Natural Medicine Journal publisher Karolyn A. Gazella talked with Kristie Ebi, PhD, from the Center for Health and the Global Environment with the University of Washington. The two discuss Ebi's research using new technology to model growing conditions as they will be in the coming decades if we don't curb climate change.
In this interview, Ronald Hoffman, MD, describes the scientific research associated with essential fatty acids, specifically omega-3 fats from fish oil. Hoffman touches on some of the controversial research and then focuses on the practical clinical applications that have been confirmed in the scientific literature.
Ronald Hoffman, MD, is a physician in private practice of integrative medicine in New York City. He is a graduate of Columbia College and Albert Einstein College of Medicine. Since 1984, he has served as Medical Director of the Hoffman Center in Manhattan. Hoffman is past president of the American College for the Advancement of Medicine. Hoffman is the host of Intelligent Medicine, a nationally syndicated radio program, and he produces the daily Intelligent Medicine podcast. He is a Certified Nutrition Specialist and the author of several books, including How to Talk with Your Doctor (About Complementary and Alternative Medicine).
For more information, visit drhoffman.com.
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Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Thank you for joining me today. Our topic is the utilization of essential fatty acids in clinical practice. And my guest is integrative health expert, Dr. Ronald Hoffman. Before we begin, I'd like to thank our sponsor Carlson Labs. And thank you Dr. Hoffman for joining me today.
Ronald Hoffman: Well, thanks for inviting me, Karolyn.
Gazella: Well, this is a great topic. And I know that you are consistently a food first clinician. So let's start with something very basic. How much fish does a patient have to eat each week to get the benefit of the omega-3 fats?
Hoffman: Well first, let me just say, this is a controversial topic. And especially when it comes to supplementation, but it's generally acknowledged that a fish is healthy. It's beneficial for a variety of reasons in particular for cardiovascular prevention. And usually the suggestion is that people consume 2 to 3 small to moderate portions of oily fish per week to obtain the optimal amount of omega-3s.
So, for example, a 6-ounce portion of wild salmon contains about 900 milligrams of the EPA, and about 1,000 milligrams of DHA. And 2 to 3 servings a week of salmon, in particular, in a setting where you have a low intake of omega-6, which competes with omega-3, would be adequate for most people. There's also some information that suggests that the omega-3s in fish are more bioavailable than the omega-3s that you get from a capsules where it's in isolated form. And there may be other compounds within fish, even certain fish peptides or proteins, which may have a beneficial effect. So you're getting kind of an all round benefit when you eat fish.
Gazella: That makes a lot of sense. Now I want you to remind us, you mentioned heart health, but can you remind us why these omega-3 fats are so important to human health?
Hoffman: Well, there there's so many ways. First of all, fish oil seems to have an anti-inflammatory effect. It works on tamping down pro-inflammatory pathways within the body. These so called eicosanoid pathways. And also, it has a lot to do with membrane fluidity. So fluid membranes help our blood vessels expand and contract, helps the ingress and egress of compounds into our cells, helps nerve transmission. And that may be why fish oils have what are called pleiotropic effects, which means that they work in a multiplicity of ways to help the body. Brain, heart, circulatory system, joints. There may be even an anticancer effect because of its ability to reduce inflammation, which is a trigger for cancer.
Gazella: Yeah. And I think sometimes when a substance such as fish oil and these essential fatty acids have multiple effects, and can do so much good on so many levels, there's almost a tendency to be a bit suspicious. But it seems—
Hoffman: Right. One of the "too good to be true" phenomenon. It sounds like a panacea. So that tends to induce a little bit of doubt.
Gazella: Exactly. So I think that that's when integrative doctors like yourself and our listeners look to the science. So I'd like to talk a little bit about the science as it relates to the practical use in clinical practice. So which conditions in clinical practice will positively and confidently be impacted by essential fatty acid consumption?
Hoffman: Well, let's start with the controversy, which is about cardiovascular health. And this really dates back to studies of Greenland Eskimos, which showed a near absence of cardiovascular disease. And so then that sort of triggered the gold rush for fish oil supplementation because they thought, well they consume so much of that stuff, this is going to protect the hearts of normal folks in the West.
Lately there's been a lot of blow back against that because, for example, the Cochrane Collaborative has ruled that there is no definitive evidence that fish oil supplementation has heart benefits. But I got to say I critique some of those conclusions because a lot of the studies that show no benefit from fish oil are done with very low doses of fish oil supplements, a capsule or 2 of fish oil of unclear quality.
Also, often when we test fish oil for cardiovascular disease, we have people really tanked up on medication. They're on aspirin, they're on statins. Maybe that will blunt the benefit of the fish oil. And also it may be that fish oil is very preventative against cardiovascular disease, and we'll see the benefits if we do a 20- or 30-year study. But if we take very sick people who are near end stage when it comes to cardiovascular outcomes, we're not going to see that taking a fish oil capsule to 2 is going to make a difference.
But the really exciting development on the fish oil front, and I got to give credit to the company that did this, Amarin, which is the maker of a pharmaceutical fish oil, has a come up with a study, the REDUCE-IT trial, which suggests that their very concentrated version of fish oil can reduce cardiovascular disease risks by 25%. Now they were very quick to say by no means does this suggest that fish oil pills are equivalent to our medication. But Vascepa is really concentrated EPA. And so it remains to be seen if supplementary fish oil has that robust effect. In many studies, it came up short.
Gazella: So let's stick with the cardiovascular effects. When you're talking about that Cochrane Collaborative, was that the study that came out late last year that you're talking about that was a bit controversial, and pretty widely publicized?
Hoffman: Right. And with kind of lurid headlines like there was an editorial in, I guess, it was Journal of the American Medical Association, which is "The Last Nail in the Coffin of Fish Oil." It's almost gleefully pouncing on the supplement industry saying that it doesn't work. But by the same token, I'm pretty sure that the self same journals are going to run ads for the Amarin product that's been validated by scientific research.
Another problem with some of these studies is when some of these studies compare fish oil to an inert placebo, which is olive oil. Well that may be a mistake. Because olive oil actually has cardiovascular benefits. And interestingly in the Amarin study, the REDUCE-IT trial, their placebo was mineral oil. And because you had to give a lot of of these refined fish oil capsules in the active group, you had to have a lot of mineral oil capsules. A lot of people were consuming a lot of mineral oil, which some people would say could actually be deleterious when it comes to a cardiovascular health and reducing the absorption of other critical nutrients.
So this is a very fraught area of discussion because some people say, well, fish oil doesn't make a difference. I would say that it may be different strokes for different folks. Some people who are very deficient in omega-3 would obtain a great deal of benefit. Other people are pretty tanked up on dietary fish consumption. So the benefit is not going to be that great. There may be some genetics involved. Also, it may be that if you're consuming a lot of omega-six fatty acids from seed oils, these are pervasive in our western diet. That may blunt the benefits of omega-3s because we look at the ratio of omega-3 to 6 as being an important determinant of health.
Gazella: Yeah, that's a good point. So I'd like to stick on the clinical applications here. There are a lot of doctors that I interview that actually think of fish oil or these essential fatty acids as foundational. And if their patients are not eating enough fish, and they're not getting enough of these in the diet, they automatically supplement even if there's no real clinical application. What's your view in your clinical practice? Do you supplement? When do you supplement? And for what conditions other than cardiovascular may you consider fish oil supplements?
Hoffman: I do believe in that, what you just stated. Which is I think that that's part of, if one's going to construct a [inaudible 00:09:43] series of 4 or 5 supplements that people should take, I think fish oil is right up there. I personally take fish oil. I have my family members taking fish oil. I have my patients taking fish oil. And it's kind of an insurance policy against lack of the requisite amount of fish oil that prevents a variety of diseases.
We see also benefits in pregnancy. A recent study showed that there was a preventive effect against preeclampsia of omega-3 supplementation. That's a bad pregnancy outcome. Also reduces the instance of premature births. There may be some benefits in terms of a kid's ultimate intellectual development, DHA, which is a constituent of fish oil. Docosahexaenoic acid is naturally present in breast milk. So it was only recently that US manufacturers joined the rest of the world in adding DHA to infant formulas. Long overdue.
Also in brain conditions. We look at a lot of neurodegenerative conditions where there's an inflammatory component. These include Alzheimer's, also depression. There are actually some very good studies looking at depression and omega-3 fatty acid administration. Certainly that would be an area of application. Autoimmune disorders, inflammatory disorders, dermatological conditions that are inflammatory, on and on it goes. There's so many different applications.
Gazella: Yeah. Now you mentioned DHA, and often when we think of omega-3s, we do think specifically of DHA and EPA. Now you mentioned the applications of DHA in terms of pregnancy and childbirth. So from a clinical perspective, is there a time when you look to one of these to be emphasized over the other? Can you expand on that a little bit more?
Hoffman: Yeah. And I wish there was a rocket science answer to that. And I've just looked long and hard into the literature over the past few years. And it appears that EPA may be more important as an anti-inflammatory. And many studies suggest it's good for the brain because it reduces inflammation. But also DHA plays a very important role in brain health. It's certainly important in neurodevelopment. Deficiency of DHA is associated with behavioral problems and intellectual problems in kids.
And so it really is unclear. And if someone says it's DHA or EPA as a definitive answer, I would say, walk away from that conclusion. They seem to work synergistically to support health. The question is sometimes ratio, sometimes in certain conditions we might go for more DHA, other conditions we might emphasize EPA. But it appears that they both play central roles, and sometimes in the very self same condition.
Gazella: Yeah. Now, before I leave the topic of the research, because we talked about the controversial negative research that came out late last year, and sometimes bubbles to the surface every now and then. It seems like, and I know you're in the scientific literature all the time, it seems like the more I look at the scientific literature, gosh, there's not a month that goes by where I don't read a new study on fish oil. So in general, are you pleased with the research that's coming out about these essential fatty acids?
Hoffman: Well, the last time I checked, there are at least 20 or 30,000 articles that support the benefits of fish oil for one or another health problem. So when some group like the Cochrane Collaborative comes out and says fish oil is worthless, I think it's a conclusion that ignores the vast amount of evidence that supports the benefits of fish oil.
So, it's not binary. I think that we can't overhype or overestimate the universal benefits of fish oil supplementation. And there are appropriate cautions when we look at some of these big studies. But still, I'm generally supportive of especially targeted use of omega-3 for specific conditions.
Gazella: So now let's dig into some practical aspects. If a patient can't get the omega-3s that they need from diet alone, what dosage or ratio of these fats are typically recommended as a dietary supplement?
Hoffman: Well again, it depends. So for example, for cardiovascular, I'm thinking if people have serious cardiovascular problems, they need higher doses. So that comes to us for the REDUCE-IT study that used 4,000 of EPA, pure EPA to reduce cardiovascular risk. So it kind of depends on what you're dealing with. To lower triglycerides, for example, you need pretty high doses, not just a pill a day, or even 2 pills a day. But for general supplementation, I suggest one of the potent formulations of omega-3 that delivers a high percentage of EPA-DHA per capsule. The 1,000 milligram capsules, not the little teensy tiny capsules, 1 capsule, twice daily for general prevention.
Gazella: So that's 1,000 milligrams twice daily for general. And then what's the upper dose for somebody who may be having cardiovascular issues? Did you say 4,000?
Hoffman: I would say 4,000 for somebody with cardiovascular issues. Now what we have to be a little careful because some people have bleeding tendencies, or who are on blood thinners. And I notice it's very individual because some people taking high doses of fish oil have no problem whatsoever. Others have more easy bruising, or some signs, nosebleeds, that suggest that that is thinning the blood inordinately.
Gazella: Right. And I agree-
Hoffman: And that's a good effect. Ultimately, from a cardiovascular disease standpoint, that's actually a good effect.
Gazella: Right. And I do agree with you, it's a highly individualized approach that each practitioner uses. What about contraindications and safety? Anything else that needs to be discussed regarding that?
Hoffman: There are some studies that suggest that because omega-3 fatty acids sort of tamp down the immune system, as in autoimmune diseases, I love using them in conditions like Lupus and rheumatoid arthritis, that very high doses might suppress the immune system to the point where people are more vulnerable to infections. But I've seen a couple of suggestions in studies that that can be a problem. But I haven't seen it as a practical situation. Just as a potential caution. I would look to that possibly.
Gastrointestinal symptoms limits its use because some people are prone to diarrhea. It's great for all sorts of ulcerative colitis, but that being a GI condition, it's sometimes hard to administer sufficient amounts to get a good effect.
Gazella: Yeah. And the autoimmune conditions kind of caught my attention. So did you say that you use higher doses in cases of autoimmunity?
Hoffman: I do. There are some studies that suggest that as much as 9,000 per day can be beneficial in ulcerative colitis, which is an autoimmune condition. But again, that too has been subject to question. Some study suggests that it's not as helpful as was once thought for UC. But I think it's just reducing the inflammatory cascade is very important in these diseases. So you can really sort of turn around.
It's like using this powerful immune modulators that really target parts of the immune system and knock them out. Well, they knocked the immune system out to the point, the pharmaceutical drugs, where people are vulnerable to infections. And fish oil may be sort of a more gentle immune modulator that kind of turns down the volume on an autoimmune reaction.
Gazella: Yeah. That's good information. So a big issue when it comes to fish oil supplementation is quality. I mean obviously quality is always a big issue. But it seems like it's even more important when it comes to fish oil in particular. Why is that?
Hoffman: Well, there're a lot of issues with the quality and storage of fish oil. Fish oil, as a polyunsaturated fat, is subject to rancidity. So freshness is a big issue. I would look to a big reputable brand that's been around for a long time. I would also look at third-party certification. There are various places that do that. One of them is called IFOS, which is the International Fish Oil Standard program.
There's also the USP and the NSF, the national standards, which give companies a validation that their product is pure and of good quality. You want to make sure there's no flavorings or colorings to bad artificial ingredients. Another issue is sustainability. There's this issue of overfishing the oceans. And one certification is offered by something called the Marine Stewardship Council. Which awards a certificate to companies that farm fish responsibly rather than devastating the environment.
Fish oil should have maybe a faintly fishy smell, but if it has sort of a bigger acrid taste or smell, that's likely that it's rancid. And the other thing is just the potency. You want to look at products that deliver the requisite amount of EPA DHA per capsule. And that has to do with the degree of concentration and molecular distillation that they undergo to deliver active ingredient rather than just fishy extract in a capsule.
You want to look at the presence of PCBs, or mercury. And there should be a purity guarantee. And especially when companies undertake a responsible self-testing, where they test batches of their material, and you can actually request their specs. You just email the company, or call a 800 number, and they can actually give you the specs on the product that you're taking, just to verify that you're not getting harmful amounts of mercury, or PCBs. So those are among the concerns. If you go to a place, and you find a bottle of fish oil, it's like $9.99 for 500 capsules, I mean, it's not very plausible that they're doing adequate quality control.
Gazella: Right. I think that that's a really good point. Now when you're talking about... I want to touch on some of these. Because you brought up a lot for practitioners to think about when it comes to them choosing a high-quality fish oil supplement. So when you're talking about that third-party certification, is that third party company the one that tests for mercury and purity, and things like that? Or is that something that's done in-house by the manufacturer?
Hoffman: I think it's actually responsible companies will test the material on receiving the material. First of all, they receive a big batch of fish oil before they encapsulate it. So they want to make sure that their supply chain is reliable. So they'll undertake pre-testing. They'll also sometimes do an audit. They'll say, "Let's take a bottle of this stuff at random, and let's do random testing and see if what comes out of the assembly line is fresh." I think they might do tests for lipid peroxides, but also free of contaminants.
So it's more expensive to do that. There's no question. But responsible companies that want to maintain a good reputation and deliver quality products undertake that. And that's actually a selling point for them because the consumer can feel they're reliable.
Gazella: Oh, I would agree. And I think for our listeners, they can get the specs of those random testing batches and the third party certification information, that all helps to know that they can—
Hoffman: There's a lot number. There's actually a lot number on the products so that people could say, "Well I have lot number 56328. Can you show me the spec sheet?" And your eyes glaze over when you see these spec sheets. But you can actually see the contamination is like 0.0000000... way below what the EPA, for example, Environmental Protection Agency, would consider a toxic exposure.
Gazella: Here's a random question. I was told once that if you have a fishy burp that that means the product is rancid.
Hoffman: No. I think that's a kind of a misconception. You can minimize the fishy burp in a couple of ways. One is to take what are called enteric capsules, but there's a trade off. A, they're more expensive, and B, they don't contain as much fish oil. Enteric means that they're coated so that they break down lower in your GI track. The fishy burp can be camouflaged also by lemon flavoring, or orange flavoring, or sometimes cherry flavoring.
And also to some extent the fishiness is associated with purity of the capsule. So products that are not highly distilled will have some... it's basically you're smelling the proteins, or the various residues that are not the active ingredient. But you can't really use that as an ironclad way of determining if the product you've taken is fresh or rancid.
Gazella: Yeah. That's what I was thinking as well.
Hoffman: I would not stand by that. And some people are highly sensitive to the smell or taste of fish oil. Some people have GERD or reflux. And they have an aftertaste of many things that they take in.
Gazella: Right. Yeah. Okay. So what's your view on krill oil versus fish oil? Do you have a preference one over the other? And if you do, why?
Hoffman: Well, okay. There's a lot of promotion of krill oil. And it's based on a couple of basic ideas. One is that while krill oil, the actual capsules may contain less fish oil, and some of the capsules are smaller. Those are usually easier to swallow, that's a selling point. That it's more bioavailable. I've looked at the studies that purport to show that and they're very few and far between. They're based on a small number of individuals. They don't really meet the threshold for demonstrating that the claims are really true, that you're going to get more into your system.
The other benefit is said to be that they contain astaxanthin, which is a good thing supposedly. It's an antioxidant. It's got benefits. If you want to take astaxanthin, take it in a separate pill, or just eat farmed salmon. Because farmed salmon is loaded with astaxanthin. It's what they use to make the flesh look red. So I'm not the biggest fan of krill oil. Plus there's also a sustainability issue. It's very aggressively farmed. It's a form of crustacean that supports the whale population. And it's a little worrisome that there a scooping up all the krill to feed a very, very hungry marketplace in Europe and the United States.
Gazella: Yeah, I would agree. I think that sustainability issue is really an important one. I also agree. I don't read nearly as many studies on krill oil as I do on fish oil. The issue of astaxanthin, is there even enough in krill oil to have a therapeutic effect?
Hoffman: Yeah. First of all, astaxanthin is one of those things that has purported benefits, and I think it's on my radar screen amongst beneficial supplements. But it doesn't have as much robust information to support it as some of the more tried and true things like curcumin, and omega-3 fatty acids, and vitamin D, and coenzyme Q10. I think those are real stayer players. And astaxanthin is a little bit in an intermediate stage of credibility.
Gazella: So what do you recommend for your vegetarian and vegan patients when it comes to essential fatty acid supplementation?
Hoffman: Well, they can, I mean there's a couple of ways to go. One is to take flaxseed oil, or to eat a lot of nuts like walnuts and flaxseeds that are rich in omega-3 precursors. But the problem is the human body, and it's variable in its genetic capability. Some people convert very readily, and other people don't convert very well at all.
So the solution then is to get vegan capsules. They're made from algae, and virtually every company that markets fish oils markets products for vegan users. The concentration of EPA and DHA is going to be a little less these. Most of these products skew more towards DHA than EPA because DHA predominates in algae as opposed to fish that you usually deliver more EPA than DHA. But you can go that that route.
I think it's particularly important for vegans to supplement. if you're going to go vegan, you got watch for B12, you got to watch for zinc, you have to watch for your omega-3s, and certainly iron. And then you can frequently be a vegan.
Gazella: Yeah, that makes a lot of sense. Now, we covered a lot today, but I want to make sure that we have covered everything associated with the utilization of essential fatty acids in clinical practice. What further advice can you give our listeners who are either using fish oil in their clinical practice, or want to use it differently, or want to use fish oil more in their clinical practice? What your bottom line advice to them?
Hoffman: Well, I got to say keep your eye on the specific studies that clearly demonstrate the benefits of fish oil. Look at the therapeutic uses of fish oil. I think kind of ignore some of the bold headlines like "The Final Nail in the Coffin of Fish Oil." That's a little overdramatic. That was a JAMA headline last year that gleefully pounced on a study that showed that fish oil didn't make much difference.
And also look to specific conditions. So for example, we're looking at concussions now. A very high dose fish oil in a protocol for concussions has been shown to be efficacious. So, there's 2 aspects. One is the general use. Yeah. Everybody should get some omega-3s. We should certainly eat fish, and perhaps supplement with some omega-3.
But also look at the targeted application of fish oil as a therapeutic agent, not just as a dietary constituent for prevention. But as a molecularly targeted therapeutic agent that deserves a place alongside with our commonly used drugs, medications. It's no coincidence that a companies are now making concentrated fish oil, and selling them as prescription drugs on the pharmaceutical marketplace.
Gazella: Yeah, I think that's great advice. Taking a look at this from a therapeutic targeted perspective in clinical practice I think is really important. I have to say following the research on fish oil, and EPA, and DHA is pretty exciting.
Hoffman: It's a little bit like a watching Djokovic play in the finals at Wimbledon, going back and forth.
Gazella: Exactly. I watched that match. It was incredible.
Hoffman: It's like, well, let's see. Who's on top? Yeah.
Gazella: Yeah. Well, as per usual Dr. Hoffman, this has been great. You've provided us with a lot of information that our listeners can use in their clinical practice. So I want to thank you for joining me. And I also want to, once again, thank our sponsor who is Carlson Labs. So thanks for joining me, Dr. Hoffman.
Hoffman: Thank you very much, Karolyn. Really enjoyed talking to you.
Gazella: Great. Have a wonderful day.
Hoffman: You take care.