and behavior in the newborn as they grow.

The problem is that almost all these claims have been called into question by other studies. If you are pregnant or thinking of becoming pregnant, you don’t know what to believe.

Should you eat more fish?
Should you take omega-3 supplements?
Or should you just ignore the claims about omega-3s and a healthy pregnancy?

These are not trivial questions. Let’s consider preterm births as an example. The medical profession has made enormous advances in keeping premature babies alive. However, premature babies are still at higher risk of several health conditions including:

Visual impairment.
Developmental Delay.
Learning difficulties.

Plus, it is expensive to keep premature babies alive. One recent study estimated that increasing omega-3 intake during pregnancy could reduce health care costs by around $6 billion in the United Stated alone.

Unfortunately, it’s not just omega-3s and pregnancy. The same is true for almost all nutritional health claims. One day a study comes out claiming that nutrient “X” cures some disease or has some miraculous benefit. The bloggers and news media hype that study. Suddenly you see that health claim everywhere. It becomes so omnipresent that you are tempted to believe it must be true.

But wait. A few months later another study comes to opposite conclusion. Now the media is telling you that health claim is false. The months come and go, and new studies keep coming out. Some support the health claim. Others refute it.

Pretty soon the nutrition headlines just become “noise”. You don’t know what to believe. If you want the truth, “Who ya gonna call?”

Who Ya Gonna Call?

It’s not Ghostbusters. It not Dr. Strangelove’s health blog. It’s a group called the Cochrane Collaboration.

The Cochrane Collaboration consists of 30,000 volunteer scientific experts from across the globe whose sole mission is to analyze the scientific literature and publish reviews of health claims so that health professionals, patients, and policy makers can make evidence-based choices about health interventions.

The Cochrane Collaboration reviews all the relevant studies on a topic, exclude those that are biased or weak, and make their recommendations based on only the strongest studies. Their reviews are considered the gold standard of evidence-based medicine.

If you are of a certain age, you may remember that TV commercial “When EF Hutton talks, people listen.” It is the same with the Cochrane Collaboration. When they talk, health professionals listen.

This week we will examine the Cochrane Collaboration’s review titled “Omega-3 Fatty Acid Addition During Pregnancy”.

How Was The Study Done?

For this analysis the Cochrane Collaboration reviewed 70 randomized controlled trials which compared the effect of added omega-3s on pregnancy outcomes with either a placebo or a diet no added omega-3s. These trials included almost 19,927 pregnant women.

In one sense, Cochrane reviews are what is called a “meta-analysis”, in which data from numerous studies are grouped together so that a statistically significant conclusion can be reached. However, Cochrane Collaboration reviews differ from most meta-analyses found in the scientific literature in a very significant way.

Many published meta-analyses simply report “statistically significant” conclusions. However, statistics can be misleading. As Mark Twain said: “There are lies. There are damn lies. And then there are statistics”.

The problem is that the authors of most meta-analyses group studies together without considering the quality of studies included in their analysis. This creates a “Garbage In – Garbage Out” effect. If the quality of individual studies is low, the quality of the meta-analysis will also be low. Simply put, the conclusions from some published meta-analyses are not worth the paper they are written on.

The Cochrane Collaboration also reports statistically significant conclusions from their meta-analyses. However, they also carefully consider the quality of each individual study in their analysis. They look at possible sources of bias. They look at the design and size of the studies. Finally, they ask whether the conclusions are consistent from one study to the next. They clearly define the quality of evidence that backs up each of their conclusions as follows:

High-quality evidence. Further research is unlikely to change their conclusion. This is generally reserved for conclusions backed by multiple high-quality studies that have all come to the same conclusion. These are the recommendations that are most often adopted into medical practice.

Moderate-quality evidence. This conclusion is likely to be true, but further research could have an impact on it.

Low-quality evidence. Further research is needed and could alter the conclusion. They are not judging whether the conclusion is true or false. They are simply saying more research is needed to reach a definite conclusion.

Omega-3s Reduce Preterm Births

Here are the conclusions that the Cochrane Collaboration said were supported by high-quality evidence:

Omega-3s reduce the risk of preterm births.

Omega-3s reduce the risk of low-birth-weight infants.

The authors concluded: “Omega-3 supplementation during pregnancy is an effective strategy for reducing the risk of preterm birth…More studies comparing omega-3s and placebo are not needed at this point.”

In other words, they are saying this conclusion is definite. Omega-3 supplementation should become part of the standard of medical care for pregnant women.

However, they did say that further studies were needed “…to establish if, and how, outcomes vary by different types of omega-3s, timing [stage of pregnancy], doses [of omega-3s], or by characteristics of women.”

That’s because these variables were not analyzed in the Cochrane study. Their review and meta-analysis included clinical trials:

Of women at low, moderate, and high risk of poor pregnancy outcomes.

With DHA alone, with EPA alone, and with a mixture of both.

Omega-3 doses that were low (˂ 500 mg/day), moderate (500-1,000 mg/day), and high (> 1,000 mg/day).

Do Omega-3s Make For A Healthy Pregnancy?

What about the effect of omega-3s on other pregnancy outcomes?

The conclusions the Cochrane Collaboration said were supported by moderate quality evidence included reductions in:

Perinatal death.

Admissions to the neonatal intensive care unit.

There was not enough high or moderate quality data to determine the effect of omega-3s on other pregnancy outcomes such as postnatal depression. More research is still needed in those areas. However, if you do receive any of these benefits from omega-3 supplementation, you can just consider them as side benefits.

What Does This Report Mean For You?

1) The proven effect of omega-3 supplementation on preterm births is significant because preterm births increase the risk of:

Visual impairment.
Developmental Delay.
Learning difficulties.

2) The likely effect of omega-3s on admission to neonatal intensive care units is significant because those units are very expensive.

3) The Cochrane study did not determine whether omega-3 supplementation was equally important for women at low, moderate, and high likelihood of poor pregnancy outcomes.

Therefore, omega-3 supplementation should be considered for all pregnant women.

4) The Cochrane study did not determine whether omega-3 supplementation was equally important during the first, second, or third trimester.

Therefore, omega-3 supplementation should be considered by all women of childbearing age who might become pregnant and throughout pregnancy.

5) The Cochrane study did not determine whether DHA, EPA, or a mixture of the two was most effective.

Therefore, your omega-3 supplement should probably contain both DHA and EPA. A group of experts recently recommended that adults consume at least 650 mg/day of omega-3s with ≥ 220 mg of that coming from DHA and ≥ 220 mg/day coming from EPA.

Since most pregnant women in this country consume around 89 mg/day of DHA + EPA, omega-3 supplementation is warranted.

The Bottom Line

The effect of omega-3s on pregnancy outcomes have been confusing. Some studies conclude that omega-3s are important for a healthy pregnancy. Other studies suggest they are ineffective. What are you to believe?

Fortunately, a group called the Cochrane Collaboration recently conducted a comprehensive review of this topic. This is significant because Cochrane Reviews are internationally recognized as the highest standard in evidence-based health care. They influence the treatment protocols recommended by the medical community.

This Cochrane Review concluded that omega-3 supplementation during pregnancy:

Reduces preterm births and low birth weight infants.

Likely reduces perinatal death and admissions to the neonatal intensive care unit.

The authors of the review said: “Omega-3 supplementation during pregnancy is an effective strategy for reducing the risk of preterm birth…More studies comparing omega-3s and placebo are not needed at this point.”

In other words, they are saying this conclusion is definite. Omega-3 supplementation should become part of the standard of medical care for pregnant women.

For more details on 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.

How Much Omega-3 Should You Take During Pregnancy?

June 22, 2021 by Dr. Steve Chaney

Which Omega-3s Are Beneficial?

Author: Dr. Stephen Chaney

Preterm births (births occurring before 37 weeks) are increasing in this country. Just between 2018 and 2019, the percentage of preterm births increased by 2% to over 10% of all pregnancies. That is a concern because preterm births are associated with an increased risk of:

Visual impairment.
Developmental delays.
Learning difficulties.
Problems with normal development of lungs, eyes, and other organs.

Plus, it is expensive to keep premature babies alive. One recent study estimated that reducing the incidence of preterm births by around 50% could reduce health care costs by $6 billion in the United Stated alone.

Of the 10% preterm births, 2.75% of them are early preterm births (births occurring before 34 weeks). Obviously, the risk of health problems and the cost of keeping them alive is greatest for early preterm babies.

We don’t know why preterm births are increasing, but some experts feel it is because in this country:

More older women are having babies.

There is increased use of fertility drugs, resulting in multiple babies

Unfortunately, there is no medical standard for identifying pregnancies at risk for preterm birth. Nor is there any agreement around prevention measures for preterm births.

However, recent research has suggested that some premature births may be caused by inadequate omega-3 status in the mother and can be prevented by omega-3 supplementation.

What Do We Know About Omega-3s And Risk Of Preterm Births?

The problem is that almost all these claims have been called into question by other studies. If you are pregnant or thinking of becoming pregnant, you don’t know what to believe.

Fortunately, a group called the Cochrane Collaboration has recently reviewed these studies. The Cochrane Collaboration consists of 30,000 volunteer scientific experts from across the globe whose sole mission is to analyze the scientific literature and publish reviews of health claims so that health professionals, patients, and policy makers can make evidence-based choices about health interventions. Their reviews are considered the gold standard of evidence-based medicine.

This is because most published meta-analyses simply report “statistically significant” conclusions. However, statistics can be misleading. As Mark Twain said: “There are lies. There are damn lies. And then there are statistics”.

The problem is the authors of most meta-analyses group studies together without considering the quality of studies included in their analysis. This creates a “Garbage In – Garbage Out” effect. If the quality of individual studies is low, the quality of the meta-analysis will also be low.

The Cochrane Collaboration reviews are different. They also report statistically significant conclusions from their meta-analyses. However, they carefully consider the quality of each individual study in their analysis. They look at possible sources of bias. They look at the design and size of the studies. Finally, they ask whether the conclusions are consistent from one study to the next. They clearly define the quality of evidence that backs up each of their conclusions.

For omega-3s and pregnancy, the Cochrane Collaboration performed a meta-analysis and review of 70 randomized controlled trials that compared the effect of added omega-3s on pregnancy outcomes with the effect of either a placebo or no omega-3s. These trials included almost 19,927 pregnant women.

This Cochrane Collaboration Review looked at all the claims for omega-3s and pregnancy outcome, but they concluded that only two of the claims were supported by high-quality evidence:

Omega-3s reduce the risk of preterm births.

Omega-3s reduce the risk of low birth-weight infants.

The authors concluded: “Omega-3 supplementation during pregnancy is an effective strategy for reducing the risk of preterm birth…More studies comparing [the effect of] omega-3s and placebo [on preterm births] are not needed at this point.”

In other words, they are saying this conclusion is definite. The Cochrane Collaboration has declared that omega-3 supplementation should become part of the standard of medical care for pregnant women.

However, the Cochrane Collaboration did say that further studies were needed “…to establish if, and how, outcomes vary by different types of omega-3s, timing [stage of pregnancy], doses [of omega-3s], or by characteristics of women.”

That’s because these variables were not analyzed in this study. The study included clinical trials:

Of women at low, moderate, and high risk of poor pregnancy outcomes.

With DHA alone, with EPA alone, and with a mixture of both.

Omega-3 doses that were low (˂ 500 mg/day), moderate (500-1,000 mg/day), and high (> 1,000 mg/day).

I have discussed these findings in more detail in a previous issue of “Health Tips From The Professor”

How Was This Study Done?

The current study (SE Carlson et al, EClinicalMedicine, 2021) is a first step towards answering those questions.

The authors of this study focused on how much DHA supplementation is optimal during pregnancy. This is an important question because there is currently great uncertainty about how much DHA is optimal:

The American College of Obstetrics and Gynecology recommends supplementation with 200 mg/day of DHA. However, that recommendation assumes that the increase will come from fish and was influenced by concerns that omega-3-rich fish are highly contaminated with heavy metals and PCBs.

Another group of experts was recently asked to develop guidelines for omega-3 supplementation during pregnancy. They recommended pregnant women consume at least 300 mg/day of DHA and 220 mg/day of EPA.

The WHO has recommended of minimum dose of 1,000 mg of DHA during pregnancy.

Many prenatal supplements now contain 200 mg of DHA, but very few provide more than 200 mg.

Accordingly, the authors took the highest and lowest recommendations for DHA supplementation and asked whether 1,000 mg of DHA per day was more effective than 200 mg of DHA at reducing the risk of early preterm births. Their hypothesis was that 1,000 mg of DHA would be more effective than 200 mg/day at preventing early preterm births.

This study was a multicenter, double-blind, randomized trial of 1032 women recruited at one of three large academic medical centers in the United States (University of Kansa, Ohio State University, and University of Cincinnati).

The women were ≥ 18 years old (average age = 30) and between 12 and 20 weeks of gestation when they entered the study.

The breakdown by ethnicity was 50% White, 22% Black or African American, 22% Hispanic, 6% Other.

18% had a prior preterm birth (<37 weeks) and 7% had a prior early preterm birth (<34 weeks).

Prior to enrollment in the study 47% of the participants reported taking a DHA supplement and 19% of the participants took a DHA supplement with > 200 mg/day.

All the participants received 200 mg DHA capsules and were told to take one capsule daily. The participants were also randomly assigned to take 2 additional capsules that contained a mixture of corn and soybean oil (the 200 mg DHA/day group) or 2 capsules that contained 400 mg of DHA (the 1,000 mg DHA/day group). The capsules were orange flavored so the participants could not distinguish between the DHA capsules and the placebo capsules.

Blood samples were drawn upon entry to the study and either just prior to delivery or the day after delivery to determine maternal DHA status.

The study was designed to look at the effect of DHA dose (1,000 mg or 200 mg) on early preterm birth (<34 weeks), preterm birth (<37 weeks), low birth weight (< 3 pounds), and several other parameters related to maternal and neonatal health.

How Much Omega-3 Should You Take During Pregnancy?

The primary findings from this study were:

The rate of early preterm births (<34 weeks) was less (1.7%) for pregnant women taking 1,000 mg of DHA/day compared to 200 mg/day (2.4%).

The rate of late preterm births (between 34 and 37 weeks) was also less for women taking 1,000 mg of DHA/day compared to 200 mg/day.

Finally, low birth weight and the frequency of several maternal and neonatal complications during pregnancy, delivery, and immediately after delivery were also lower with 1,000 mg/day of supplemental DHA than with 200 mg/day.

This confirms the authors’ hypothesis that supplementation with 1,000 mg/day of DHA is more effective than 200 mg/day at reducing the risk of early preterm births. In addition, this study showed that supplementation with 1,000 mg of DHA/day had additional benefits.

This study did not have a control group receiving no DHA. However:

The US average for early preterm births is 2.74%.

For the women in this study who had previous pregnancies, the rate of early preterm birth was 7%.

Of course, the important question for any study of this type is whether all the women benefited equally from supplementation. Fortunately, this study was designed to answer that question.

As noted above, each woman was asked whether they took any DHA supplements at the time they enrolled in the study, and 47% of the women in the study were taking DHA supplements when they enrolled. In addition, the DHA status of each participant was determined from blood samples taken at the time the women were enrolled in the study. When the authors split the women into groups based on their DHA status at the beginning of the study:

For women with low DHA status the rate of early preterm births was 2.0% at 1,000 mg of DHA/day versus 4.1% at 200 mg of DHA/day.

For women with high DHA status the rate of early preterm births was around 1% for both 1,000 mg of DHA/day and 200 mg of DHA/day.

In other words, DHA supplementation only appeared to help women with low DHA status. This is good news because:

DHA status is an easy to measure predictor of women who are at increased risk of early preterm birth.

This study shows that supplementation with 1,000 mg of DHA/day is effective at reducing the risk of early premature birth for women who are DHA deficient.

In the words of the authors, “Clinicians could consider prescribing 1,000 mg DHA daily during pregnancy to reduce early preterm birth in women with low DHA status if they are able to screen for DHA.”

Which Omega-3s Are Beneficial?

DHA is the most frequently recommended omega-3 supplement during pregnancy.

It is not difficult to understand why that is.

DHA is a major component of the myelin sheath that coats every neuron in the brain. [You can think of the myelin sheath as analogous to the plastic coating on a copper wire that allows it to transmit electricity from one end of the wire to the other.]

Unlike other components of the myelin sheath, the body cannot make DHA. It must be provided by the diet.

During the third trimester, DHA accumulates in the human brain faster than any other fatty acid.

Animal studies show that DHA deficiency during pregnancy interferes with normal brain and eye development.

Some, but not all, human clinical trials show that DHA supplementation during pregnancy improves developmental and cognitive outcomes in the newborn.

Recent studies have shown that most women in the United States only get 60-90 mg/day of DHA in their diet.

Clearly, DHA is important for fetal brain development during pregnancy, and most pregnant women are not getting enough DHA in their diet. This is why most experts recommend supplementation with DHA during pregnancy. And this study suggests supplementation with 1,000 mg/day is better than 200 mg/day. However, two important questions remain:

#1: Is 1,000 mg of DHA/day optimal? The answer is, “We don’t know”. This study compared the highest recommended dose (1,000 mg/day) with the lowest recommended dose (200mg/day) and concluded that 1,000 mg/day was better than 200 mg/day.

But would 500 or 800 mg/day be just as good as 1,000 mg/day? We don’t know. More studies are needed.

#2: Can DHA do it all, or are other omega-3s also important for a healthy pregnancy? As noted above, the emphasis on supplementation with DHA was based on the evidence for a role of DHA in fetal brain development during pregnancy.

But is DHA or EPA more effective at preventing early preterm birth and maternal pregnancy complications? Again, we don’t know.

As noted above, the Cochrane Collaboration concluded that omega-3s were effective at reducing early preterm births but was unable to evaluate the relative effectiveness of EPA and DHA because their review included studies with DHA only, EPA only, and EPA + DHA.

This is an important question because the ability of the body to convert EPA to DHA and vice versa is limited (in the 10-20%) range. This means that if both EPA and DHA are important for a healthy pregnancy, it might not be optimal to supplement with a pure DHA or pure EPA supplement.

Based on currently available data if you are pregnant or thinking of becoming pregnant, my recommendations are:

Chose a supplement that provides both EPA and DHA.

Because the evidence is strongest for DHA at this time, chose an algal source of omega-3s that has more DHA than EPA.

Aim for a dose of DHA in the 500 mg/day to 1,000 mg/day range. Remember, this study showed 1,000 mg/day was better than 200 mg/day but did not test whether 500 or 800 mg/day might have been just as good.

As more data become available, I will update my recommendations.

The Bottom Line

The Cochrane Collaboration recently released a report saying that the evidence was definitive that omega-3 supplementation during pregnancy reduced the risk of early preterm births. However, they were not able to reach a definitive conclusion on the optimal dose of omega-3s or the relative importance of EPA and DHA at preventing early preterm birth.

Most experts recommend that pregnant women supplement with between 200 mg/day and 1,000 mg/day of DHA.

A recent study asked whether 1,000 mg of DHA/day was better than 200 mg/day at reducing the risk of early preterm birth. The study found:

The rate of early preterm births (<34 weeks) was less (1.7%) for pregnant women taking 1,000 mg of DHA/day than pregnant women taking 200 mg/day (2.4%).

For women with low DHA status at the beginning of the study, the rate of early preterm births was 2.0% at 1,000 mg of DHA/day versus 4.1% at 200 mg of DHA/day.

For women with high DHA status at the beginning of the study, the rate of early preterm births was around 1% for both 1,000 mg of DHA/day and 200 mg of DHA/day.

The authors concluded, “Clinicians could consider prescribing 1,000 mg DHA daily during pregnancy to reduce early preterm birth in women with low DHA status…”

There are two important caveats:

This study did not establish the optimal dose of DHA. The study concluded that 1,000 mg/day was better than 200 mg/day. But would 500 or 800 mg/day be just as good as 1,000 mg/day? We don’t know. More studies are needed.

This study did not establish the relative importance of EPA and DHA for reducing the risk of early preterm births. DHA is recommended for pregnant women based on its importance for fetal brain development. But is DHA more important than EPA for reducing the risk of early preterm births? Again, we don’t know. More studies are needed.

For more details about this study and my recommendations, read the article above.

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

Do Omega-3s Add Years To Your Life?

June 1, 2021 by Dr. Steve Chaney

Why Are Omega-3s So Controversial?

Author: Dr. Stephen Chaney

I don’t need to tell you that omega-3s are controversial. Some experts confidently tell you that omega-3s significantly reduce your risk of heart disease and may reduce your risk of cancer and other diseases. Other experts confidently tell you that omega-3s have no effect on heart disease or any other disease. They claim that omega-3 supplements are no better than “snake oil”.

The problem is that each camp of experts can cite published clinical studies to support their claims. How can that be? How can clinical studies come to opposite conclusions on such an important topic? The problem is that it is really difficult to do high quality clinical studies on omega-3s. I will discuss that in the next section.

The question of whether omega-3s affect life span has also been controversial. Heart disease and cancer are the top two causes of death in this country. So, if omega-3s actually reduced the risk of heart disease and cancer, you might expect that they would also help us live longer. Once again, there are studies on both sides of this issue, but they are poor quality studies.

We need more high-quality studies to clear up the controversies surrounding the health benefits of omega-3s. I will report on one such study in this issue of “Health Tips From The Professor”. But first let me go into more depth about why it is so difficult to do high-quality studies with omega-3 fatty acids.

Clinical Studies 101: Why Are Omega-3s So Controversial?

I have covered this topic in previous issues of “Health Tips From the Professor”, but here is a quick summary.

Randomized, placebo controlled clinical trials (RCTs) are considered the gold standard for evidence-based medicine, but they ill-suited to measure the effect of omega-3s on health outcomes.

- Heart disease and cancer take decades to develop. Most RCTs are too small and too short to show a meaningful effect of omega-3s on these diseases.

- To make up for this shortcoming, some recent RCTs have started with older, sicker patients. This way enough patients die during the study that it can measure statistically significant outcomes. However, these patients are already on multiple medications that mimic many of the beneficial effects of omega-3s on heart disease.

These studies are no longer asking whether omega-3s reduce the risk of heart disease. They are really asking if omega-3s have any additional benefits for patients who are already taking multiple medications – with all their side effects. I don’t know about you, but that is not the question I am interested in.

- Until recently, most RCTs did not measure circulating omega-3 levels before and after supplementation, so the investigators had no idea whether omega-3 supplementation increased circulating omega-3 levels by a significant amount.

And for the few studies where omega-3 levels were measured before and after supplementation, it turns out that for many of the participants, their baseline omega-3 levels were too high for omega-3 supplementation to have a meaningful effect. Only participants with low omega-3 levels at the beginning of the study benefited from omega-3 supplementation.

These studies are often quoted as showing omega-3 supplementation doesn’t work. However, they are actually showing the true value of supplementation. Omega-3 supplementation isn’t for everyone. It is for people with poor diet, increased need, genetic predisposition, and/or pre-existing disease not already treated with multiple medications.

2) Prospective cohort studies eliminate many of the shortcomings of RCTs. They can start with a large group of individuals (a cohort) and follow them for many years to see how many of them die or develop a disease during that time (this is the prospective part of a prospective cohort trial). This means they can start with a healthy population that is not on medications.

This also means that these studies can answer the question on most people’s minds, “Are omega-3s associated with reduced risk of dying or developing heart disease?” However, these studies have two limitations.

- They are association studies. They cannot measure cause and effect.

- Ideally, omega-3 levels would be measured at the beginning of the study and at several intervals during the study to see if the participant’s diet had changed during the study. Unfortunately, most prospective cohort studies only measure omega-3 levels at the beginning of the study.

3) Finally, a meta-analysis combines data from multiple clinical studies.

- The strength of a meta-analysis is that the number of participants is quite large. This increases the statistical power and allows it to accurately assess small effects.

- The greatest weakness of meta-analyses is that the design of the individual studies included in the meta-analysis is often quite different. This introduces variations that decrease the reliability of the meta-analysis. It becomes a situation of “Garbage in. Garbage out”

The study (WS Harris et al, Nature Communications, Volume 12, Article number: 2329, 2021) I am discussing today is a meta-analysis of prospective cohort studies. It was designed to determine the association between blood omega-3 fatty acids and the risk of:

Death from all causes.
Death from heart disease.
Death from cancer.
Death from causes other than heart disease or cancer.

More importantly, it eliminated the major weakness of previous meta-analyses by only including studies with a similar design.

How Was This Study Done?

This study was a meta-analysis of 17 prospective cohort studies with a total of 42,466 individuals looking at the association between omega-3 fatty acid levels in the blood and premature death due to all causes, heart disease, cancer, and causes other than heart disease and cancer.

Participants in the 17 studies were followed for an average of 16 years, during which time 15,720 deaths occurred. This was a large enough number of deaths so that a very precise statistical analysis of the data could be performed.

The average age of participants at entry into the studies was 65, and 55% of the participants were women. Whites constituted 87% of the participants, so the results may not be applicable to other ethnic groups. None of the participants had heart disease or cancer when they entered the study.

Finally, the associations were corrected for a long list of variables that could have influenced the outcome (Read the publication for more details).

A strength of this meta-analysis is that all 17 studies were conducted as part of the FORCE (Fatty Acids & Outcomes Research Consortium) collaboration. The FORCE collaboration was established with the goal of understanding the relationships between fatty acids (as measured by blood levels of the omega-3 fatty acids) on premature death and chronic disease outcomes (cardiovascular disease, cancer, and other conditions).

Each study was designed using a standardized protocol, so that the data could be easily pooled for a meta-analysis. In the words of the FORCE collaboration founders:

The larger sample sizes of [meta-analyses] will substantially increase statistical power to investigate associations…enabling the [meta-analyses] to discover important relationships not discernible in any individual study.

2) Standardization of variable definitions and modeling of associations will reduce variation and potential bias in estimates across cohorts.

3) Results will be far less susceptible to publication bias.

Do Omega-3s Add Years To Your Life?

The meta-analysis divided participants into quintiles based on blood omega-3 levels. When comparing participants with the highest omega-3 levels with participants with the lowest omega-3 levels:

Premature death from all causes was decreased by 16%.

- When looking at the effect of individual omega-3s, EPA > EPA+DHA > DHA.

Premature death from heart disease was decreased by 19%.

- When looking at the effect of individual omega-3s, DHA > EPA+DHA > EPA.

Premature death from cancer was decreased by 15%.

- When looking at the effect of individual omega-3s, EPA > DHA > EPA+DHA.

Premature death from causes other than heart disease and cancer was decreased by 18%.

- When looking at the effect of individual omega-3s, EPA > EPA+DHA > DHA.

The differences between the effects of EPA, DHA, and EPA+DHA were small.

ALA, a short chain omega-3 found in plant foods, had no effect on any of these parameters.

In the words of the authors: “These findings suggest that higher circulating levels of long chain omega-3 fatty acids are associated with a lower risk of premature death. Similar relationships were seen for death from heart disease, cancer, and causes other than heart disease and cancer. No associations were seen with the short chain omega-3, ALA [which is found in plant foods]”.

What Does This Study Mean For You?

If you are thinking that 15-19% decreases in premature death from various causes don’t sound like much, let me do some simple calculations for you. The average lifespan in this country is 78 years.

A 16% decrease in death from all causes amounts to an extra 12.5 years. What would you do with an extra 12.5 years?

A 19% decrease in death from heart disease might not only allow you to live longer, but it has the potential to improve your quality of life by living an extra 15 years free of heart disease.

Similarly, a 15% decrease in death from cancer might help you live an extra 12 years cancer-free.

In other words, you may live longer, and you may also live healthier longer, sometimes referred to as “healthspan”.

Don’t misunderstand me. Omega-3s are not a magic wand. They aren’t the fictional “Fountain of Youth”.

There are many other factors that go into a healthy lifestyle. If you sit on your couch all day eating Big Macs and drinking beer, you may be adding the +12.5 years to a baseline of -30 years.

Clinical studies report average values and none of us are average. Omega-3s will help some people more than others.

I will understand if you are skeptical. It seems like every time one study comes along and tells you that omega-3s are beneficial, another study comes along and tells you they are worthless.

This was an extraordinarily well-designed study, but it is unlikely to be the final word in the omega-3 controversy. There are too many poor-quality studies published each year. Until everyone in the field agrees to some common standards like those in the FORCE collaboration, the omega-3 controversy will continue.

The Bottom Line

A recent meta-analysis looked at the association between omega-3 fatty acid levels in the blood and premature death due to all causes, heart disease, cancer, and causes other than heart disease and cancer.

The meta-analysis divided participants into quintiles based on blood omega-3 levels. When comparing participants with the highest omega-3 levels with participants with the lowest omega-3 levels:

Premature death from all causes was decreased by 16%.

Premature death from heart disease was decreased by 19%.

Premature death from cancer was decreased by 15%.

Premature death from causes other than heart disease and cancer was decreased by 18%.

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

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

Update On Omega-3 Supplementation And Heart Disease

November 10, 2020 by Dr. Steve Chaney

How Much Omega-3s Do You Need?

In previous issues of “Health Tips From The Professor” I have described the medical consensus about omega-3 supplementation and heart disease as resembling a pendulum.

A few positive studies are published, and the pendulum swings in the positive direction. The medical consensus becomes, “Omega-3s may reduce heart disease risk.”

Then a few negative studies are published, and the pendulum swings in the other direction. The consensus becomes that omega-3 supplements are worthless. One review a few years ago went so far as to say that fish oil supplements were the modern-day version of snake oil.

Meta-analyses combine the data from multiple clinical studies to increase statistic power and minimize the effect of clinical studies that are outliers. They are supposed to provide clear answers to medical questions like the effect of omega-3 supplements on heart disease.

However, the meta-analyses published to date have also reached conflicting conclusions about the effectiveness of omega-3 supplementation. No wonder you [and the medical community] are confused!

In 2018 three large, well-designed, clinical studies looking at the effect of omega-3 supplementation on heart disease risk were published. They reached different conclusions. However, they covered a much wider range of omega-3 doses than previous studies. And the studies with the highest doses of omega-3s showed the most positive effect of omega-3 supplementation on the reduction of heart disease risk.

That lead a group of doctors and scientists from the United States and Finland to postulate that many previous studies had failed to find an effect of omega-3 supplements on heart disease risk because the dose of omega-3s they used was too low.

These scientists designed a very large meta-analysis (AA Bernasconi et al, Mayo Clinic Proceedings, doi.org/10.1016/j.mayocp.2020.08.034) to test their hypothesis. In short, their study was designed to:

Determine whether supplementation with the omega-3 fatty acids EPA and DHA resulted in reduced heart disease risk.

Quantify the relationship between the dose of EPA + DHA and the risk of heart disease outcomes.

How Was The Study Done?

This study was a meta-analysis of 40 randomized control clinical studies on the effect omega-3 supplementation on heart disease outcomes. Specifically:

It included all high-quality clinical studies of omega-3 supplementation published before August 2019.

It included a total of 135,267 participants.

It included participants at both low and high risk of developing heart disease.

It included studies of supplementation with EPA alone and with EPA + DHA.

It included omega-3 doses ranging from 400 mg/day to 5,500 mg/day.

It excluded dietary studies because:

- It is difficult to measure the dosage of omega-3s that participants are consuming in dietary studies.

- It is difficult to assure their compliance with dietary advice.

- There is variation in the omega-3 content of various foods.

- Participants in these studies are often advised to make other changes in diet. It then becomes difficult to know whether any benefits observed were from changes in omega-3s or from changes in other components of the diet.

Update On Omega-3 Supplementation And Heart Disease

Here are the results of the meta-analysis. Supplementation with EPA or EPA + DHA reduced:

Coronary Heart disease (defined as diseases caused by atherosclerosis, such as angina, heart attack, and heart failure) by 10%.

Heart Attacks by 13%.

Coronary Heart disease deaths by 9%.

Heart attack deaths by 35%.

Because of the large number of participants in this meta-analysis, they were able to reach some other important conclusions:

Despite the claims you may have heard about a new drug consisting of highly purified EPA, this study found no evidence that EPA supplementation was superior to EPA + DHA supplementation.

Even though heart medications provide some of the same benefits as omega-3s, this study concluded that omega-3 supplementation reduced the risk of heart disease even for patients on multiple heart medications.

This study also concluded that omega-3 supplementation was likely to be effective for people at both low and high risk of heart disease. This means that omega-3 supplementation is likely to be beneficial for preventing heart disease.

The authors concluded: “The current study provides strong evidence that EPA + DHA supplementation is an effective strategy for the prevention of certain coronary heart disease outcomes…Considering the relatively low costs and side effect profiles of omega-3 supplementation and the low drug-drug interactions with other standard therapies…clinicians and patients should consider the potential benefits of omega-3 (EPA/DHA) supplementation…”

What Does This Study Mean For You?

The most significant conclusions from this study are the reduction in heart attacks and heart attack deaths. That is because:

Approximately 1.5 million Americans suffer a heart attack each year. For those who survive their quality of life may be permanently altered.

- A 13% reduction in heart attacks means that something as simple as EPA + DHA supplementation might prevent as many as 195,000 heart attacks a year.

Approximately 100,000 Americans will die from a heart attack each you.

- A 35% reduction in heart attack deaths means that EPA + DHA supplementation might prevent as many as 35,000 deaths from heart attacks each year.

For many Americans sudden death from a heart attack is the first indication that they have heart disease.

- As Benjamin Franklin said, “An ounce of prevention is worth a pound of cure”. That is why EPA + DHA supplementation makes sense for most people.

I can’t say that this study will be the final word on omega-3 supplementation and heart disease risk. However, several recent studies have supported the benefit of omega-3 supplementation at reducing heart disease risk. The pendulum has clearly swung in the direction of omega-3s being beneficial for heart health.

Of course, omega-3 supplementation is not a magic “Get Out of Jail Free” card. You can’t expect it to overcome the effects of a bad diet and lack of exercise with omega-3 supplementation alone. You need a holistic approach.

The American Heart Association recommends:

If you smoke, stop.

Choose good nutrition.

- Choose a diet that emphasizes vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, non-tropical vegetable oils, and nuts.

- Choose a diet that limits sweets, sugar-sweetened beverages, and red meats.

Reduce high blood cholesterol and triglycerides.

Reduce your intake of saturated fat, trans fat and cholesterol and get moving.

Lower High Blood Pressure.

Be physically active every day.

- Aim for at least 150 minutes per week of moderate-intensity physical activity per week.

Aim for a healthy weight.

Manage diabetes.

Reduce stress.

Limit alcohol.

Have a regular physical checkup.

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

How Much Omega-3s Do You Need?

As I mentioned at the beginning of this article the omega-3 dosages used in the studies included in this meta-analysis ranged from 400 mg/day to 5,500 mg/day. More importantly, there were enough participants in these studies to obtain a fairly accurate estimate of dose response. This allow the authors to answer the question, “How much omega-3s do I need?”The study found that:

The protective effect of omega-3s for heart attack deaths and coronary heart disease deaths plateaued with dosages of EPA + DHA that exceeded 800 – 1200 mg/day.

The dose response of the protective effect of omega-3s for non-fatal heart attacks was linear over a wider range of dosages, with every increase 1,000 mg/day of EPA + DHA decreasing the risk of heart attack by 9%.

Based on the totality of their data, the authors concluded, “…clinicians and patients should consider the potential benefits of omega-3 supplementation, especially using 1,000 to 2,000 mg/day dosages, which are rarely obtained in most Westernized diets, even those including routine fish consumption.”

The Bottom Line

A recent meta-analysis combined the data from 40 clinical studies with over 135,000 participants looking at the effect of omega-3 supplementation on various types of heart disease. The study found that supplementation with EPA or EPA + DHA reduced:

Coronary Heart disease (defined as diseases caused by atherosclerosis, such as angina, heart attack, and heart failure) by 10%.

Heart Attacks by 13%.

Coronary Heart disease deaths by 9%.

Heart attack deaths by 35%.

Because of the large number of participants in this meta-analysis, they were able to reach some other important conclusions:

This study found no evidence that EPA supplementation was superior to EPA + DHA supplementation.

This study concluded that omega-3 supplementation reduced the risk of heart disease even for patients on multiple heart medications.

This study also concluded that omega-3 supplementation was likely to be effective for people at both low and high risk of heart disease. This means that omega-3 supplementation is likely to be beneficial for preventing heart disease.

The optimal dose of EPA + DHA appeared to be 1,000 – 2,000 mg/day.

The authors of the study concluded: “The current study provides strong evidence that EPA + DHA supplementation is an effective strategy for the prevention of certain coronary heart disease outcomes…Considering the relatively low costs and side effect profiles of omega-3 supplementation and the low drug-drug interactions with other standard therapies…clinicians and patients should consider the potential benefits of omega-3 (EPA/DHA) supplementation, especially using 1,000 to 2,000 mg/day dosages, which are rarely obtained in most Westernized diets, even those including routine fish consumption.”

For more details, including a more detailed discussion of what this study means for you, read the article above.

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

How Much DHA Is Needed To Prevent Alzheimer’s

September 8, 2020 by Dr. Steve Chaney

What Are We Missing?

We are an aging population. As such, issues like cognitive decline, dementia, and Alzheimer’s Disease are of increasing concern. After all, what is the good of reaching your “Golden Years” with a healthy body if you lose your mind?

The ability of the omega-3 fatty acids DHA and EPA to reduce the risk of cognitive decline, dementia, and Alzheimer’s Disease is controversial. Some studies say yes. Others say no.

When studies are conflicting most experts simply conclude the treatment is unproven. I am sympathetic to that viewpoint, but I first like to ask the questions: “Why are the studies conflicting? What are we missing?”

I start by evaluating the strengths and weaknesses of the individual studies.

If the studies claiming the treatment works are weak, I am content to “join the chorus” and consider the treatment unproven.

If the studies claiming the treatment doesn’t work are weak, I am a strong advocate for more well-designed studies before we conclude that the treatment doesn’t work.

If both the “pro” and “con” studies are strong, I want to ask, “What are we missing?”

This is the situation with studies asking whether DHA reduces the risk of Alzheimer’s Disease and other forms of cognitive decline as we age.

Association studies show that greater intake and higher blood levels of the omega-3 fatty acids EPA and DHA are associated with lower risk of Alzheimer’s Disease.

However, most placebo-controlled clinical trials with either DHA alone or DHA + EPA have come up negative. Of course, one can always argue that most of the placebo-controlled clinical trials were too short or too small to show a statistically significant effect. But, my question remains, “What else are we missing?”

One recent study has provided an interesting clue. The authors of the study postulated that B vitamins were required to deliver omega-3 fatty acids to the brain, and their study showed that omega-3 fatty acids were only effective at decreasing the risk of cognitive decline in subjects who also had optimal B vitamin status.

In other words, this study suggested that studies on the effect of omega-3 supplementation and risk of developing Alzheimer’s are doomed to failure if a significant percentage of the subjects have sub-optimal B vitamin status.

The authors of the current study ( IC Arellanes et al, EBioMedicine, doi.org/10.1016/j.ebiom.2020.102883) proposed two additional hypotheses for the negative results of previous clinical trials and designed an experiment to test their hypotheses. Their hypotheses were:

Uptake of DHA and EPA by the brain is very inefficient, and previous studies have not used sufficient doses of DHA or DHA plus EPA to see a significant effect on cognitive impairment.

The APOE4 gene further decreases the uptake of DHA and EPA by the brain.

Before I describe how the study was done, I should probably provide some context by describing how DHA and EPA reach the brain and the role of the apoE protein in the process. It’s time for my favorite topic: “Biochemistry 101”.

Biochemistry 101: What Does The ApoE Protein Do?

If you have ever tried to mix oil and water, it should come as no surprise to you that fats, including DHA and EPA, and cholesterol are not water soluble. That leaves our bodies with a dilemma. How do they get the fat and cholesterol we eat to pass through our bloodstream and get to our cells, where they are needed?

Our body’s solution is to incorporate the fat and cholesterol into particles called lipoproteins. Lipoprotein particles sequester the fat and cholesterol in their interior and surround them with water soluble phospholipids and proteins. Lipoproteins allow our bodies to transport fat and cholesterol through our bloodstream to the tissues that need them.

The next question, of course, is how the lipoproteins know which cells need the fat and cholesterol. This is where apoproteins like apoE come into play. We can think of the apoE protein as a zip code that directs lipoproteins to cells with an apoE receptor.

Our nervous system contains lots of apoE receptors, and binding of the apoE protein to its receptor is instrumental in the delivery of DHA, EPA, and cholesterol to our nervous system.

DHA and cholesterol are both important for brain health. That is because they are major components of the myelin sheath that wraps around our neurons and protects them. EPA may also be important for brain health because its anti-inflammatory effects are thought to prevent the accumulation of the amyloid plaques that are the hallmark of late-onset Alzheimer’s Disease.

There are three major versions of the APOE gene, APOE2, APOE3, and APOE4. Each of them plays slightly different roles in our body. However, it is the APOE4 version that is of interest to us. About 25% of us have the APOE4 version of the APOE gene and it increases our risk of developing Alzheimer’s Disease by a factor of two.

We do not know why this is, but one hypothesis is that lipoproteins with the apoE4 protein have more difficultly delivering much needed DHA, EPA, and cholesterol to the brain. This is one of the hypotheses that the authors set out to study.

How Was The Study Done?

There are two things you should know about this study.

This was a pilot study designed to test the author’s hypotheses and allow them to choose the correct dose of DHA to use for a subsequent study designed to test whether high-dose DHA can reduce the risk of developing Alzheimer’s Disease.

This was a very small study. That’s because the only way to determine how much DHA and EPA reaches the nervous tissue is to perform a lumbar puncture and obtain cerebrospinal fluid at baseline and again at the end of the study. Lumbar punctures are both painful and a bit risky. They were lucky to find 26 individuals who consented to the lumbar punctures.

This was a double-blind, placebo controlled clinical study.

Half the subjects were given 2,152 mg/day of DHA for 6 months, and half were given a daily placebo consisting of corn and soybean oil for 6 months.

Because previous studies have suggested that B vitamins were important for DHA and EPA uptake by nervous tissue, all subjects received a B vitamin supplement.

Levels of DHA and EPA were measured in both plasma and cerebrospinal fluid at baseline and again at the end of 6 months. Note: The subjects were only supplemented with DHA. The investigators were relying on the body’s ability to convert DHA into EPA.

All subjects were screened for APOE4

Other important characteristics of the study subjects were:

Average age was 69. They were 80% female.

All of them had a close family member who had previously been diagnosed with dementia, but none of them had been diagnosed with cognitive impairment at the time of entry into the study.

Around 45% of them had the APOE4 version of the APOE.

In other words, none of them currently had dementia, but most were at high risk of developing dementia.

How Much DHA Is Needed To Prevent Alzheimer’s?

After 6 months of supplementing with over 2,000 mg/day of DHA:

DHA levels in the blood had increased by 200%.

However, DHA levels in cerebrospinal fluid had increased by only 28%.

Moreover, DHA levels in cerebrospinal fluid were 40% lower in subjects who had the APOE4 gene compared to subjects with the APOE2 and APOE3

EPA levels in cerebrospinal fluid averaged about 15-fold lower than DHA levels. When they looked at the effect of DHA supplementation on EPA levels.

EPA levels in plasma had increased by 50%.

EPA levels in cerebrospinal fluid had increased by 43%.

EPA levels in cerebrospinal fluid were 3-fold lower in subjects who had the APOE4 gene compared to subjects with the APOE2 and APOE3

The authors concluded:

“We observed only a modest (28%) increase in cerebrospinal fluid DHA levels with 2152 mg per day of DHA supplementation. This finding has implications for past clinical trials that have used lower doses (e.g. 1 g daily of DHA supplements or less) and were overwhelmingly negative. Using lower doses of omega-3 supplements may have resulted in limited omega-3 brain delivery.”

“Another aspect affecting the response to DHA supplementation is APOE4 status. Subjects with the APOE4 gene showed lower DHA levels and significantly lower EPA levels than subjects with other APOE genes”.

“In summary, our study suggests that higher doses of omega-3 fatty acids (2 or more g of DHA) are needed to ensure adequate brain delivery, particularly in APOE4 carriers…Past low dose (1 g per day or less) omega-3 supplementation trials in dementia prevention may not have provided adequate brain levels to fully evaluate the efficacy of omega-3 supplementation on cognitive outcomes.”

Based on the results from this study the authors are currently testing the effect of B vitamins and high dose DHA supplementation on cerebrospinal fluid fatty acid levels, brain imaging, and cognitive outcomes in a larger ongoing clinical trial.

What Does This Study Mean For You?

The ability of the omega-3 fatty acids DHA and EPA to reduce the risk of cognitive decline, dementia, and Alzheimer’s Disease is confusing. Studies disagree.

In situations like this, most experts dismiss the hypothesis as “unproven”. However, I like to ask, “What are we missing?”

One recent study provided a clue. It suggested that omega-3s and B vitamins were interdependent. We need both to reduce cognitive decline. However, that might not be the complete answer.

This study gave both DHA and B vitamins to subjects and discovered another interesting clue. The study suggests we may not have been giving subjects enough omega-3s to see a significant effect on cognitive decline.

Let me start by saying this study did not test whether or not DHA supplementation prevents cognitive decline, dementia, and Alzheimer’s Disease. Nor does it tell us how much DHA is needed to prevent Alzheimer’s Disease, other than to show that anything less than 2 g per day is likely to be inadequate.

However, the study did make two important advances:

#1: It showed just how difficult it is to deliver adequate amounts of DHA and EPA to the brain. This is important because it shows:

Most previous studies have not used high enough doses of DHA or DHA plus EPA to evaluate the effect of omega-3 fatty acids on cognitive decline. Those studies were not simply negative. They were doomed to failure. The studies were worthless.

That means we should stop saying that the ability of omega-3s to prevent cognitive decline and diseases like Alzheimer’s is unproven. Instead, we should say that hypothesis has not adequately been tested.

That also means future studies of the ability of DHA to reduce the risk of cognitive decline, dementia, and/or Alzheimer’s will need to use much higher doses or a better delivery system to get adequate amounts of DHA and EPA into the brain.

#2: It showed that the APOE4 gene significantly decreases the ability of the brain to accumulate DHA and EPA. This has several important implications.

Because both DHA and EPA are vital for brain health, this may explain why the APOE4 gene increases the risk of Alzheimer’s Disease.

It also means those at highest risk for Alzheimer’s Disease are the ones who are most likely to have difficulties accumulating DHA and EPA in their brain.

Once again, it means future studies of the ability of supplemental DHA to reduce the risk of Alzheimer’s Disease will need to use much higher doses of DHA.

The Bottom Line

The ability of the omega-3 fatty acids DHA and EPA to reduce the risk of cognitive decline, dementia, and Alzheimer’s Disease is controversial.

Association studies show that greater intake and higher blood levels of the omega-3 fatty acids EPA and DHA are associated with lower risk of Alzheimer’s Disease.

However, most placebo-controlled clinical trials with either DHA alone or DHA + EPA have come up negative.

In situations like this, most experts dismiss the hypothesis as “unproven”. However, I like to ask, “What are we missing?”

One recent study provided a clue. It suggested that omega-3s and B vitamins were interdependent. We need optimal amounts of both to reduce dementia. However, that might not be the complete answer.

This study gave both DHA and B vitamins to participants and discovered another interesting clue. The study suggests we may not have been giving subjects enough omega-3s to see a significant effect on cognitive decline.

The authors of the study hypothesized:

Uptake of DHA and EPA by the brain is very inefficient, and previous studies have not used sufficient doses of DHA or DHA plus EPA to see a significant effect on cognitive impairment.

The APOE4 gene, which is known to increase the risk of Alzheimer’s Disease, further decreases the uptake of DHA and EPA by the brain.

Their study confirmed their hypotheses and made two important advancements:

#1: It showed just how difficult it is to deliver adequate amounts of DHA and EPA to the brain. This is important because it shows:

Most previous studies have not used high enough doses of DHA or DHA plus EPA to evaluate the effect of omega-3 fatty acids on cognitive decline. Those studies were not simply negative. They were doomed to failure. The studies were worthless.

That means we should stop saying that the ability of omega-3s to prevent cognitive decline and diseases like Alzheimer’s is unproven. Instead, we should say that hypothesis has not adequately been tested.

That also means future studies of the ability of DHA to reduce the risk of cognitive decline, dementia, and/or Alzheimer’s will need to use much higher doses or a better delivery system to get adequate amounts of DHA and EPA into the brain.

#2: It showed that the APOE4 gene significantly decreases the ability of the brain to accumulate DHA and EPA. This has several important implications.

Because both DHA and EPA are vital for brain health, this may explain why the APOE4 gene increases the risk of Alzheimer’s Disease.

It also means those at highest risk for Alzheimer’s Disease are the ones who are most likely to have difficulties accumulating DHA and EPA in their brain.

Once again, it means future studies of the ability of supplemental DHA to reduce the risk of Alzheimer’s Disease will need to use much higher doses of DHA.

Based on the results from this study the authors are currently testing the effect of B vitamins and high dose DHA supplementation on DHA and EPA levels in the brain, brain imaging, and cognitive outcomes in a larger ongoing clinical trial.

For more details, read the article above. For a better understanding of the roles of DHA, EPA, and the APOE gene in brain health, you may want to read my “Biochemistry 101” section 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.