Do Omega-3s Reduce Cognitive Decline?

October 31, 2023 by Dr. Steve Chaney

Should You Supplement With Omega-3s?

Author: Dr. Stephen Chaney

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

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

DHA is an essential part of the membrane that coats our neurons. As such, it is a major component of our brains and plays an important role in its structural integrity.

While EPA is not found in the brain it reduces inflammation and improves blood flow to the brain, both of which are important for brain health.

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

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

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

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

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

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

Because omega-3’s beneficial effects are widely publicized, many people are already consuming adequate amounts of omega-3s. A supplement study that does not measure the omega-3 status of participants at the beginning of the study and does not focus on participants with inadequate omega-3 status is doomed to failure.

Omega-3s may benefit older people more than younger people. A study that is not large enough to measure the effect of omega-3s on both groups is doomed to failure.

The APOE ɛ4 genotype is associated with an increased risk of cognitive decline and Alzheimer’s. Some studies suggest omega-3s are more beneficial for people with the APOE ɛ4 genotype, while other studies come to the opposite conclusion. This is a critical variable that needs to be resolved.

The ability of DHA to cross the blood-brain barrier and accumulate in our brain may be influenced by our genetics, especially our APOE ɛ4 status, and adequate levels of other nutrients, especially B vitamins. Unless studies are large enough to separate out these variables, they are doomed to failure. This study suggests accumulation of DHA in the brain is a critical variable that needs to be resolved.

Multiple studies suggest that higher doses of omega-3s are more effective at reducing cognitive decline than low doses of omega-3s. This study confirms that effect and identifies a threshold dose that is needed to provide measurable benefits. Studies providing supplemental omega-3s at doses below that threshold are likely to fail. And meta-analyses that combine low dose studies with high dose studies are also likely to come up empty.

Finally, people who take omega-3s for years are likely to benefit more than those who take omega-3s for just a few months. Again, this study confirms that effect, which means that studies involving short-term supplementation with omega-3s are likely to fail. And meta-analyses that combine short-term and long-term studies are likely to come up empty.

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

How Was This Study Done?

This study consisted of two parts:

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

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

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

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

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

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

Measured the relationship of omega-3 intake with the risk of Alzheimer’s Disease, all-cause dementia, or cognitive decline.

Were cohort studies (studies that follow a group of people over time) or case control studies (studies that compare people who develop a disease with those who do not).

Provided risk estimates or data that could be used to calculate risk.

Were original publications, not reviews or meta-analyses.

Do Omega-3s Reduce Cognitive Decline?

The results from Part 1 (data from the ADNI study) were as follows:

Omega-3 supplement users had a 37% lower risk of developing Alzheimer’s Disease than non-users.

Long-term (>10 years) omega-3 supplement users fared even better. They had a 64% lower risk of developing Alzheimer’s Disease than non-users.

When they broke the results for long-term omega-3 supplement users into subgroups:

- Males (67% risk reduction) benefitted more than females (50% risk reduction).

- People over 65 (65% risk reduction) benefited more than those under 65 (22% risk reduction).

- People with the APOE ɛ4 genotype (71% risk reduction) benefitted more than those who were APOE ɛ4 negative (55% risk reduction).

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

Dietary omega-3 intake lowered the risk of cognitive decline by 9%.

- People with the APOE ɛ4 genotype fared better (17% risk reduction).

- Their data suggested that a threshold of 1 gm/day omega-3s was needed before significant risk reduction was seen.

Dietary DHA intake lowered the risk of dementia by 27% and Alzheimer’s Disease by 24%.

Each 100 mg/day increase in DHA and EPA was associated with a significant reduction in the risk of cognitive decline (8% for DHA and 9.9% for EPA).

The authors concluded that,

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

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

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

Should You Supplement With Omega-3s?

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

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

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

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

The Bottom Line

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

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

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

Omega-3 supplement users had a 37% lower risk of developing Alzheimer’s Disease than non-users.

Long-term (>10 years) omega-3 supplement users fared even better. They had a 64% lower risk of developing Alzheimer’s Disease than non-users.

Dietary DHA intake lowered the risk of dementia by 27% and Alzheimer’s Disease by 24%.

Each 100 mg/day increase in DHA and EPA was associated with a significant reduction in the risk of cognitive decline (8% for DHA and 9.9% for EPA).

The threshold for observing a significant effect of omega-3s on cognitive decline was around 1 gram/day.

For more information on this study read the article above.

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

___________________________________________________________________________

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

Does Hormone Replacement Therapy Cause Dementia?

October 24, 2023 by Dr. Steve Chaney

The Dark Side Of Hormone Replacement Therapy

Author: Dr. Stephen Chaney

When I was still teaching, a physician and I were co-directors of one of the first courses medical students took at UNC. In his opening lecture to these brand-new medical students, one of his pearls of wisdom was the statement, “The only safe drug is a new drug.”

After a pause to let the students think about it, he followed up with, “That’s because the side effects haven’t been discovered yet.”

He would then go on to explain that every drug must go through rigorous clinical trials, and some side effects are discovered then. But some of the most serious side effects aren’t discovered until years later after 100’s of thousands of patients had used the drugs.

Hormone replacement therapy is a perfect example of this principle. Hormone replacement therapy was first introduced in the 1960s. At first it seemed to be an almost miraculous solution to menopausal symptoms.

Millions of women were overjoyed. After all, menopause symptoms can make life miserable. They include:

Hot flashes
Night sweats
Sleep disturbances
Mood swings
Depression
Anxiety
Forgetfulness
Food cravings
Tiredness

Just to name a few. While only 25% of women experience severe symptoms, why would anyone want to experience any of these symptoms?

And doctors were only too happy to oblige. Why not? The known side effects were mild. Why should any woman experience menopause symptoms?

But that was before the dark side of hormone replacement therapy started to emerge.

The Dark Side Of Hormone Replacement Therapy

The popularity of hormone replacement therapy peaked in the 1990s. It was around that time that reports started to emerge suggesting that hormone replacement therapy increased the risk of heart disease and breast cancer. Those risks were confirmed in a major study called the Woman’s Health Initiative that was published in 2002.

That study caused a major shift in how the medical community regarded hormone replacement therapy. Within a few years doctors shifted from recommending hormone replacement therapy for every woman with menopausal symptoms to recommending it only in cases where the symptoms were debilitating and only for the shortest possible time.

The effect on women’s health was huge. In fact, switching from universal hormone replacement therapy to targeted hormone replacement therapy remains the single most effective public health measure for reducing the incidence of breast cancer. It is more effective than any of new drugs and measures to improve breast cancer screening since then.

I wish I could tell you that was the end of the story. But recent studies have suggested that hormone replacement therapy also increases the risk of dementia. Unfortunately, most of those studies have had flaws, so the link between hormone replacement therapy and dementia has remained controversial – until now.

The study (N Pourhadi et al, British Medical Journal, 382, e072770, 2023) I will describe today was designed to provide a more definitive test of this hypothesis.

How Was This Study Done?

This was done in Denmark and used the Danish health registries. As Americans, you might not be aware of what a rich resource those health registries are. One advantage of socialized medicine is that every aspect of your health is tracked and recorded from cradle to grave.

[I’m not sure I would be comfortable with our government knowing that much about me, but it is a treasure-trove of information if you want to conduct a study like this one.]

The authors used the Danish National Health registries to:

Identify all Danish women aged 50-60 who had no incidence of dementia and were not on hormone replacement therapy as of January 1, 2000.

Identify 5589 women (1.8% of the population) from this group who were diagnosed with dementia between January 1, 2000 and December 31, 2018 and match them with 55,890 controls who remained dementia-free through the end of 2018.

Using the National Prescription registry, they were able to track which women used hormone-replacement therapy, what kind of therapy it was (there are several variations of hormone replacement therapy), and how long they remained on hormone replacement therapy.

The average age at which hormone replacement therapy began was 53, and the average duration of use was 3.8 years. The average age of a dementia diagnosis was 70.

Does Hormone Replacement Therapy Cause Dementia?

When the authors compared women who used an estrogen-progestin combination hormone replacement therapy (the most common kind) with women who never used hormone replacement therapy, the hormone replacement therapy users were:

24% more likely to develop dementia of any kind.

21% more likely to develop late-onset dementia.

22% more likely to develop Alzheimer’s disease.

Longer duration of hormone replacement use was associated with an increased risk of dementia. The increased risk of dementia was:

21% for ≤ 1 year duration.

39% for 8-12 years duration.

74% for > 12 years duration.

The age at which hormone replacement therapy was begun had a slight effect on dementia risk. The increased risk of dementia was:

26% when it was started at age 45-50.

21% when it was started at age 51-60.

Finally, other forms of hormone replacement therapy such as progestin only therapy and vaginal estrogen treatment did not have a statistically significant effect on dementia risk. But it was not clear whether this was due to a smaller sample size or whether it was a true null effect.

The authors concluded, “Menopausal hormone replacement therapy was positively associated with the development of all cause dementia and Alzheimer’s disease, even in women who received treatment at the age of 55 years or younger.”

The Pros And Cons Of This Study

The pros are obvious. This was a large, well-designed study. And its use of the Danish National Health registry and National Prescription registry allowed it to address the dementia risk of hormone replacement therapy in a comprehensive manner.

The cons are also obvious. This was an observational study. It can only show associations, not prove cause and effect. [I should note that it would be impossible to do a double-blind study to prove cause and effect. The size of the population group and the length of time required would make that kind of study unworkable.]

As I have said in previous issues of “Health Tips From the Professor”, the Achilles heel of observational studies is the possibility that a confounding variable (something else about the women who developed dementia) was the true cause of the observed outcome (in this case, increased dementia risk).

The authors did an excellent job of identifying known confounding variables that might have contributed to dementia and statistically correcting for them. However, the authors identified one potential confounding variable I would not have thought of.

In the words of the authors, “Further studies are warranted to determine whether these findings represent an actual effect of menopausal hormone therapy on dementia risk, or whether they reflect an underlying predisposition in women in need of these treatments.”

In case you need a translation, the authors are saying that it is possible that certain women have an underlying disease state or genetic predisposition that makes them very sensitive to menopausal symptoms (which increases the likelihood that they would receive hormone replacement therapy to reduce their symptoms) and increases their risk of dementia. In that case, it would be the underlying medical condition or genetic predisposition that was responsible for the increased dementia risk, not the hormone replacement therapy.”

I consider that unlikely, but it does warrant future studies.

Is Hormone Replacement Therapy Right For You?

Ultimately, this is your decision. But this is a decision you should make with your health care provider.

It is clear that hormone replacement therapy increases your risk of heart disease, breast cancer, and may increase your risk of dementia.

In part, your decision depends on the severity of your symptoms and your willingness to accept the risks associated with alleviating those symptoms.

But your health care provider can also help you consider family history and unrelated health conditions that may also increase your risk of these diseases. If your underlying disease risk is low, would you be more willing or less willing to accept the risks associated with hormone replacement therapy? Again, this is your decision.

And, if you decide to proceed with hormone replacement therapy, your health care provider can recommend the type of therapy and length of therapy that will minimize your risks.

The Bottom Line

Several recent studies have suggested that hormone replacement therapy may increase the risk of dementia, but this has remained controversial.

In this issue of “Health Tips From the Professor” I share a very large, well designed study that supports the link between hormone replacement therapy and dementia.

When the authors of this study compared women who had used hormone replacement therapy with women who never used hormone replacement therapy, the hormone replacement therapy users were:

24% more likely to develop dementia of any kind.

21% more likely to develop late-onset dementia.

22% more likely to develop Alzheimer’s disease.

For more information on the strengths and weaknesses of this study and a discussion of whether hormone replacement therapy might be right 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

Can Lifestyle Overcome Bad Genes?

January 31, 2023 by Dr. Steve Chaney

Lifestyle, Genetics, And Dementia Risk

Author: Dr. Stephen Chaney

Alzheimer’s disease and other forms of dementia are among the most feared diseases of aging. What use is it to have a healthy body, a loving family, and a successful career if you can’t remember any of it? You should be able to enjoy your Golden years, not see them slip through your fingers.

If you have a family history of dementia or have sent your DNA off for testing and learned you are genetically predisposed to dementia, you are probably worried.

Perhaps the scariest thing about Alzheimer’s is that the medical community has no answers. There are no drugs to prevent or cure Alzheimer’s and brain transplants are out of the question. Some medical professionals will tell you nothing can be done, but is that true?

Before I answer that question let me share a fictional story because it provides a clue. In 1997, when I was still a relatively young scientist, I saw a film called GAATACA. [If you are looking for an entertaining film to watch, it is still available on some streaming services.]

This film envisioned a future society in which parents had their sperm and eggs sequenced so that their children would be genetically perfect. In that society the term “love child” had been redefined as a child who had been conceived without prior DNA sequencing.

The hero of this film was, of course, a love child. He was born with a genetic predisposition for heart disease. He was considered inferior, a second-class citizen of this future world.

Without giving away the plot of the film (I don’t want to spoil the enjoyment for you if you are thinking of watching it), he overcame his genetic inferiority. With a strict regimen of diet and physical fitness he became stronger and healthier than many of his genetically perfect peers.

This is when I first began to realize that our genes do not have to determine our destiny. We have the power to overcome bad genetics. We also have the power to undermine good genetics.

With that in mind, let’s return to Alzheimer’s. Studies have suggested that a healthy lifestyle can help reduce your risk of developing Alzheimer’s and other forms of dementia. But what about genetics? Will a healthy lifestyle only reduce your risk of dementia if your genetic risk is low, or will it be equally effective when your genetic risk is high? Can lifestyle overcome genetics?

The current study (A Tin et al, Neurology, 99: e154-e163, 2022) was designed to answer these questions.

How Was This Study Done?

This study included 11,561 participants from the Atherosclerosis Risk In Communities (ARIC) study. The ARIC study recruited middle-aged adults (average age of 54) from both urban and rural areas of the United States and followed them for 26 years. The participants were 57% female and 53% white.

Simply put, the study was designed to look at the effect of a healthy lifestyle on the genetic risk of developing dementia.

A healthy lifestyle was defined based on something called “Life’s Simple 7” (LS7) score.

The LS7 score was developed by the American Heart Association to define the effect of lifestyle on the risk of developing heart disease. However, it works equally well for defining the effect of lifestyle on risk of developing dementia.

The LS7 score consists of 7 modifiable health factors.

- The factors are diet, physical activity, BMI (a measure of obesity), smoking, total cholesterol, blood pressure, and fasting blood glucose.

The data for deriving the LS7 scores were derived from data gathered from each participant when they enrolled in the ARIC study.

- Diet was assessed by a 66-item food frequency questionnaire.

- Physical activity and smoking were assessed in separate questionnaires.

- BMI, blood pressure, total cholesterol, and fasting blood glucose were measured during a visit to a designated clinic at the beginning of the study.

Each modifiable health factor was separated into 3 categories (ideal, intermediate, and poor) and the highest score was assigned to the ideal category. The LS7 score was the sum of the scores from all 7 modifiable health factors.

Genetic risk of developing dementia was defined based on something called “The Genetic Risk Score” (GRS).

We have known for years that individuals of European descent who have the APOE ɛ4 gene variant have a 2 to 5-fold increased lifetime risk of developing dementia.

In recent years scientists have discovered several additional gene variants that increase the risk of dementia.

These have been combined with APOE ɛ4 to create a Genetic Risk Score for dementia.

The Genetic Risk Score for each participant was determined by DNA sequencing at the beginning of the study, with the highest score indicating the greatest risk for developing dementia.

The onset and severity of dementia were determined based on 7 clinic visits during the study.

Questionnaires were administered at each visit to assess self-reported dementia symptoms.

Cognitive tests were administered at visits 2 and 4.

Detailed cognitive and functional assessments were conducted at visits 5, 6, and 7.

The data were reviewed by an expert committee of physicians and neuropsychologists to determine dementia status.

Lifestyle, Genetics, And Dementia Risk

At the end of the 26-year study:

When participants with the highest Genetic Risk Scores were compared to those with the lowest Genetic Risk Scores:

- European American participants were 2.7-fold more likely to develop dementia.

- African American participants were 1.55-fold more likely to develop dementia.

When participants with the highest LS7 (healthy lifestyle) scores were compared to those with the lowest LS7 scores:

- European American participants were 40% less likely to develop dementia.

- African American participants were 17% less likely to develop dementia.

- A healthy lifestyle decreased the risk of developing dementia to a comparable extent at all levels of genetic risk for dementia.

The authors concluded, “Higher LS7 scores [a measure of a healthy lifestyle] are largely associated with a lower risk of incident dementia across strata of genetic risk [at all levels of genetic risk], supporting the use of LS7 [a healthy lifestyle] for maintaining brain health and offsetting genetic risk. More studies with larger study populations are needed…”

I should briefly comment on why African Americans were less responsive to both genetic risk and a healthy lifestyle than European Americans. The reasons for these discrepancies are not known, but:

There are socioeconomic factors and health disparities that increase the risk of dementia that are not included in the LS7 score.
A recent study has identified genetic risk factors for dementia that are unique to African Americans that are not included in the genetic risk score used in this study.

Can Lifestyle Overcome Bad Genes?

Dr. James Watson, who was co-discoverer of the DNA double helix and was heavily involved in the sequencing of the human genome, asked that he not be told about his risk of developing Alzheimer’s when his own DNA was sequenced in the early 2000’s. His reasoning was, “Why know the risk if you can’t change it?”

If the study I discussed today is true, you can modify the risk. Your genes don’t have to be your destiny. But is it true?

There is good reason to believe it might be true. Multiple studies have shown that each of the health factors included in LS7 score reduce the risk of developing dementia. However, most of those studies have not looked at the interaction between a healthy lifestyle and genetic risk.

Fortunately, there is another recent study that looked at the interaction between a healthy lifestyle and genetic risk of developing dementia.

This study used a different database (The UK Biobank study which enrolled 500,000 participants) and different criteria for defining a healthy lifestyle (diet, physical activity, smoking, and alcohol use).

However, the conclusions of this study were very similar:

People at high genetic risk were almost twice as likely to develop dementia as those at low genetic risk.

A healthy lifestyle decreased the risk of developing dementia by about 40% for both people at high genetic risk and for people at low genetic risk.

But this study went one step further than the study I discussed in this article. The British study reported that:

People at low genetic risk and an unhealthy lifestyle (the typical American) were just as likely to develop dementia as people at high genetic risk and a healthy lifestyle.

In other words, bad genetics does not doom you to Alzheimer’s and dementia. A healthy lifestyle can cut your risk almost in half. Conversely, good genetics is not a “Get Out of Jail Free” card. You can squander the advantage of good genetics with an unhealthy lifestyle.

And, just like the hero of the movie I discuss at the beginning of this article, a healthy lifestyle may be able to overcome bad genes and make you just as healthy (with respect to the risk of developing dementia) as people with good genes and an unhealthy lifestyle – which includes most Americans.

The Bottom Line

If you have a family history of dementia or have sent your DNA off for testing and learned you are genetically predisposed to dementia, you are probably worried.

Studies have suggested that a healthy lifestyle can help reduce your risk of developing Alzheimer’s and other forms of dementia. But what about genetics? Will a healthy lifestyle only reduce your risk of dementia if your genetic risk is low, or will it be equally effective when your genetic risk is high? Can lifestyle overcome genetics?

A recent study was designed to answer these questions. It found:

When participants with the highest Genetic Risk Scores were compared to those with the lowest Genetic Risk Scores:

- They were 1.5 to 2.7-fold more likely to develop dementia.

When participants with the highest LS7 (healthy lifestyle) scores were compared to those with the lowest LS7 scores:

- They were 17% to 40% less likely to develop dementia.

A healthy lifestyle decreased the risk of developing dementia to a comparable extent at all levels of genetic risk for dementia.

This, and other studies discussed in this issue of “Health Tips For The Professor” suggest that your genes don’t have to determine your destiny. You can overcome bad genes with a healthy lifestyle.

For more details on this study, read the article above.

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

Can Diet Protect Your Mind?

September 13, 2022 by Dr. Steve Chaney

Which Diet Is Best?

Author: Dr. Stephen Chaney

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

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

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

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

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

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

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

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

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

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

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

How Was The Study Done?

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

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

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

The Mediterranean diet.

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

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

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

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

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

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

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

Finding ways around familiar streets (measuring visuospatial skills).

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

Can Diet Protect Your Mind?

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

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

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

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

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

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

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

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

There were a few other significant observations from this study.

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

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

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

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

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

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

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

Which Diet Is Best?

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

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

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

Was specifically designed to reduce cognitive decline.

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

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

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

Which Foods Are Best?

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

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

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

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

What Does This Study Mean For You?

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

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

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

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

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

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

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

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

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

Eat more plant foods and less animal foods.

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

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

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

The Bottom Line

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

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

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

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

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

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

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

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

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.

Belly Fat Increases Your Risk Of Dementia

December 17, 2013 by Dr. Steve Chaney

Does Belly Fat Make You Dumb?

Author: Dr. Stephen Chaney

In last week’s “Healh Tips From the Professor” I told you that abdominal obesity (otherwise known as “belly fat“) increases your risk of dying from both heart disease and cancer.

But you probably knew that already.

This week I’m going to tell you about a recent study that breaks new ground and should really grab your attention.

Belly Fat Increases Your Risk Of Dementia

This week’s study shows that abdominal obesity dramatically increases your risk of developing dementia as you age (RA Whitmer et al, Neurology, 71: 1057-1064, 2008).

This study involved 6,583 members of Kaiser Permanente of Northern California, ages 40 to 45, who had their abdominal obesity measured between 1964 and 1973. The investigators then pulled their medical records between 1994 and 2006 when they were between 73 and 87 years old and asked how many of them had dementia.

The results may shock you.

The participants were divided into five groups based on their abdominal circumference. Those with the largest abdominal circumference were nearly 3 times more likely to have developed dementia than those with the smallest abdominal circumference. And that was after the data were adjusted for age, sex, race, education, diabetes, hypertension, hyperlipidemia, stroke and heart disease – all factors that are known to affect the risk of dementia.

Belly Fat Is Worse Than Overall Obesity

Interestingly enough the abdominal circumference was a better predictor of dementia risk than was BMI, the most frequently used measure of obesity.

Those subjects who had high abdominal obesity and normal BMI had a 2-fold increased risk of developing dementia

Those subjects who were obese but had normal abdominal circumference had only an 80% increased risk of developing dementia.

Of course, those people who were both obese and had a large belly were the worst off – they had almost a 4-fold increased risk of developing dementia.

So where you store your fat is more important than the total amount of fat, but you probably knew that already.

You Can Reduce Your Risk Of Dementia

Now let’s get to the question that I’m sure that many of you are dying to ask me: “If I don’t like what I see when I look into the mirror, am I doomed to develop dementia when I get older?”

The answer is no. Most experts feel that the effects of abdominal obesity are reversible.

But the time to act is now!

If you wait until you get older, you might just forget that you ever read this article.

The Bottom Line

The bad news is that belly fat increases your risk of developing dementia as you get older by as much as 3-fold.

The good news is that dementia is not inevitable. You can reverse the increased risk of dementia by losing the belly fat

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

Omega-3 Fatty Acids And Brain Health

December 3, 2013 by Dr. Steve Chaney

Is it How Much You Eat, or How Much You Keep?

Author: Dr. Stephen Chaney

Why do some studies conclude that omega-3 fatty acids are essential for a strong mind, a strong heart and will wipe out inflammation – while other studies suggest that they are ineffective? The simple answer is that nobody really knows.

However, in the process of reviewing two recent studies on omega-3 fatty acids and brain health I made an interesting observation that offers a possible explanation for the discrepancies between studies. And if my hypothesis is correct, it suggests that the design of many of the previous studies with omega-3 fatty acids is faulty.

Omega-3 Fatty Acids And Brain Health

The first study (J.K. Virtanen et al, J Am Heart Assoc, 2013, 2:e000305 doi: 10.1161/JAHA.113.000305) looked at the effect of omega-3 fatty acids on brain function in older adults (>65 years old). It concluded that high omega-3 levels were associated with better white matter grade and a 40% reduction in subclinical infarcts (Sorry for the technical jargon – but both of those are good things in terms of brain function for those of us who are getting a bit older).

The second study (C. M. Milte et al, J of Attention Disorders, 2013, doi: 10.1177/1087054713510562) looked at the effect of omega-3 fatty acids on children (ages 6-13) with ADHD. It concluded that high omega-3 levels were associated with improved spelling and attention and reduced oppositional behavior, hyperactivity, cognitive problems and inattention.

What Is The Common Thread In These Studies?

Why, you might ask, am I comparing a study in the elderly, where the concern is retention of cognitive skills, with a study on ADHD in children?

That’s because there is a very important common thread in those two studies. It wasn’t the amount of omega-3 fatty acids in their diet that counted. It was the levels of omega-3 fatty acids in their blood that made the difference.

The first study included a detailed dietary history to estimate the habitual intake of omega-3 fatty acids in the participants.

There was no correlation between estimated dietary intake of omega-3 fatty acids and any measure of brain function in those older adults.

However, there was a strong correlation between blood levels of omega-3s and brain health in that population group.

The second study was actually a placebo controlled intervention study in which the children were given 1 gm/day of either omega-3 fatty acids or omega-6 fatty acids.

Once again, there was no correlation between dietary intake of omega-3 or omega-6 fatty acids and any outcome related to ADHD.

However, there was a strong correlation between blood levels of omega-3 fatty acids or omega-3/omega-6 ratio and improvement in multiple measures of ADHD.

How Could The Effect of Dietary Intake And Blood Levels Of Omega-3s Be So Different?

Both studies were relatively small and suffered from some technical limitations, but the most likely explanations are:

Inaccurate recall of the participants as to what they eat on a habitual basis. (study 1)

Individual differences in the ability of participants to convert short chain omega-3 fatty acids (found in foods such as canola oil, flaxseed oil and walnuts) to the beneficial long chain fatty acids (found in cold water fish). (study 1)

Poor compliance in taking the supplements. (study 2)

Why Are These Studies Important?

The most important insight to come out of both of these studies is that it is essential to actually measure blood levels of omega-3 fatty acids and not just rely on dietary intake or supplementation for a valid clinical trial.

That’s a concern because blood measurements of omega-3 fatty acids are expensive and have not been a part of many of the clinical studies that have been performed to date. Even the largest, best designed clinical study is worthless if the dietary recalls aren’t accurate or people don’t take their capsules.

We need to go back and reevaluate many of the clinical studies that have been published.

We need to ask:

Are their conclusions valid?

Did some studies fail to show that omega-3s were effective simply because they only measured dietary intake and not how much of the omega-3s actually accumulated in the blood?

The Bottom Line

High blood levels of omega-3s in the blood correlated with improved brain health in the elderly and reduced ADHD symptoms in children

These studies were small, but they are consistent with a number of other studies that have come to similar conclusions.

Blood levels of omega-3s are better predictors than dietary intake for evaluating the health benefits of omega-3 fatty acids.

Many previous studies that failed to find an effect of omega-3 fatty acids on brain health, heart health or inflammation did not actually measure blood levels of the omega-3 fatty acids. These studies should be reevaluated.

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.