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Fish oils & Omega-3s: Sustainability, safety and testing with Emma Sutherland and Dr. Kristina Harris Jackson

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Fish oils & Omega-3s: Sustainability, safety & testing Emma Sutherland & Dr. Kristina Harris Jackson

Join Dr. Kristina Harris Jackson, omega-3 specialist, and FX Medicine Ambassador Emma Sutherland as they deep dive into fish oils. As clinicians we understand the value of omega 3s but having a full understanding of their origins, quality, specific functions, optimal dosing and safety during various life stages can be confusing. This podcast covers all of those aspects – backed up by some impressive research. Dr. Harris Jackson and Emma discuss the GOED’s stance of fish and fish oil accessibility, quality and safety for global health, the differences between ALA, EPA and DHA, the importance of red blood cell omega-3 levels and testing, and finally Dr. Harris Jackson’s specialty: omegas for preconception, pregnancy and post-natal health to help expand current understanding of the essential omega-3s. 

Covered in this episode

[01:00] Welcoming Dr. Kristina Harris Jackson
[02:12] The Global Organization for EPA & DHA Omega-3s (GOED) and why it is so important
[06:54] Differences between the types of omegas
[10:00] EPA and DHA mechanisms of action
[13:42] How can we avoid oxidation in omega oil products 
[19:19] Vegan alternatives to marine-based omegas: algal oils
[22:50] Choosing the right supplement for your patient
[26:58] Can we translate epidemiological research on omegas into clinical practice?
[30:39] Controlling the ratios of EPA and DHA
[32:55] Who most needs omega3s?
[35:47] Omegas for cognitive decline
[39:58] Can omegas reduce all cause mortality?
[44:24] Omegas in preconception 
[52:43] Requirements for omega-3s during pregnancy 
[59:11] Quantities of DHA in breastmilk 
[01:04:54] Fish consumption vs supplementation
[01:09:53] Thanking Dr. Kristina and final remarks

Key takeaways

  • The Global Organisation for EPA and DHA (GOED) advocate and test for the best quality fish-oil products. GOED have a monograph stipulating their quality limits. Look out for the GOED symbol when choosing fish oils. 
  • What’s what: EPA, DHA, ALA, omega-3 PUFA’s? 
    • ALA 18-C can be converted into EPA and DHA. Humans can enzymatically convert 5% ALA into EPA and 1% into DHA – a poor conversion rate. Plant based sources. 
    • EPA 20-C Very efficient uptake from dietary (marine) sources. Mainly for cellular processes (not an energy source). Anti-inflammatory and pro-resolving mediator metabolites. 
    • DHA 22-C Very efficient uptake exclusively from dietary marine sources. Mainly for cellular processes (not an energy source). Anti-inflammatory and pro-resolving mediator metabolites. 
  • Testing omega status at the 3–4-month period can assist clinicians quantify the efficacy of a fish oil supplement. 8% omega-3 index is optimal. 
  • Studies show vegan levels may be as low as 4% omega-3 index. Algal oil dosing should be 1:1 to marine derived EPA/DHA. 6% blood level DHA is recommended for vegans (for cost effectiveness). To reach a good level of 8% this requires 1g EPA/DHA p/day.  
  • Forms matter: triglyceride-based supplements are better absorbed vs ethyl-ester based (which might cause absorption issues, can be overcome by eating with food) forms. 
  • Omega’s positively impact blood flow through endothelial flexibility and reducing platelet aggregation that encourage clearance of inflammatory mediators and assists with delivering cells their nutrition. 
  • Ingesting 200-300mg DHA for pre-natal care is a well-researched dose for increasing blood DHA. During pregnancy further increases have been observed at the same dose – leading to longer gestational age. This effect on blood is not true for breastfeeding women however DHA rises in breastmilk.  

Resources discussed and further reading

Dr. Kristina Harris Jackson

Dr. Kristina Harris Jackson
Dr. Kristina's Publications
Fatty Acid Research Institute (FARI)

Fish Oil testing and safety

The Global Organization for EPA & DHA Omega-3s (GOED)
GOED Monograph Version 8.1 (2022)
International Fish Oil Standards (IFOS)
Research: 'Fish Oil Contaminated with Persistent Organic Pollutants Induces Colonic Aberrant Crypt Foci Formation and Reduces Antioxidant Enzyme Gene Expression in Rats' (J Nutr. 2017)

Vegetarian sources of omega-3s

Research: 'Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: a review of the literature.' (Crit Rev Food Sci Nutr. 2014)
Research: Transgenic Canola Oil Improved Blood Omega-3 Profiles: A Randomized, Placebo-Controlled Trial in Healthy Adults (Front. Nutr., 2022)

Fish oils, brain health and cognition

UK Biobank  
Research: 'Association of fish oil supplementation with risk of incident dementia: A prospective study of 215,083 older adults.' (Clin Nutr. 2022)
Research: 'Association of Red Blood Cell Omega-3 Fatty Acids With MRI Markers and Cognitive Function in Midlife: The Framingham Heart Study' (Neurology, 2022)

Fish oils and mental health

Research: 'International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder,' (Psychother Psychosom. 2019) 

Fish oils and cardiovascular and metabolic health 

Research: Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial (JAMA, 2020)
Research: Association of Oily and Non-oily Fish Consumption and Fish Oil Supplements With Incident Type 2 Diabetes: A Large Population-Based Prospective Study (Diabetes Care, 2021)
Research: The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors (PLOS Medicine, 2009)

Omega-3s in preconception, pregnancy and lactation

Research: Baseline red blood cell and breast milk DHA levels affect responses to standard dose of DHA in lactating women on a controlled feeding diet (Prostaglandins Leukot Essent Fatty Acids, 2021)
Research: Omega‐3 fatty acid addition during pregnancy (Cochrane Database of Systematic Reviews, 2018)
Research: Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial (EClinicalMedicine, 2021)
Research: Relationships between seafood consumption during pregnancy and childhood and neurocognitive development: Two systematic reviews (Prostaglandins Leukot Essent Fatty Acids, 2019)


Emma: Hi, and welcome to FX Medicine where we bring you the latest in evidence-based integrative, functional and complementary medicine. 

FX Medicine acknowledges the traditional custodians of country throughout Australia where we live and work and their connections to land, sea, and community. We pay our respects to their elders, past and present, and extend that respect to all aboriginal and Torres Strait Islander peoples today.

On the line with us today is Dr. Kristina Harris, director of research at OmegaQuant Analytics. Kristina has a PhD in nutritional science and is an assistant professor in the Department of Internal Medicine at the University of South Dakota School of Medicine. 

Her primary area of research is omega-3s and maternal health. Today, we will be looking at some recent research and discussing omega-3s from different angles, the quality, relevant conditions that respond to omega-3s, and of course the prescribing options.

Welcome to FX Medicine, Kristina, thank you so much for being with us today.

Kristina: Thank you so much for having me.

Emma: Oh, it's our pleasure. Now I'd like to start with setting the scene. So, globally omega-3 essential fatty acids are a $1.4 billion industry, and most fish oils come from anchovies in Peru with the end oil being around 30% EPA and DHA per gram. And then the industry refines that oil to be higher strength EPA and DHA and also to remove any contaminants such as heavy metals.

Interestingly, the main reason people start taking omegas is because their health practitioner advised them to and that means that we, as clinicians, really need to have our finger on the pulse and be recommending omegas in a way that really aligns with the available research. 

Now, first of all, Kristina, can you explain who the Global Organisation for EPA and DHA are and why they're so important for our industry? I mean, this organisation is voluntary. It's voluntary membership, but they do agree to certain standards. And do you think this has helped overall quality within the industry?

Kristina: Yeah, that's a great question. And GOED is...well, we are members of it and it's really a trade group for EPA and DHA specifically, and so there's lots of different people who participate mostly fish oil manufacturers, all the way from the people who are doing the catching of the anchovies or other kinds of fish, processing them into crude oil, all the way down to encapsulation and branding. And then there are some seafood companies, pharma companies, and then people just interested in increasing the availability of EPA and DHA for people to be able to consume.

So because their main goal is really just to get people to eat more omega-3s, either from fish or fish oil basically, they want to make sure that issues in the market are addressed. And one of the biggest issues is quality of supplements. So that's, I think, the main reason why they started to...they have something called a monograph where they have all of these stipulations of the supplements should have no more than this amount of an oxidative stress marker or an oxidation marker. Is the oil being carefully cared for throughout the whole process from catching the fish, getting the oil, putting in the capsules?

And so they test the end product. They test the branded product off the shelves. They'll do a random sampling across the world. I think they're doing it once a year now, but I know with COVID it got slowed down. Those results are really just for the people who are in GOED to give them a heads up on what the sampling is. It's not public-facing in that way. If they're part of GOED, then they do agree for this testing and really almost all of them pass every level of the test, which is very rigorous.

But IFOS is more of that third-party supplement testing label that you would see and GOED kind of supports the larger industry behind it, but I think it does help with the transparency because they're very focused on it and they're doing these real-time tests. It is third-party, so it's like being audited, but it's not necessarily for consumers.

Emma: Yes, I actually read through that monograph, and it was incredibly technical. I was quite blown away by how technical it was.

Kristina: Yeah, they test a lot, so it's far more intensive than just there's an amount of EPA and DHA in a pill that they say that there is. It goes way beyond that.

Emma: Yeah, as a clinician, it was incredibly reassuring to know that all this work goes on behind the scenes, which I think most clinicians are just not aware of that any of that's going on.

Kristina: Yeah, it seems like for the most part, most of the reputable brands are doing what it takes and have a good process for their supplements. But the problem is there's so many brands. Anyone can start making supplements if they want to. And so it's just like, if you don't really know and you just go out on the internet and pick something, you may or may not be finding the reputable brand that's really doing the work. And I think just those small proportion of brands who aren't doing everything they can to get a good product can give everyone a bad name.

Emma: Yeah, yeah. I mean, what are the differences between the three types of omega-3s? There's EPA, DHA, and alpha-linolenic acid.

Kristina: Yeah, this is a great question and this causes huge confusion in the marketplace. More I think on the food side maybe than the supplement side, but it's both. 
So, they're all omega-3s, they're all polyunsaturated fatty acids first. And so they all have this structure where they're these fatty acids, so that's just very long chains of carbon, which means lots of carbons connected to each other. It's a really efficient way to store carbon, so it could then give us energy.

And then, ALA is kind of the parent omega-3. From ALA, we can make all different kinds of omega-3s, including EPA and DHA. But we can't make ALA. We can't put the double bond on the third carbon from the omega end. And so the body has enzymes to put double bonds on certain locations in the fatty acids. It doesn't have the one to make that omega-3 one, and so that's why it's essential. That's why ALA is usually focused on because it's kind of the original essential fatty acid along with linoleic acid, which is an omega-6 fatty acid. And so those two are the shortest chain of the polyunsaturated fatty acids, and they're the essential ones.

But the efficiency of how well we make EPA and DHA from ALA is pretty low. It does change from male to female and a lot of other things, but generally we'd say about 5% of ALA can be converted to EPA and about less than 1% makes it all the way to DHA.

Emma: Wow.

Kristina: There really seems to be a block at the conversion to DHA. So, EPA and DHA, they have more carbons, more double bonds, and they're much more rare in our diet. ALA is found in walnuts and flaxseed and canola oil, plant-based. You can get ALA from plants. EPA and DHA are, in nature, only found in seafood and fish, which is super interesting. So, they're called the marine fatty acids, and that's where they originate from. We can't naturally get them from plants.

Emma: Okay. So, we can really only convert across to EPA and DHA, but that conversion is really inhibited and is quite poor.

Kristina: It is quite poor from the research that we have done. But that pathway, we're still learning about it, even though we've been, you know? Things can change, and figuring out different ways to affect the conversion is something that people are really interested in. But from what we can tell, eating fish, you get so much more of a omega-3 dose than eating a lot of flaxseed. As far as the EPA and DHA levels, it's just there's no comparison, and it's quite amazing how efficiently the body takes up EPA and DHA and does not use it for energy. It puts it in membranes of your cells, and then it's used for other things, but it's not typically burned as energy.

Emma: Yeah, really interesting. And what are the main mechanism of actions for EPA and DHA? How are they working in our bodies?

Kristina: Yes, so this has been just a fascinating area of research for decades. I mean, people are still fascinated by these fatty acids because of all these mechanisms and clinical outcomes we're seeing. So, again, grain of salt. These mechanisms are our best guess at the moment of how we think omega-3, EPA, and DHA are having clinical effects for people.

The biggest one is probably around inflammation, and that's probably because inflammation is so core to so many of our disease processes. So, if you're going to affect that one thing, it can affect basically your entire body. So, EPA and DHA are metabolised by enzymes, and those metabolites will do a variety of things that are involved in the inflammation process. So, typically the omega-6s have a more pro-inflammatory metabolite, and the omega-3s have a less inflammatory, or a more anti-inflammatory, or a pro-resolving metabolite.

So, if you think about an inflammatory event, if it's, let's say a cut on your arm, your inflammation goes there. It wants to kill all the bacteria. It wants to close up the bleeding. It's very important. But after that's done, you need a mechanism for it to heal. And so the omega-3s are a part of that healing mechanism where those metabolites will be coming up hours after or days after the event, and they'll be cleaning out the debris, cleaning out the bacteria, making sure that all the excess inflammatory cells are taken care of so that information doesn't continue. You want it to happen and then stop.

So, the omega-3s, we think are doing that stopping piece. And also because of the ways omega-3s and omega-6s, they have a relationship in the membranes and the cell membranes for when omega-3s go up, they kind of decrease the omega-6s. And so there's also this aspect of, if you have higher omega-3, you're also lowering the inflammatory potential by lowering the amount of omega-6s. And so that's really a huge area.

And then also omega-3s have been shown over and over again to lower plasma triglyceride levels. So, they interact with the lipid and lipoprotein metabolism in that way very consistently, and they've been shown to slightly lower blood pressure. To me, I think of it as blood flow where they also intervene with platelet action, and so it seems like, in a lot of ways, they do allow for better blood flow throughout the body, which again affects so many systems.

So, they inhibit platelet function, which would allow you to... This is one of the worries people have is that, if you have too many omega-3s on board, you'll bleed too much. And it can be true if you do have a lot on board that you bruise more, that you're bleeding, your cut might bleed a little longer, but we've shown in a lot of papers that for severe bleeding events that are actually life-threatening, the omega-3s do not increase risk of that in any way even in surgery, any of that. In fact, sometimes makes it have better outcomes. But it's just that blood flow, lower inflammation, and the triglycerides are the three main areas that I see omega-3s having solid research around.

Emma: Yeah, and we are going to deep dive into some really fascinating and interesting studies and research today to get some good clinical tips for myself and everyone else that's listening. 

But one of the main risks to the quality of omega-3 is oxidation, which you touched on before, and an estimated 20% of fish oil products have excess oxidation levels. And the question is, does the oxidation occur at the time of manufacturing? Does it occur during transport or while in fact it's sitting on the shelf in a health food shop or a supermarket under bright lights. And the thing is we know that quality matters, and it can mean the difference between a patient reaching a therapeutic dose or not. And all the right criteria can be met by the manufacturer. But as clinicians, how do we try and ensure that oxidation doesn't happen?

Kristina: Yeah, it's really hard. I mean, you can have that third-party tested seal. It’s really somewhat trial and error in finding the companies that you like that are really committed to reducing as much of the variability as they can like having a darker glass packaging or just complete darkness for their pills. And I will say fish oil processes are not my expertise, so I want to put that out there but, from what I understand, a big area where the brand and their quality processes is important is that encapsulation process.

I think all the oils are tested after they've... Like you've explained when they're in the barrel still and when they go from barrel to encapsulation, that could be more different across brands. So, that's where that brand quality is something that you have to trial and error that.

The other way that we think that you can really find out if your supplement is quality is to trial and error on yourself and test your omega-3 status in your blood.

Emma: Yeah, good point.

Kristina: Take the capsules for three or four months and then retest. It should go up, and if it doesn't, which we've seen, then you don't have a quality supplement or it's not working for you. The other thing is the age of the supplement's really important. I think you usually do some years as the shelf life of fish oil. So, the fresher it is, the better it is with these oils, and so that's also something to maybe look for.

Emma: Yeah, and I think, as clinicians, we need to be asking questions of companies, asking them specific questions. Go to the GOED website, have a look at the information there, and be asking those really pointed questions towards the companies that you do use for supplements because, on a cellular level, we want to be affecting change, so we've got to ensure that the product we're using is high quality.

Kristina: Yeah.

Emma: Yeah, I think it's really interesting. You know, contamination is also an issue to be considered. I was reading a really interesting 2017 study that showed that rats fed fish oil that contained persistent organic pollutants developed polyps on their colon. So, the transparency regarding where the fish oil is sourced from and screening for contaminants, I mean, we can be asking these questions of our suppliers.

Kristina: Mm-hmm. Yeah, it's definitely scary. Like, it feels scary and I think to some extent, there is rationale beside behind that. But the other, to some extent, it's overblown. So, for one example fish and seafood have polychlorinated biphenyls, PCBs, and that's something that people are worried about. But it's also present in any animal meat that has fat, so a full fat dairy, beef that has fat. It's actually typically in higher amounts  in those other foods that we eat all the time, at least if you choose to eat meat, we often eat a lot more of those. So, just targeting that toward seafood I don't think is fair, and I think it just adds to some of the fear around seafood that we have.

And the other thing with the mercury levels is at least in the U.S., the majority of the seafood that is most commonly consumed has much, much lower levels of mercury than even our very conservative toxic targets. You'd have to eat pounds and pounds of salmon a week to be able to meet that toxicity level. The one that might be on the edge is I think it's albacore canned tuna. And that's just recommended just have that once a week instead of every day kind of thing. So, that's just kind of on that.

But I did look into the study that you mentioned, and this is something that happens a lot especially in the animal studies where they're trying to see an effect is they're giving super physiological doses. So, I think they're saying the rats are fed a diet of 15% corn oil or cod liver oil or the POP fish, and that is unattainable in the human diet. So, typically as a per cent of calories, the omega-3s are, 1% to 2%, and that's for ALA, EPA, DHA, any omega-3 as the recommended. And EPA and DHA are 10% of that. So, they're at 0.1% to 0.2% of our calories. They're in doses kind of like a vitamin or a mineral. We think a gram of that a day is a lot, and you think about all the grams of fat you eat in a day.

So, this study I would not take and worry about because it's not physiologically real. We don't eat these. We don't eat corn oil on that amount. It's far beyond what we would eat.

Emma: Yeah, and look, interestingly, there's more and more people that are choosing not to eat animal products for whatever reason.

Kristina: Correct.

Emma: You know, the Marine Stewardship Council is a global non-profit organisation and their thing is to address the problem of unsustainable fishing and to safeguard our seafood for the future. But looking at vegan alternatives to marine-based omega-3s, a review that I've read stated algal oil does in fact increase plasma DHA. And I know you do a lot of work in this testing space. Can you give us any insight into how effective you think algal oil is and what kind of doses are needed to match those marine-based omegas?

Kristina: Yeah, this is a great question. The algal oils are the same EPA and DHA that we get in the fish oils. They have the algae that the fish eat, and they feed them sugar and they make the omega-3s. That's what they do. So, it's the same response that you see from a fish oil. It's just, milligram per milligram, the DHA from the algal is the same as fish oil.

So, as far as dosing goes, technically if you're going to try and give, let's say, a 1 gram EPA and DHA from fish oil. You could aim for 1 gram of DHA from algal. But the problem I would say, in reality, is the algals are still quite a bit more expensive...

Emma: Mm, they are.

Kristina: ...to get that high of a dose. And so if you're going a vegan straight algal DHA, I usually don't aim as high for the dose to the blood level. And that's a couple different reasons. 

One is some of what fish oils are doing I feel like are buffering us against some of our poor dietary choices, and vegans tend to take away a lot of the negative dietary choices. Not all vegan diets are perfect, but just having that level of vegetables happening does a lot of good. And so, for most vegans, we did a study and they were averaging about just below 4% omega-3 index, and that's typically when we talk about higher risk for heart disease and that's kind of the undesirable zone.

Emma: That 4% blood level, that was without supplementing, that was food only?

Kristina: Without supplements.

Emma: Right. Okay, got it.

Kristina: Yeah. So, even if you're not eating fish, there's omega-3 in your body. Your body's going to make some amount. But then they did supplement the people with algal DHA, and they were able to get their levels up just like anyone else would on a supplement. 

But in clinical practice, I see 6% as a good intermediate target, especially if what it takes to get to 8% is usually over a gram a day for most people. And to do over a gram a day, an algal DHA could be very expensive and so being that moderately high level instead of the full 8% for a longer period of time, if that's better for the cost of everything, I think that's a good target for vegans.

Emma: Yeah, I love that. I think that's a really balanced approach. And we're going to deep dive into some research on pregnancy and prenatal health. And of course it depends on what's going on for that person, but I think to aim for a 6% blood level of DHA for vegans, that sounds really sensible. You're only trying to bump it up, on average, 2%. So, hopefully that's not going to need a bucketload of supplements for that. So, that's actually really insightful and good news.

Now, if you were choosing a fish oil supplement, what's your criteria? I mean, what boxes does Kristina need to tick to say, "Yes, I'm happy to prescribe this for my patients"?

Kristina: Mm-hmm. Yeah, this is a super personal decision, because the most important thing is something that people are going to take for a long period of time.

Emma: Absolutely, yes.

Kristina: And so it needs to be the right...price is kind of important to some. If it's a capsule, how big? How small? Can you go liquid? Those kind of habitual things that we don't really think about, that's a really important bucket to take seriously, because it might be expensive or hard to swallow, and they'll just kind of stop taking it.

Emma: Exactly. That's right. Compliance is everything.

Kristina: And they don't want to tell you that it's just because it's a bigger pill than I like, but that's so important. 

So, that's important and then the other side more technically the main things are dose, form of omega-3s, and when you take it, like if you're taking it with food is also really key. So, the dose and the form are really key in how it's going to affect your blood levels. For me, targeting blood levels is what I like to do. So, if you eat a ton of fish, you might not need a supplement, because that's what testing your blood levels does. If you're a pescatarian, if you eat kind the Japanese-style diet, people definitely have an 8% on a natural fish-heavy diet.

Emma: Yeah, okay.

Kristina: If you're not, if you're kind of between, most people are eating some fish and then supplementing. And so for me the dose is the most important thing. We've done studies on this to show that going from 4% omega-3 index to 8%…

And I should just quickly define the omega-3 index. It's the amount of EPA and DHA in a red blood cell membrane as a per cent of total fatty acids. And it's a really good marker of intake also really predictive of a lot of health outcomes. And so 4% we see is a standard Western level low fish intake and then 8% is that's, kind of, more normal in high fish eating populations like the Japanese or people who do supplement. And so to go from 4% to 8% takes about 1,400 milligrams of a triglyceride-based supplement, which is about 2 grams of an ethyl ester base.

So, it's basically the triglyceride-based supplements are a little bit better absorbed. You have to take a little bit lower dose typically to get to the same blood levels. And this is what we found in our paper. And so the ethyl ester forms are the first pharmaceutical omega-3s where they really were able to concentrate them. The issue is, for some people, there is an absorption issue for the ethyl esters, especially if they take it on an empty stomach or with a low fat meal.
So, I've counselled people and they've taken a really nice product, great brand, healthcare provider supplement brand, but it's an ethyl ester product and they were taking it on an empty stomach. And she did it for a year where she was testing. She increased her dose from 1,400 to 2,000. Still stayed about 5% omega-3 index. And she finally called me and I was like, "When are you taking it?" And she said, "I'm taking it in the morning." I said take it with food, take it at night, anything. And then she started to do that and her levels went up. So, you can waste a lot of money and time if you don’t check.

Emma: Well, I think this really points to us that we need to be covering basics before we get fancy, and we need to be making sure that our patients are taking supplements at the right time and not taking them with other things that might interact with their absorption. So, cover the basics is the first step and then aim for around 1,400-1,500 milligrams, EPA, DHA a day for an average.

But let's look further into some research. Now, there was the UK Biobank. It's a population-based cohort of around 500,000 people aged between 40 and 69. And at baseline, 32% of these people were taking fish oil. So, researchers have studied the epidemiological data, and there've been some really significant outcomes. Fish oil supplements are associated with a 13% lower risk for developing dementia and an 18% lower risk of developing diabetes. Now, how important is epidemiological data like this? Can we actually take that data, extrapolate it, and use it to help inform our clinical practice? Can we do that?

Kristina: It's probably a bit of a jump to go from epidemiology to clinical practice, but it's a really amazing database for research. And we actually at OmegaQuant and then the Fatty Acid Research Institute or FARI, which is a non-profit that we support, that Bill Harris, who started OmegaQuant, started. So, they're over there doing research, and they have gotten comparison blood from the UK Biobank, tested it against our method of fatty acid analysis. They have a method of fatty acid analysis. We've found a correlation and so now we are publishing, I think we have one paper published and then many more coming on the UK Biobank using blood levels instead of reported fish oil. 

Reported fish oil intake, anytime it's a self-report, there's a level of variability. People may report, "Yeah, I take fish oil, but I take it once every six months when I think of it." There's a huge amount of variability in what that means to somebody, and there's no information on dose of course and all those.

Emma: Yeah, and whether they're taking it on an empty stomach first thing in the morning. All of those things.

Kristina: Exactly.

Emma: Kristina, this is what I'm excited about, because if you can correlate the blood levels from the UK Biobank, then perhaps we can more likely extrapolate that information that that reveals.

Kristina: It gets closer. It's like a big step closer.

Emma: Yeah, great.

Kristina: And it's such a huge database, and it's a great representative sample because that's another huge issue in our smaller research studies is that it's just not representative. There are certain people that will sign up for a study and certain people who won't, and that kind of bias is very, very hard to tease out. And so when you have these huge studies, usually you sacrifice specificity and control, but it's huge data.

So, we've done... The dementia has been corroborated in other studies using blood levels. The developing of diabetes with the fish oil users, that's a little bit more... I'm a little bit more suspicious of that finding, because it hasn't been overly strong in the clinical research, giving fish oil and what it does to insulin and glucose metabolism. So, it could be a signal that people who are taking fish oil are also doing other healthy behaviours.

Emma: True.

Kristina: And that's pretty typical in the big data studies. So, that's where the blood levels really come in, and they just cut through all the noise. We control for all the other habits that we can, and then hopefully we have something that's very much tied to actual amount of omega-3 in your body and what it's doing for health.

Emma: Yeah, exactly. And look, talking about dosing, a few years ago, practice guidelines were released from the International Society for Nutritional Psychiatry about omega-3s for major depressive disorder. And these guidelines recommended a 2 to 1 ratio of EPA to DHA and a net daily EPA of 1 to 2 grams. As a clinician, it was really great to see that they acknowledged in these guidelines that the quality of the supplement can affect the therapeutic activity. And I think this is one point that we all agree on and we all explain to our patients, but what are your general recommendations on dosing in this space?

Kristina: Yeah, it's a really interesting study. It's one of the few clinical groups that actually are getting into the weeds on the omega-3s and giving really specific dosing. So, it's super helpful. 

It's also interesting now that we have been able to have pure EPA or pure DHA supplements and being able to control the ratio of the two in supplements fairly easily, we’re just at the beginning of figuring out for each different kind of health outcome what is the EPA or DHA that's better? Do we little want a little more EPA or more DHA? 

So, there's a lot left to be learned, but in the psychiatric space, a meta-analysis showed that a high-dose EPA was really effective and really quickly effective on I think it was mostly depression symptoms…

Emma: Yeah.

Kristina: …more in the area of mood, then cognitive decline, that area, EPA has been shown to be more effective. And then in the pregnancy space, DHA has been shown to be more effective.
And so I end up, if it's just a general person, I want a mix of EPA and DHA. I don't care too much if it's super high EPA or super high DHA or just a nice balance, but if the overall dose is high enough, that's what I'm concerned about. 

Emma: Yeah, and I think one thing is for sure is that we are just at the tip of the iceberg on everything to do with omega, because I feel like we've been saying this for so long now, but the more we're learning, the more we realise we don't know. It's so true. 

I want to take a look at the VITAL study. This, again, was a population-based study with over 25,000 people that showed that the subjects who had the lowest fish intake were the ones who received the most benefits from taking omega-3s. So, this particular demographic had an overall reduction in their all-cause mortality and a 19% reduction in major cardiovascular events. In your opinion, I mean, who is most at need of omega-3s?

Kristina: This is very typical, I think, in a lot of the omega-3 research is the people who benefit the most are the people who come in with the lowest blood levels of omega-3. They're "deficient." And so of course, as they're somewhat deficient in that nutrient, providing them that nutrient at a good dose should have biological effects. For people who aren't as deficient, that change is not as dramatic and you might not see an effect. And we'll talk about this later in this talk with the pregnancy stuff because there's some very clear data there.

But with the VITAL, when I saw those subgroups, I just kind of think, "Well, duh. Of course." Of course it's people who didn't eat fish and that correlates to low blood levels. And giving them that nutrient that is missing in their diet, it's appropriate. It's supplementing their diet where it's deficient. And so I think that it makes perfect sense, and I think it makes perfect sense that people who already had higher blood levels didn't experience as much of a benefit as well. 
So, that's also very important to keep in mind when we look at research studies. Have they been measuring blood levels or at least fish intake and supplement use at the beginning of the study and analysing data that way?

Emma: And this is an interesting point around setting expectations when we're working with our patients. If we know that somebody is already eating fish a couple of times a week, eats a lot of nuts, seeds, leafy greens. The expectations around what a fish oil might do for them is going to be very different to somebody who is not eating any fish and is not eating those other foods, so that then we can actually explain to our patients this is why, this is what the research shows, and this is what we can expect by giving you this dose. Being specific around the expectations I think is so good when we're dealing with our patients and their expectations.

Kristina: I think that's essential because if they're taking it or taking a little more above their diet and they don't feel anything, a lot of times people don't feel the omega-3 change. Sometimes they do, but if they're very deficient, they do usually. If they're not so much, it doesn't feel that different, and then they might just stop taking it or they might just stop... So, like you said, the expectation setting is just really important.

Emma: Yeah. Now, a fascinating study that came out in October 2022 looked at the relationship between red blood cell omega-3, markers of cognitive decline and brain imaging in middle-aged adults. And there were over 2,100 subjects with an average age of 46, and outcomes were that the subjects with higher levels of omega-3s had a larger hippocampus and better abstract reasoning. And the researchers pointed out epidemiological and intervention studies suggest omega-3 may be most beneficial to preserve brain health from early midlife just before the onset of moderate cognitive changes.

Now I have to give you this insight. I'm about to turn 49. And when I saw the age here, 46, I thought, "Thank goodness I'm already taking my fish oils." But ideally, when should our patients start taking fish oils to protect against cognitive decline? Maybe they have some family history that they really want to work on. Tell us a bit more about that.

Kristina: My first rule is, if you're low in omega-3s, you're going to benefit from omega-3s. My second one is that you need to have them onboard before the health events start happening.

Emma: Okay.

Kristina: The strongest research is showing that people who have higher levels of omega-3s throughout their life and then 10 years later, they're less likely to have any of the big things—heart attacks, strokes, issues with cognitive decline, all of that. It's having the omega-3s in your body to deal with the small inflammatory events that are happening that turn into the big ones.

And that's your question about preventative versus therapeutic. I think this is huge. Omega-3s are so much more powerful probably at lower doses as a preventative if you’re taking it, basically if you have a good amount of omega-3s in your body throughout your entire life. It's really the lifespan at this point and trying to use omega-3s as a therapeutic after something has happened, after a heart attack, after cognitive decline has started, you're going to have to use a higher dose, and you're probably going to have poorer outcomes. You might have a little bit of improvement, but you didn't completely prevent something from happening.

So, I think for me that's where I'd rather have more people have a moderate omega-3 like a 6% omega-3 index over the course of their life than have a 4%, have an event happen, they're up at 8%, they're up at 12%, but then they drop down because it takes so much to get there. That moderate level consistently over your life is really beneficial.

Emma: Yeah, and I think that was an interesting point. So, from that preventative model, fish oils really shine in this space of lifespan and health span at lower doses for a longer period of time, rather than higher doses at a latter point in life. I feel like that is pure preventative medicine there.

Kristina: It is. And it's more accessible through diet. It hits more closely to the fish recommendations that we have, and usually it's two or three servings a week. Make sure it's got some fatty fish. And the epidemiology on people who eat seafood is very strong because it's consistent. If fish is part of your cultural daily life, it's not like, "Oh, I have to remember to take a supplement." It's like, "This is just what I'm eating."

Emma: Yes, exactly. It’s a habit.

Kristina: Yeah, so it's easier to hit 250 to 500 milligrams, which is often where the recommendations come, and that's kind of that lower bar. If I'm trying to treat someone and I'm giving them 250 to 500, I'm not expecting to see a difference in a short time because it's kind of a low dose. So, that's that difference of, "Well, if I'm trying to treat you, I'm going to give you one or two grams at least so you feel something and because we're trying to play catch-up now." But on a public health level, those recommendations I think can be lower, but then it confuses people too because...

Emma: It does.

Kristina: ...it's two different things.

Emma: Yeah, interesting. 

Let’s move to a U.S.-based paper from 2010, which assessed the impact of modifiable risk factors and the number of deaths across the U.S. population. And the mortality effects of low dietary intake of omega-3s were estimated to be 84,000 people annually with the main causes of death being ischaemic heart disease and stroke. 

Now, interestingly, if you smoked and then took omega-3s, your risk for disease was the same as non-smokers who were not taking fish oils. So, how do you think that omega-3s reduce all-cause mortality? I mean, we've talked about the inflammation side of things, which I think is the crux of it, but any other mechanism on the all-cause mortality front you can think of.

Kristina: Yeah, I think this kind of study, we have seen a couple of examples of the same pattern where omega-3s are kind of...it's kind of like the vegan conversation we were having. They're kind of making up for excess inflammation that we're adding to our life. Another really interesting study along these lines was looking at people who lived in areas of high air pollution. And whether or not they had higher or lower blood levels of omega-3s, actually their brain sizes were affected. So, if they had high omega-3 and high pollution, the size of their brains were maintained. But if they were in an area of high pollution and low omega-3, they had shrinkage.

Emma: Wow.

Kristina: So, it's that protective piece where having the omega-3s on board and you're getting hit with these kind of excessive inflammatory events, it protects you. It doesn't grow your brain, but it maintains your brain. We see this also in a lot of the athletic literature where the omega-3s don't grow your muscles, but if you get injured, it helps maintain your muscles, or if you're getting older, helps maintain the amount of muscle you have.

So, I think that is coming back to inflammation, and blood flow is really important. Having good blood flow is similar to some of the benefits of exercise. It's just getting that blood going through your body in an easier way, I think helps all of your systems. And so those two big areas of inflammation and blood flow to me are probably the main things that are helping us live longer and better when we have more omega-3s onboard. And of course the omega-3s combat some of the excessive inflammation that we might be putting onto our body. But if we can also take away some of that excessive inflammation through just not smoking or if we don't live in a place with high air pollution, the omega-3s aren't as needed necessarily because you've already taken away some of those injuries, basically.

Emma: Yeah, and I love this concept. I mean, inflammation I think, as practitioners, we have this awareness around fish oils and inflammation, but I love this concept that you've referred to a couple of times of blood flow. And I think it's a new way for us to potentially look at omega-3s and how beneficial they are. And it's also a great way to explain their benefits to our patients.

Kristina: Yeah, they affect the endothelial function of blood vessels and how well they... I mean, that's one piece. The other piece is platelets. The other piece that we talk about a lot but we aren't... New research that we've been doing, we aren't finding the things we thought we would, but just the actual cell membrane flexibility is pretty important as it turns out, so red blood cells have to go the capillary. They have to be very flexible and squeeze in. Having just the structure of omega-3s because they're kind of those bigger structures, they're not straight lines like saturated fat, that creates space in the membrane, which creates flexibility and fluidity. And so all of those point to an easier blood flow, and that does it. Your heart doesn't have to work as hard. It gets into your brain, but good blood flow is good for everything.

Emma: Yeah. And just the cellular nutrition side of things. When you have superior blood flow, we know that our cells are going to be bathed and nourished in more nutrients. So, I feel like that could be... I'm sure somebody out there is doing research on that cellular nutrition changes in relation to this, but it'd be fascinating to know more about it.

Now let's shift to an area of expertise for you, which is omega-3s before, during, and after pregnancy. Omega-3s are critical for the rapid brain development and the body during that first 1,000 days of life. Let's first look at prenatal omegas, then move to pregnancy, and then this fascinating area of breastmilk omegas. 

Now I know you recommend a prenatal DHA red blood level of 5% and generally about 20% of women in childbearing age will have that level of DHA. And your data shows that if a woman eats fish twice a week, her DHA levels are around 5%, as you've mentioned, and that supplementation can increase DHA levels by 2%, thereby getting closer to the 8%.

Now a little study, a small study you did, showed a dose of—I was really interested in this—only 200 milligrams of DHA per day increased red blood cell DHA significantly in non-pregnant and pregnant women but not as much in breastfeeding women. Now why do you think that was so?

Kristina: Oh, this is such an interesting study. It was a study that was done at Cornell University, Marie Caudill's lab. They have done so much great work on choline in pregnancy.

Emma: Oh, right.

Kristina: And that's what the study was looking at. It was looking at two levels of choline, and they had three groups. They had a non-pregnant women of childbearing age group, pregnancy group, and this was, I believe, the third trimester, and then they had women who were breastfeeding. I would think they were within 10 weeks of postpartum at least. It was pretty close to when they had given birth.

And so they were testing the choline levels that everyone was getting 200 milligrams of DHA. And so we saw that, and we were interested in what does 200 milligrams of DHA do to blood levels, because we didn't really have that. So, we asked them if we could have some blood, they did. It was great. We had a great collaboration with that group. And so that's what we published here.

And 200 milligrams of DHA is a low level, but it's kind of a standard recommended level for pregnancy if there is one. Current recommendations are... technically they recommend that pregnant women have 200 milligrams of DHA extra a day on top of what they assume is 100 milligrams a day. But that assumption is probably double. It is double of what women actually are taking in on average of DHA. So, the 200 is very commonly found. And often if you get a prenatal supplement, it'll be 200 DHA.

So, what we found was that 200 amount was enough to take most of these women, their DHA levels, not EPA and DHA, but just their DHA levels up to above 5%. The pregnant women actually already were at 5%. They increased. So, the women who weren't pregnant and the pregnant women, they were taking in the DHA, and it was going into their own bodies, their own red blood cells. They were absorbing it and integrating it. 

The breastfeeding women, however, they took the same dose, and their levels didn't move, but their breastmilk levels of DHA did. So, we measured the level of DHA in breastmilk, and that's where all the DHA went during lactation, which was fascinating.

Emma: Yeah.

Kristina: So, the DHA, it gives preferentially and during pregnancy and during lactation, as much DHA as possible, is going towards the foetus and the infant. It's just programmed that way. It's so fascinating.

Emma: Yeah, it's quite mind-boggling, isn't it? I mean, how our bodies innately will prioritise that nutrient to be in breastmilk for the development of our babies. It's quite fascinating. 

So, does that mean that pregnant women or breastfeeding women should be taking more DHA? What are your recommendations in this space?

Kristina: In this space, again, I tend towards the blood levels because I don't feel like... I mean, one size doesn't fit all.

Emma: So true.

Kristina: Generally, I think if you're a woman who wants to get pregnant, eating fish two or three times a week is a great thing to do. And that gets you around 200 to 300 milligrams a day of DHA. And so that matches that recommendation well, and there's a lot of great evidence that that's a really good level of seafood to consume pre, during, and post-pregnancy, so if you're into seafood... The other big thing that I don't know if it's the same in Australia, but in the U.S., there's a big fear of fish during pregnancy.

Emma: I would say the same. Yeah.

Kristina: Yes, so basically due to when we didn't know as much about what the mercury in fish could do to a developing child, out of an abundance of caution, and the U.S. Food and Drug Administration and then Environmental Protection Agency put out warnings about mercury to pregnant women, and that's continued to this day where “If there's even a chance that I'm going to affect the cognitive development of my child, I'm not going to eat seafood," is really I feel like where people are at.

The problem is the research says almost the exact opposite, and that eating no seafood is the most detrimental to cognitive development compared to eating seafood. And part of it is seafood is just the perfect package of brain nutrients. Fish is the only natural source of EPA and DHA if you're not supplementing. Choline hugely important and not in most prenatal supplements because it's big. It would make the supplements really big or you have to take a lot of them. But it's important and it's in fish, also in eggs and other foods but also zinc, copper, selenium, all these micronutrients, it's a great source of protein.

So, when you're not getting the seafood in your diet, the biggest one is that DHA, because you're not getting it anywhere else. It’s not naturally found in other things besides seafood. So, if you're not going to have seafood, then you do need to supplement. And I think for just a non-complicated population, 200 to 300 milligrams a day, if you're taking that over a long period of time, that is going to get you to 5% DHA. It's going to get you to maybe 6% of the omega-3 index. And that's pretty good. That's a good baseline. If you want to get to 8%, that is probably going to give you even more benefits, but the most benefit happens at getting out of very low levels, which is over that threshold. And then I think the rest is kind of gravy. 

But to me, if everybody took 200 to 300 milligrams of DHA a day before getting pregnant, I would take that over a few people taking 1,000 milligrams during pregnancy. But if you do want to see a big effect, and we'll talk about this, if you're very low and test and you find that during pregnancy, you do need to take a high dose, you need to take 1,000 milligrams to catch up during pregnancy and to affect risk of pre-term birth.

So, generally 200 to 300 is fine. Taking a normal fish oil supplement is fine. You could take a gram a day normal fish oil of EPA and DHA, and that's going to cover your DHA needs. And it's not going to hurt. So, again, it depends on how much a person wants to supplement and how much they can handle if you're pregnant. You can't necessarily take a supplement and keep it down, you know?

Emma: Yeah, yeah.

Kristina: So, there's all these other things.

Emma: Yeah, but I think that's a good the synopsis really is that prenatally before falling pregnant, if a woman can eat fish two or three times a week, then she's going to be getting around 200 to 300 milligrams of DHA a day, which from all of your research and experience equates to around a 5% omega-3 index so that's covering...

Kristina: 5% DHA.

Emma: DHA, sorry. Thanks for that.

So that's definitely covering the basics, and it's good for us to have that solid awareness. But if she's not eating fish, then we have to move towards the appropriate supplement at that point. 

So that's prenatal. Now the nutritional requirement for omega-3 fatty acids increases in pregnancy, as you mentioned, and it is required for all three trimesters. I was reading a 2018 Cochrane review of 70 randomised controlled trials involving just over 19,000 pregnant women. And key findings were that omega-3 supplementation during pregnancy was associated with reduced preterm births, less perinatal death, fewer neonatal care admissions, and less risk for low birth weight. 

Now, as a practitioner who works in this space, anything that does all of those things is mind blowing, and we need to be aware of this and our fingers on the pulse with this. But what are your dosing recommendations for omegas during pregnancy itself?

Kristina: So this paper's so important, and this was spearheaded by people at the University of Adelaide, you guys in Australia. Bob Gibson and Maria Makrides' group has been the absolute leaders in this, and they are implementing now in South Australia with testing for omega-3s in pregnancy, and just hats off to them.

So, this paper actually inspired us to look at DHA blood levels specifically and pregnancy because these results are so rare to see. And this study, it was a 42% reduced risk of early preterm birth in women who were taking omega versus not in pregnancy. We never see that kind of data when you have these many studies with so much variability in them. So, really strong outcomes here.

So, around dosing for this, there's definitely not enough doctors recommending omega-3s in pregnancy. At least here in the U.S., it is not happening on a large scale at all. And if you're just giving a general recommendation when you're first meeting with somebody and you need to get a prenatal with folic acid, you also need to get a DHA source, at least 200 to 300 milligrams in that. My dream would be for us to test the DHA levels in these women. And then if they're at 5%, I say keep doing what you're doing and make sure you're getting 200 a day, so either you're really eating fish or get a supplement on board. If they're less than 5% DHA, I'm telling them to get 1,000 milligrams of DHA and high-quality as soon as possible.

And I think we're going to talk about this, but a study done in Kansas City at the University of Kansas Medical Center with Susan Carlson, they compared 200 milligrams a day to 1,000 milligrams a day of DHA with the outcome of early preterm birth, which is before 34 weeks, pre-term birth is before 37. So, this is really targeting the earlier births that have the higher impact on quality of life. And so what they found, comparing those two groups, was that the 1,000 milligrams was more helpful, or reduced risk for early preterm birth primarily in women who came in with a blood level less than 5% DHA. 

Emma: Right.

Kristina: Women who came in above 5% DHA at baseline, it didn't matter if they took 200 or 1,000. They had the same rates of preterm birth in that group and it was low. The group that did the worst was the women who came in with a low blood level and got 200 milligrams. 

So, this is where I think it's super important, because the difference between 200 and 1,000 is pretty big when it comes to DHA. And so this is where it's like, yeah, we could tell everyone to take 1,000 and that'd be super. But the reality of that is also like you might lose a lot more people. I need more people to just be on 200 because they're more likely to take it if it's one pill versus five.

Emma: Yeah, that’s a good point. Yeah.

Kristina: So, that study really told the story so well to me and the point where the people who are lower need more and they need it more than what you naturally need because they're super low and deficient.

Emma: Yeah, I read a lot of papers, and it's not often that I read one that really hits me and goes, "Wow, this is going to change the way I practise," and that one really did, that if a woman had a DHA level of below 5% and she was given 200 milligrams of DHA daily compared to 1,000 milligrams, she was twice as likely to have a preterm birth. I mean, we can profoundly change outcomes for our patients based on such incredible data like this.

Kristina: Yeah, and there's nothing else around preterm birth that I know of that is preventative. And there's so much good safety data on omega-3s. It's just such a no-brainer and it's just not being done. So the next step for a lot of the people who have been in this research field like Susan, and Maria, and Bob, they are in implementation mode now.

Emma: Right.

Kristina: They're like, "We've done these studies. We need this to be used." There's the cost-benefit ratio analysis. It's like, there's no comparison. One preterm birth in the U.S. is on average $50,000…

Emma: Wow, okay.

Kristina: …with the NICU. I mean, it's absurd and not to mention the quality of life, the potential prevention of having certain issues due to excessively early preterm birth. And we can do so much to make up, like the NICU processes. We have such great, great medicine to keep the tiniest babies alive, and thriving, and doing well. But if we can prevent the early birth… They are growing. They are developing every day in that third trimester. They're getting so much nutrition from mom and so many important things that just the more we can keep them in the womb, the better.

Emma: Yeah, absolutely. And it's great to hear that the implementation phase is starting because we really need every pregnant woman in the U.S. and Australia to have this information and to be working preventatively in this space. 

And, look, I know you've done a heap of work with levels of DHA in breastmilk, but I would love any clinical insights in this space because from what I know and my colleagues, nobody's really testing breastmilk and DHA. It's not something that we are familiar with, and as a pioneer in this space, what can you tell us and teach us?

Kristina: Yeah, so the breastmilk, it's just a continuation of what's happening in pregnancy. So, the placenta is preferentially pulling up DHA for the infant to develop their brains and their eyes and everything. It's very, very important for development. Breastfeeding is the continuation of that. So, that's their source of DHA after they're out of the womb.

And then formulas now have DHA and arachidonic acid as well. But that's their source, and their brains are being actually built and DHA, it's just, they need it. They need it to build the brain. So, it's just really an important nutrient. So, the DHA and breastmilk is really just more of a nutrient level test than a strong connection to outcomes. 

So, when I was looking at this breastmilk stuff, it was really hard to find studies that were just looking at breastmilk and hadn't also supplemented during pregnancy. It's hard to split out this timeframe of pregnancy and lactation. But when I was looking at it, the breastmilk responds really well to DHA and to EPA, but DHA is what's in there mostly. 

So taking, again, it's that 200 or 300 milligrams a day is what's currently recommended. Breastfeeding, actually, I think the needs might be higher than pregnancy weirdly enough, and I think it's because you're outputting so much, so many calories, so much fat, and all the DHA is going in there. There's some studies that have looked at what's the balance of how high does the mom blood level needs to be for her to produce enough DHA to go into breastmilk and her levels aren't being depleted? And it's really around 1% DHA in the breastmilk, which is about an 8% DHA in the mom, which is probably a 10% or 11% omega-3 index. It's high...

Emma: That is significant.

Kristina: ...for it to be at equilibrium. Otherwise, mom is depleting her sources to get enough DHA into the breastmilk or if you're taking something, most of that's going into breastmilk. And so I would shoot for, at the baseline, at least 300. Go higher, take a gram of fish oil, and you're getting 500 or 600 of DHA. Not going to hurt, not going to hurt at all.

As far as the outcomes go, breastfeeding outcomes, when you're changing the level of DHA within breastmilk, there's not a ton of studies that have done this. Some have found some positive outcomes on some cognitive tests in kids, but I just think, in general, it's very, very difficult to study breastmilk and think that one nutrient in the breastmilk is responsible for a full cognitive outcome, because breastfeeding is such an all-encompassing process. There's so much in breastmilk. I also think it's very difficult to measure cognitive tests in little infants.

Emma: Yeah, absolutely.

Kristina: Those are hard. Those are really hard outcomes. Also, in the pregnancy literature, most of the early stuff is around visual and cognitive development because DHA is so rich in eyes and brain.

Emma: Of course, yeah.

Kristina: And if you completely devoid...like in monkey models, primate models, they deprived multiple generations of mums from DHA and then saw major DHA brain and eye issues. And women, we aren't usually fully deprived of DHA. We always make some amount, so we don't see as extreme of that side, but that's where a lot of the research started.
And then they started to notice, "Oh, gestational age is longer in women who have higher DHA." And then the flip side of that, there's less preterm birth. And the preterm birth is a much easier marker to measure than the cognitive development of a child.

Emma: Yes, very obvious.

Kristina: So, these are some of the issues in the research that, to me, I think the breastmilk DHA level is really important. I think being above 0.32% is kind of that low bar up to 1%. Anywhere in there is great. Just get above that threshold, and that would take probably 200 to 300 milligrams to hit that bar and take more if you want higher levels. And it's good for mum. It's good for baby, whether or not it's going to change IQ by 100 points. No, but it's beneficial, it’s a good nutrient to have on board and it's helpful for both mum and baby, but it doesn't have as clear of the clinical outcomes as the pregnancy literature.

Emma: It'd be interesting to see if any research has been done with brain imaging of breastfeeding women with that lower percentage of DHA, comparing the brain imaging of breastfeeding women who have a higher DHA. It probably hasn't been done yet, but that would be so fascinating to look at.

Kristina: That's a really good idea, I think. I think because there's just a huge depletion happening.

Emma: Yes, but how depleted? I work a lot in the postnatal space and women are always saying, "I've got brain fog. I've got baby brain." And it's like, well, is that physically, structurally a thing because your DHA levels have been altered and your brain imaging? Maybe it's actually impacting in that way.

Kristina: It's possible, yeah.

Emma: Yeah, yeah. Now last question for you. We've covered doses of a omega-3s in prenatal and pregnancy and breastfeeding, but just lastly let's just take a quick look at the food as medicine side of things. We have talked fish consumption, but I wanted to talk about a 2019 review on seafood consumption during pregnancy and brain development.

Kristina: This is a great, great paper. So, we were somewhat involved in this as well. Bill Harris was an author on it. This was a paper written, it was really spearheaded by a group called the Seafood Nutrition Partnership, which is a great organisation for you to check out as far as seafood questions go. And they're just fabulous.

So, one of the things in the U.S. is we have the dietary guidelines, and this group came together because researchers in the field of pregnancy, cognition, omega-3s, and on a public health level, they wanted to see the guidelines reflect that we need to support fish intake in pregnancy rather than just say, "Oh, you can eat up to this much before you're causing damage to your baby." No, we need to have this in our diets because it provides these nutrients that are not anywhere else in our diet, that are really important. So, they wanted to make sure and go back to the literature and really take seriously this question about the seafood, and mercury, and contaminants, and the risk-benefit ratio.

And so they went back into it. They looked at all the studies they could find on seafood intake, and pregnancy outcomes, and cognitive outcomes as well. And they found even stronger data than they thought they would, that more seafood intake during pregnancy was actually associated with better cognitive development, better IQ scores in the offspring. And this is despite the fact the women had higher omega-3 intake, they also had higher mercury intake because fish do have mercury. It's just not enough to be having a negative effect, or the omega-3s and all the other nutrients with the fish are just so much more beneficial than the mercury. 

So, the mercury, if we didn't know anything about mercury and you looked at mercury intake and these IQ outcomes, we'd be like, "Oh, mercury is good for your brain." We know it's not, but it's coming along with all of these other really, really great nutrients.

So, this paper is just a great foundational work for the public health message of seafood is great for pregnant women. It's really important. Nothing in life is completely risk-free. There is some mercury in it, but it's just not enough to have the negative impact. Where you're going to have issues with mercury poisoning is not from seafood, it's from excess pollution. It's from really potent contamination of water or something, but not your standard fish that you can get at the grocery store or anywhere. Those fish are just very low in mercury.

So, that was really the reason for the paper, and they were surprised at the findings that they were so strong, and that made them even more like, "We have to get this public health message out, that need not fear fish when we are pregnant."

Emma: Yeah, and I think we've got to keep that holistic framework of remembering that fish is really bioavailable—protein, the choline, I mean, there's so many other nutrients, as you did point out earlier that we have to keep that holistic framework in mind and not demonise something as blatantly as fish is bad in pregnancy.

Kristina: Yeah, and I think even in general, to the vegan question and we have big questions about sustainability of fish and how well we can feed the world with the fish issues we have, but I do worry about cutting out fish entirely and thinking we can supplement our way out of it in some ways. I don't feel like that's a really great solution because there could easily be a lot more going on besides just the nutrients we know about in fish. There's stuff we probably don't know about or just how they come together, how they're absorbed. So, that's where having these kind of personalised levels where we can have a more moderate intake, we don't all have to be pescatarians to get benefits from seafood, you know? So, if we have a little bit more moderate outlook or we eat some seafood and we take some supplementation, we do a combination of both. I just think there has to be more nuance and more appreciation for what we don't know...

Emma: Exactly.

Kristina: ...because there's a lot we don't know as far as nutrition.

Emma: I'll tell you one thing, Kristina, we all know a lot more than we did before this podcast started. I have to say you are a wealth of knowledge in this space, and I was so keen to get you on the podcast so that you could share all of your research, your clinical insights, and your ability to analyse the data in a way that really makes sense to us as clinicians. So, thank you so much for joining us today.

Kristina: Oh, thank you so much. It's really fun to talk to clinicians. And I just have more and more appreciation for what you guys are going through, because you guys see all the outliers.

Emma: Yeah, we sure do.

Kristina: In research, we just average everyone together. Every single person you guys have to see as a person and treat, so I appreciate you being in the research still and having this great clinical approach to it.

Emma: Thank you. Well, thank you so much, Kristina. Thank you, everyone, for listening today. Don't forget you can find all the show notes, transcripts, and other resources from today's episode on the FX Medicine website. I'm Emma Sutherland. Thanks for joining us. We'll see you next time.


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