OmegaMatters: Episode 16

Hosts: Drs. Bill Harris & Kristina Harris Jackson

Guest: Dr. Aleix Sala-Vila

Background and Key Takeaways:

Dr. Sala-Vila received his PhD in biomedicine from the University of Barcelona in 2004, and his research has involved the role of bioactive compounds in reducing the incidence of chronic disease, with a particular focus on Omega-3s. He’s completed four post-doctoral fellowships, including one with Dr. Phil Calder, has published 45 papers on fatty acids, and he’s one of the primary scientists at the Fatty Acid Research Institute.

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Dr. Kristina Harris Jackson: Welcome to OmegaMatters. I’m Kristina, this is Bill, and today we’re talking with Dr. Aleix Sala-Vila about a newly-published paper on DHA and Alzheimer’s. Dr. Sala-Vila received his PhD in biomedicine from the University of Barcelona in 2004, and his research has involved the role of bioactive compounds in reducing the incidence of chronic disease, with a particular focus on Omega-3s. He’s completed four post-doc- doctoral fellowships, including with Dr. Phil Calder, has published 45 papers on fatty acids, and he’s one of the primary scientists at the Fatty Acid Research Ins- Institute. So thanks for talking with us today, Aleix.

Dr. Aleix Sala-Vila: My pleasure. Thanks for your invitation.

Dr. Kristina Harris Jackson: So the paper we’re talking about today has just recently been published and in it you’re reporting that higher red blood cell levels of DHA are associated with lower risk of developing Alzheimer’s disease and dementia. So why did you have this question, and what prior information suggested that you should look into this area?

Dr. Aleix Sala-Vila: Well, that’s a good question. as many of you know there is no available track today just to treat or delay or reverse Alzheimer’s incidence, so while we are waiting for effective tracks it’s of a great importance to put our thoughts toward preventive strategies.

Dr. Aleix Sala-Vila: On the other side, we know that the brain is highly enriched in omega-3 DHA, which it starts to accumulate even before we are born, so during the last trimester of gestation there is a demand by the fetus for this fatty acid. Meaning that it may have a critical role in the brain function. So finally there’s an increasing belief that what is good for our heart will be good for our brain, and as you know Omega-3 fatty acids have been some of the most studied components of the diet in relation to health of our heart.

Dr. Aleix Sala-Vila: So by combining these three ideas of fatty acids which is critical to the brain, need to go for preventive strategies to prevent, or at least to delay, the onset, the appearance of the clinical symptomatology of Alzheimer’s. And then, what is good for our brain is good for heart. So there’s a huge effort nowadays in research on Omega-3s and brain, and while we are lucky to have this amazing information, of this nice cohort, of the Framingham Offspring, well it was a good opportunity to be part of this of this exciting combination of different players.

Dr. Bill Harris: Yeah. So you mentioned the Framingham Offspring Cohort, can you tell our listeners what that is?

Dr. Aleix Sala-Vila: Yes, so Framingham has been extremely important in terms of methodological research. It’s a huge cohort that has been studied for a long, long time. So we focused on the Framingham Offspring cohort, meaning that these are the sons of the original participants of the Framingham Heart Study.

Dr. Aleix Sala-Vila: We studied around 1,500 participants, beyond 65 years old. That’s the definition of old people, no? So we decided to establish this cutoff. And we had all kinds of information related to the risk of Alzheimer’s. We had, of course, data on the fatty acid composition of red blood cells, but these participants, we knew that they were free of dementia baseline, so their red blood cells were collected. And we had been following them for a long, long time in a regular manner.

Dr. Aleix Sala-Vila: And, more importantly, we knew about their genetic risk of Alzheimer’s disease because Alzheimer’s disease in carriers of one specific allele of one protein, which is key for lipid transport in our body. So all of us, we have a genotype of this lipoprotein, so we knew all the information of this specific high-risk protein for all the participants.

Dr. Bill Harris: Okay, great.

Dr. Kristina Harris Jackson: Excellent. So can you just summarize for a non-scientist what you actually found in this study?

Dr. Aleix Sala-Vila: We found that compared to those with the lowest amount of DHA in red blood cells, the ones with the highest amount of red blood cell DHA, meaning higher consumption of this fatty acid, it was associated with a decreased risk by half of having Alzheimer’s disease. In relation, we did some calculations, and we found that in case that you are going to have Alzheimer’s, you were going to have five extra years of life free of Alzheimer’s disease.

Dr. Bill Harris: If you have the highest level of DHA?

Dr. Aleix Sala-Vila: Yeah, compared to the lowest level of DHA. So, having highest levels, it was good for you. And you can increase this level of DHA in your blood by, for instance, consuming fatty fish or consuming fish oil.

Dr. Kristina Harris Jackson: Mm-hmm.

Dr. Aleix Sala-Vila: Or maybe you are lucky person with unusually high levels. But, well, if you want to increase your levels, the easiest and quickest way is just to consume fatty fish or consume fish oil.

Dr. Kristina Harris Jackson: Mm-hmm.

Dr. Bill Harris: So what does this study mean that if you’re 65 years old and you start taking fish oil, that you’ll put Alzheimer’s disease off for five more years?

Dr. Aleix Sala-Vila: Well, it’s difficult to say because this was an observational study. This means that there is no casualties. We observed that people with higher levels of DHA, lower risk of Alzheimer’s, but maybe these persons, okay, if you eat a lot of DHA, maybe you take a lot of care of your health, you are fully aware of the importance of your lifestyle in reducing the risk of Alzheimer’s, so this could only be this connection, huh? With no doubt at all. It could only be obtained by a randomized controlled trial. This study was just observational, so we tried to focus on different aspects of lifestyle, and we got an association, but not a direct cause.

Dr. Aleix Sala-Vila: However, I think that I said before, if we want to achieve a healthy aging, I think it’s never too late, but never too early, to start to implement, you know, better lifestyle habits. So it’s important to eat well, to manage your stress, and have social interactions. It’s important also to sleep well, and maybe in the future we will have a direct study proving that if you eat fish oil, you can reduce significantly the risk of Alzheimer’s disease.

Dr. Aleix Sala-Vila: So we are currently working on that, trying to define these type of studies, trying to identify which persons would get the highest benefits of this interaction. And maybe, maybe it’s important not to target everyone, maybe it’s important to identify people with low levels of DHA and then treat them with fish oils just to help them to correct these low levels Omega-3.

Dr. Bill Harris: Yeah.

Dr. Kristina Harris Jackson: Mm-hmm.

Dr. Bill Harris: So you mentioned that one of the typical criticisms of an observational study like this is that people who have a high DHA may just be healthy and have many other healthy factors. Do you know of any other study that has not looked at the Omega-3 question, but has looked at that question multiple healthy lifestyle factors and its relationship with Alzheimer’s disease?

Dr. Aleix Sala-Vila: Yes, actually. There is, for instance, a very important one, which is called FINGER. It’s a multimodal study involving not only diet but also diet cognitive tools to improve cognitive function, so just training your memory.

Dr. Bill Harris: All those things help.

Dr. Aleix Sala-Vila: Yep, all things help. It’s risky just to rely on just one thing. But, well, if you can choose one good thing.

Dr. Kristina Harris Jackson: So have there been any studies actually done giving Omega-3s or Omega-3 drugs and incidence of Alzheimer’s disease, dementia, or biomarkers of that? Have there been those causative studies done yet?

Dr. Aleix Sala-Vila: Yeah. Well, if we are talking these randomized controlled trials, just to say fish oil can delay Alzheimer’s disease.

Dr. Kristina Harris Jackson: Mm-hmm.

Dr. Aleix Sala-Vila: So there are no effects. But we are still at the beginning of understanding what’s going on with this type of disease. We are just starting to understand the mechanisms of the disease. So if you go to Congress and present a study looking at the effect of diet on Alzheimer’s and diet, there is no money of research. Most of the research in the field relates to biomarkers, new ways to identify the disease before the onset of the clinical symptoms, trying to find hallmarks and this kind of stuff. But for sure, maybe in 20 or 30 years the link between diet and Alzheimer’s will be no doubt at all. For instance, I think it will be pretty similar with what happened happening 30 or 40 years ago with cardiovascular disease and diet. Nowadays, nobody doubts it.

Dr. Aleix Sala-Vila: So if you go to a doctor, the first thing that is, “Do you smoke? Okay, quit smoking.” And then, take all of the salt out of your diet. So you need to improve your blood pressure. So maybe this will happen in 30 years. So we are first understanding the disease, and we are also considering that this is a long-term disease, so it’s difficult to design the trials. You need a lot of power, a lot of money, just to follow a lot of people for a long, long time.

Dr. Aleix Sala-Vila: So far in terms of incidence of Alzheimer’s disease, there are no trials yet. We have been having trials on changes in cognitive performance, which is the hallmark of Alzheimer’s disease, so suddenly the cognitive performance goes down, which is called mild cognitive impairment. And yes, we have been seeing different trials, maybe three years, two years of follow-up, which is not a long time. But, well, it’s really complicated. And these trials yielded, you know, mixed results. Some of them seem like it’s good, so fish oil can delay this fall in cognitive decline, and some of them were not so good.

Dr. Aleix Sala-Vila: It’s important to identify first which type of population, at what time we should go. So if there is some decline, it’s too late DHA or DHA plus EPA, another fish oil. DHA plus EPA, okay, which is the dose, the nice dose? Does the chemical form matter? Should it go along with, as we were saying, with changes in the lifestyle? So nowadays, we are trying to define, you know, just to improve the design of the, of these studies.

Dr. Aleix Sala-Vila: Because it’s really difficult to conduct a randomized controlled trial, so I think that the best thing is okay, let’s stop, let’s think, let’s identify, you know, which population, which is the right dose. There are a lot of people working on that.

Dr. Bill Harris: Any downside to starting to take more DHA in in your 30s or 40s?

Dr. Aleix Sala-Vila: No, not at all. What you do in your 40s will echo in your 60s (laughing), so maybe it’s never too late. And if you can start in your 20s, it’s good, because maybe, okay, it won’t help to reduce your risk of Alzheimer’s because maybe you are never going to have Alzheimer’s disease, but it will help your cardiovascular health. So I think that there’s no downside at all. It’s never too late or early to start taking care of yourself.

Dr. Bill Harris: Great.

Dr. Kristina Harris Jackson: Yeah, and I guess the other question was that you found a connection to DHA, but the Omega-3 index and EPA alone did not predict Alzheimer’s. What do you think about that?

Dr. Aleix Sala-Vila: This is extremely puzzling. EPA and DHA share actions, they compete, one can be transformed into the other one. We must say that the important fatty acid you have is in your brain. But some observational studies similar to ours found that EPA was the fatty acid with higher association, so the strongest associations, while DHA, not so much. We still don’t know.

Dr. Bill Harris: No, that was depression.

Dr. Aleix Sala-Vila: We still don’t know.

Dr. Bill Harris: Right?

Dr. Aleix Sala-Vila: But, for instance, if you take fish oil, most of the fish oils contain both EPA and both DHA, so it’s difficult to distinguish. I don’t think that they have really different actions, so I think that they share the actions. They can act synergistically, they don’t compete, so, well, I think that, okay, maybe the association was strong for DHA, not so strong for EPA, meaning that the Omega-3 index yielded non-significant. But I must say, so the risk was reduced without reaching a statistical significance.

Dr. Bill Harris: Right.

Dr. Aleix Sala-Vila: So I think that we are maybe trying to put too much focus on whether EPA and DHA have different actions. I think that they act pretty much the same. So people that are taking fish oil, just make sure you have both in there. And there’s a lot of fish oil products, especially for heart disease, that are higher EPA, but usually they’re so high dose that you do get a decent amount of DHA as well. But like a pure EPA maybe- maybe you’d wanna steer towards like something that has both, I would think.

Dr. Bill Harris: Any idea how much DHA you should take to get a red cell DHA level over 6%?

Dr. Aleix Sala-Vila: Oh.

Dr. Bill Harris: That’s kind of where the highest group was.

Dr. Aleix Sala-Vila: Well, that’s another important question. The dose is quite important. Because, for instance, we saw that the associations were stronger in participants apolipoprotein E4 allele (APOE4), which is an important protein in the lipid transport. This type of population has heightened demands for DHA, because they have impaired metabolism of DHA, so the levels are lower.

Dr. Aleix Sala-Vila: So maybe they will have a higher demand, and in this way, I must say or I must refer to the works of Dr. Hussein Yassine from University of Southern California. He has been testing different doses, and he keeps saying that with less than 1 gram per day, there is not much effect in trying to treat that. So I’m referring to his work above 1 gram per day. I think that with this dose, you can significantly increase your Omega-3 index, as well as the amount of DHA in your red blood cells.

Dr. Bill Harris: Yeah.

Dr. Kristina Harris Jackson: And do you mean 1 gram of DHA alone, or EPA and DHA?

Dr. Aleix Sala-Vila: They were testing, I think that they were just testing DHA.

Dr. Kristina Harris Jackson: Well, we think this is a really interesting and hopeful paper, and we’re really glad that you’ve been able to spend the time to work on some of these really important questions. So do we have any more questions?

Dr. Aleix Sala-Vila: I just want to say that I was privileged to have this information, so a lot of participants with red blood cells measured, with a lot of information, with the information on genetic risk, which is something that is not so usual. So I was privileged to- to have this opportunity and, well, it was lucky because we found the association.

Dr. Bill Harris: Great.

Dr. Kristina Harris Jackson: It’s nice when it works out.

Dr. Bill Harris: You got it.

Dr. Kristina Harris Jackson: Well, thank you so much, Aleix. And we will probably talk to you again on this podcast, because you guys are cranking out papers like crazy.

Dr. Aleix Sala-Vila: Thank you so much for the invitation. Bye.

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