Are Some Omega-3 Fish Oil Supplements Better Than Others?

Written by Dr. Steve Chaney on . Posted in current health articles, Omega-3 Fish Oil Supplements

Author: Dr. Stephen Chaney

truth about omega-3 fish oil supplementThe ethyl ester form of omega-3 fatty acids from fish oil has been the industry standard for high purity omega-3 fish oil supplements for many years. It is very stable, easily purified, and well absorbed by the body. What’s not to like?

If you believe some recent advertisements, there is a lot not to like about the ethyl ester form of omega-3s. These ads each claim that their particular form of omega-3s is more natural, better absorbed, and more efficiently incorporated into cell membranes, or some combination of those features. They each cite clinical studies “proving” that their products are superior. These advertisements seem so plausible and so compelling.

However, most of these advertisements come from relatively new companies that are trying to make a name for themselves in a very profitable and competitive product niche. Are the advertisements true, or is it all just smoke and mirrors? Most of these advertisements rate at least one Pinocchio.

However, it is almost impossible to tell you why I consider these advertisements omega-3 fish oil supplements to be misleading without getting a little “techie”, so let’s start with some basic definitions. I call this section “Omega-3s 101.”

 

Omega-3s 101

 

Let’s start with some basic definitions:

  • Free fatty acids (FFA) are long chain hydrocarbons with a single acid group at the end. They are only slightly water soluble. They are important intermediates in metabolism, but they are almost always combined with something else in the body.
  • Saturated fatty acids contain no double bonds, monounsaturated fatty acids contain one double bond, and polyunsaturated fatty acids contain multiple double bonds. The number of double bonds primarily affects whether they are liquids (polyunsaturated) or solids (saturated) at room temperature.
  • omega-3 fatty acidsThere are two classes of polyunsaturated fatty acids that are essential because the body cannot make them. Those with a double bond 3 carbons from the end are called omega-3s(If you think about the Greek alphabet, omega is at the end). Those with a double bond 6 carbons from the end are called omega-6s.
  • When 3 fatty acids are combined with a single molecule of glycerol they form very water insoluble compounds commonly referred to as fats or triglycerides. The proper chemical name is triacylglycerol, which is abbreviated TAG.
  • If one of the fatty acids on the glycerol chain is replaced by a compound containing phosphate and other charged residues, the resulting complex is called a phospholipid (PL). Because these compounds have a hydrocarbon surface that is attracted to fats and a highly charged surface that is attracted to water, they are good at emulsifying fats and are an important part of membrane structure. One phospholipid that is a major component of membranes is called phosphatidylcholine (PC), also known as lecithin.

Next, let’s look at how omega-3 fatty acids are metabolized:

  • The omega-3s in fish oil are primarily in the form of triglycerides, with small amounts of phospholipids. The omega-3s in most omega-3 supplements are in the form of ethyl esters for the reasons stated above.
  • Before the omega-3s leave the intestine they are hydrolyzed to free fatty acids.
  • In the cells that line the intestine the omega-3s are reconverted back into triglycerides and phospholipids and incorporated into special lipid-protein complexes for transport through the blood.
  • Once these lipid-protein complexes reach our cells, their contents are delivered to the cell where they can be stored as fat (TAG), used for energy (FFA), or incorporated into membranes (PL). It is primarily the omega-3s incorporated in cellular membranes that are thought to be responsible for the beneficial effects of omega-3s.

Finally, we should ask how one measures the bioavailability of the various forms of omega-3s:

While there are some nuances that I did not cover, the basic mechanisms of absorption and metabolism of omega-3s are remarkably similar regardless of whether they start out in the ethyl ester, triglyceride, phospholipid, or free fatty acid form. The questions then become, how does one test how efficiently the various forms are utilized by the body and how much do these individual test actually tell us?

  • When we look at what happens in the bloodstream, we need to be aware that we are looking at a combination of two effects – how rapidly the substance enters the bloodstream and how rapidly it leaves from the bloodstream. There are three important parameters we can measure when looking at delivery of omega-3s to the bloodstream:
    • The maximum concentration achieved (Cmax)
    • How rapidly that maximum concentration was achieved (Tmax)
    • The total amount in the bloodstream over time (AUC)
  • When you look at some of the ads touting specialized forms of omega-3s, they are usually based on studies looking at either the maximum levels of omega-3s in the bloodstream (Cmax) or how rapidly those maximum levels were achieved (Tmax). (One suspects the ads may have selectively featured whichever parameter made their product look best). However, the parameter that really matters is the total concentration of omega-3s achieved over time (AUC).
  • Finally, the most important question is how much of the omega-3 is actually incorporated into cellular membranes. Once again, there is more than one parameter that can be measured.
  • One can measure the level of omega-3s found in cellular membranes in a short term study (a few hours) or in a long term study following many weeks of supplementation.
  • The short term studies only measure the rate of incorporation. The long term studies measure the steady state levels attained over time, which is a much more relevant measure.
  • Once again, the ads touting specialized products are usually based on short term studies which are really measuring an initial rate of incorporation of omega-3s into cellular membranes, not on long term studies that measure the steady state level of omega-3s achieved over time.

 

Are Some Omega-3 Fish Oil Supplements Better Than Others?

omega-3 fish oil supplementThere has been a lot of confusion in the literature about whether the form of omega-3 supplements matters. Various studies have been published supporting the superiority of one form or another of omega-3s. Most of these studies have been supported by manufacturers who have a particular form of omega-3s they want to sell, and, as I mentioned above, the parameters tested seem to have been selected to make their supplement look good.  So, are some omega-3 fish oil supplements better than others?

 

Finally, someone has designed a comprehensive study to clear up all the confusion and provide answers that can be trusted (West et al, British Journal of Nutrition, 116: 788-797, 2016). Interestingly, this research was supported by a pharmaceutical company (Vifor Pharma) that does not appear to sell an omega-3 product currently. Perhaps they simply wanted to find out what worked best before designing their own product. What a novel concept!

The authors tested 4 different forms of omega-3 fish oil supplements:

  • Unmodified fish oil containing the omega-3s primarily in triglyceride form (uTAG).
  • An omega-3 supplement in which the omega-3s in the fish oil had been hydrolyzed to free fatty acids (FFA).
  • An omega-3 supplement in which the omega-3s in the fish oil had been hydrolyzed to free fatty acids and converted back to triglycerides (TAG)
  • An omega-3 supplement in which the omega-3s in the fish oil had been hydrolyzed to free fatty acids and converted to ethyl esters (EE)

All 4 supplements contained 1.1 grams of EPA and 0.37 grams of DHA.

The authors conducted two studies:

  • One was a cross-over study where healthy men consumed each of the supplements in random order on different days with 14 days between tests. Blood samples were collected over the next 6 hours and levels of EPA and DHA in the blood and cellular membranes was determined.
  • The other was a long term study in which a randomized group of healthy men and women consumed one of the supplements for 12-weeks and incorporation of the EPA and DHA into cellular membranes was measured.

The results were pretty clear cut:

  • In the short term study there were no significant differences between the various supplements in the rate of uptake, maximum concentration achieved, or the total concentration over time when uptake of omega-3s into plasma triglycerides and phospholipids was measured.
  • The ethyl ester form was less efficiently incorporated into plasma free fatty acids than the other forms as reported in some previous studies, but this is perhaps the least important parameter measured, and there was large variability from subject to subject.
  • In the long term study, no significant differences were seen between the various supplements in omega-3 incorporation into cellular membranes.

The authors concluded: “Together, these findings show that in healthy individuals neither the lipid structure nor the overall fatty acid composition of supplements influence their bioavailability during dietary supplementation, despite the apparent lower postprandial availability [in short term studies] of EPA + DHA ethyl esters compared with triglycerides or free fatty acids.”

What Do These Studies Mean For You?

You can forget all those ads hyping the newest, greatest form of omega-3 fish oil supplements. Objective research has shown there is not a dimes worth of difference between the various forms of omega-3 supplements.

A far more important question is the purity of the omega-3 supplement you are using. Purity of omega-3 supplements is a huge issue. You need to remember that the EPA + DHA supplements you purchase come from polluted fish. Unfortunately, many manufacturers have inadequate purification and quality control standards. In other words, neither you nor they know whether their omega-3 products are pure. You need to make sure that the omega-3 supplement you purchase is made by a manufacturer with stringent quality control standards.

Sustainability is also an issue, so you should choose manufacturers who source their omega-3s in a sustainable manner. There are two comments I will make about sustainability so you won’t be misled.

  • Krill oil is marketed as a more sustainable source of omega-3s. Krill reserves are quite large, but they are not infinite. Krill is also the very foundation of the food chain that supports a large percentage of our ocean’s fish. We need to be very cautious about depleting our krill reserves.
  • Omega-3s derived from algae are also marketed as a more sustainable source of omega-3s. Algae-derived omega-3s have purity issues of their own, but may become an important source of omega-3s once those issues have been resolved.

 

The Bottom Line

  • The ethyl ester form of omega-3 fatty acids from fish oil has been the industry standard for high purity fish oil supplements for many years. It is very stable, easily purified, and well absorbed by the body.
  • However, in recent years, some manufacturers have been claiming that their omega-3 fish oil supplements were better utilized by the body because their supplements contained the omega-3s in triglyceride or free fatty acid forms.
  • Unfortunately, the clinical studies supporting those claims have been supported by the manufacturers making the products. There is reason to suspect that the data has been “cherry picked” to support the conclusions that support the manufacturer’s claims.
  • Finally, an independent and comprehensive study has compared the various forms of omega-3 fatty acids. It found that neither the lipid structure nor the overall fatty acid composition of omega-3 supplements influenced their bioavailability during long term dietary supplementation.
  • A far more important question is the purity of the omega-3 supplement you are using. Purity of omega-3 supplements is a huge issue. You need to remember that the EPA + DHA supplements you purchase come from polluted fish. Unfortunately, many manufacturers have inadequate purification and quality control standards. In other words, neither you nor they know whether their omega-3 products are pure. You need to make sure that the omega-3 supplement you purchase is made by a manufacturer with stringent quality control standards.

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  • Peggy Shearin

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    very, very interesting..

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Latest Article

Should We Use Supplements For Cardiovascular Health?

Posted July 10, 2018 by Dr. Steve Chaney

Are You Just Wasting Your Money On Supplements?

Author: Dr. Stephen Chaney

 

supplements for cardiovascular health wast moneyYou’ve seen the headlines. “Recent Study Finds Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.”  You are being told that supplements are of no benefit to you. They are a waste of money. You should follow a healthy diet instead. Is all of this true?

If I were like most bloggers, I would give you a simple yes or no answer that would be only partially correct. Instead, I am going to put the study behind these headlines into perspective. I am going to give you a deeper understanding of supplementation, so you can make better choices for your health.

 Should we use supplements for cardiovascular health?

In today’s article I will give you a brief overview of the subject. Here are the topics I will cover today:

  • Is this fake news?
  • Did the study ask the right questions?
  • Is this a question of “Garbage In – Garbage Out?
  • Reducing Heart Disease Risk. What you need to know.

All these topics are covered in much more detail (with references) in my book “Slaying The Supplement Myths”, which will be published this fall.

 

How Was This Study Done?

supplements for cardiovascular healthThis study (D.J.A. Jenkins et al, Journal of the American College Of Cardiology, 71: 2540-2584, 2018 ) was a meta-analysis. Simply put, that means the authors combined the results of many previous studies into a single database to increase the statistical power of their conclusions. This study included 127 randomized control trials published between 2012 and December 2017. These were all studies that included supplementation and looked at cardiovascular end points, cancer end points or overall mortality.

Before looking at the results, it is instructive to look at the strengths and weaknesses of the study. Rather than giving you my interpretation, let me summarize what the authors said about strengths and weaknesses of their own study.

The strengths are obvious. Randomized control trials are considered the gold standard of evidence-based medicine, but they have their weaknesses. Here is what the authors said about the limitations of their study:

  • “Randomized control trials are of shorter duration, whereas longer duration studies might be required to fully capture chronic disease risk.”
  • “Dose-response data were not usually available [from the randomized control studies included in their analysis]. However, larger studies would allow the effect of dose to be assessed.”

There are some other limitations of this study, which I will point out below.

Is This Fake News?

supplements for cardiovascular health fake newsWhen I talk about “fake news” I am referring to the headlines, not to the study behind the headlines. The headlines were definitive: “Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.” However, when you read the study the reality is quite different:

  • In contrast to the negative headlines, the study reported:
    • Folic acid supplementation decreased stroke risk by 20% and overall heart disease risk by 17%.
    • B complex supplements containing folic acid, B6, and B12 decreased stroke risk by 10%.
    • That’s a big deal, but somehow the headlines forgot to mention it.
  • The supplements that had no significant effect on heart disease risk (multivitamins, vitamin D, calcium, and vitamin C) were ones that would not be expected to lower heart disease risk. There was little evidence from previous studies of decreased risk. Furthermore, there is no plausible mechanism for supposing they might decrease heart disease risk.
  • The study did not include vitamin E or omega-3 supplements, which are the ones most likely to prove effective in decreasing heart disease risk when the studies are done properly (see below).

Did The Study Ask The Right Question?

Most of the studies included in this meta-analysis were asking whether a supplement decreased heart disease risk or mortality for everyone. Simply put, the studies started with a group of generally healthy Americans and asked whether supplementation had a significant effect on disease risk for everyone in that population.

That is the wrong question. We should not expect supplementation to benefit everyone equally. Instead, we should be asking who is most likely to benefit from supplementation and design our clinical studies to test whether those people benefit from supplementation.

supplements for cardiovascular health diagramI have created the graphic on the right as a guide to help answer the question of “Who is most likely to benefit from supplementation?”. Let me summarize each of the points using folic acid as the example.

 

Poor Diet: It only makes sense that those people who are deficient in folate from foods are the most likely to benefit from folic acid supplementation. Think about it for a minute. Would you really expect people who are already getting plenty of folate from their diet to obtain additional benefits from folic acid supplementation?

The NIH estimates that around 20% of US women of childbearing age are deficient in folic acid. For other segments of our population, dietary folate insufficiency ranges from 5-10%. Yet, most studies of folic acid supplementation lump everyone together – even though 80-95% of the US population is already getting enough folate through foods, food fortification, and supplementation. It is no wonder most studies fail to find a beneficial effect of folic acid supplementation.

The authors of the meta-analysis I discussed above said that the beneficial effects of folic acid they saw might have been influenced by a very large Chinese study, because a much higher percentage of Chinese are deficient in folic acid. They went on to say that the Chinese study needed to be repeated in this country.

In fact, the US study has already been done. A large study called “The Heart Outcomes Prevention Evaluation (HOPE)” study reported that folic acid supplementation did not reduce heart disease risk in the whole population. However, when the study focused on the subgroup of subjects who were folate-deficient at the beginning of the study, folic acid supplementation significantly decreased their risk of heart attack and cardiovascular death.  This would seem to suggest using supplements for cardiovascular health is a good idea.

Increased Need: There are many factors that increase the need for certain nutrients. However, for the sake of simplicity, let’s only focus on medications. Medications that interfere with folic acid metabolism include anticonvulsants, metformin (used to treat diabetes), methotrexate and sulfasalazine (used to treat severe inflammation), birth control pills, and some diuretics. Use of these medications is not a concern when the diet is adequate. However, when you combine medication use with a folate-deficient diet, health risks are increased and supplementation with folic acid is more likely to be beneficial.

Genetic Predisposition: The best known genetic defect affecting folic acid metabolism is MTHFR. MTHFR deficiency does not mean you have a specific need for methylfolate. However, it does increase your need for folic acid. Again, this is not a concern when the diet is adequate. However, when you combine MTHFR deficiency with a folate-deficient diet, health risks are increased and supplementation with folic acid is more likely to be beneficial. I cover this topic in great detail in my upcoming book, “Slaying The Supplement Myths”. In the meantime, you might wish to view my video, “The Truth About Methyl Folate.”

Diseases: An underlying disease or predisposition to disease often increases the need for one or more nutrients that help reduce disease risk. The best examples of this are two major studies on the effect of vitamin E on heart disease risk in women. Both studies found no effect of vitamin E on heart disease risk in the whole population. However, one study reported that vitamin E reduced heart disease risk in the subgroup of women who were post-menopausal (when the risk of heart disease skyrockets). The other study found that vitamin E reduced heart attack risk in the subgroup of women who had pre-existing heart disease at the beginning of the study.

Finally, if you look at the diagram closely, you will notice a red circle in the middle. When two or three of these factors overlap, that is the “sweet spot” where supplementation is almost certain to make a difference and it may be a good idea to use supplements for cardiovascular health.

Is This A Question Of “Garbage In, Garbage Out”?

supplements for cardiovascular health garbage in outUnfortunately, most clinical studies focus on the “Does everyone benefit from supplementation question?” rather than the “Who benefits from supplementation?” question.

In addition, most clinical studies of supplementation are based on the drug model. They are studying supplementation with a single vitamin or mineral, as if it were a drug. That’s unfortunate, because vitamins and minerals work together synergistically. What we need are more studies of holistic supplementation approaches.

Until these two things change, most supplement studies are doomed to failure. They are doomed to give negative results. In addition, meta-analyses based on these faulty supplement studies will fall victim to what computer programmers refer to as “Garbage In, Garbage Out”. If the data going into the analysis is faulty, the data coming out of the study will be equally faulty. It won’t be worth the paper it is written on. If you are looking for personal guidance on supplementation, this study falls into that category.

 

Should We Use Supplements For Cardiovascular Health?

 

If you want to know whether supplements decrease heart disease risk for everyone, this meta-analysis is clear. Folic acid may decrease the risk of stroke and heart disease. A B complex supplement may decrease the risk of stroke. All the other supplements they included in their analysis did not decrease heart disease risk, but the analysis did not include vitamin E and/or omega-3s.

However, if you want to know whether supplements decrease heart disease risk for you, this study provides no guidance. It did not ask the right questions.

I would be remiss, however, if I failed to point out that we know healthy diets can decrease heart disease risk. In the words of the authors: “The recent science-based report of the U.S. Dietary Guidelines Advisory Committee, also concerned with [heart disease] risk reduction, recommended 3 dietary patterns: 1) a healthy American diet low in saturated fat, trans fat, and meat, but high in fruits and vegetables; 2) a Mediterranean diet; and 3) a vegetarian diet. These diets, with their accompanying recommendations, continue the move towards more plant-based diets…” I cover the effect of diet on heart disease risk in detail in my book, “Slaying The Food Myths”.

 

The Bottom Line

 

You have probably seen the recent headlines proclaiming: “Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.” The study behind the headlines was a meta-analysis of 127 randomized control trials looking at the effect of supplementation on heart disease risk and mortality.

  • The headlines qualify as “fake news” because:
    • The study found that folic acid decreased stroke and heart disease risk, and B vitamins decreased stroke risk. Somehow the headlines forgot to mention that.
    • The study found that multivitamins, vitamin D, calcium, and vitamin C had no effect on heart disease risk. These are nutrients that were unlikely to decrease heart disease risk to begin with.
    • The study did not include vitamin E and omega-3s. These are nutrients that are likely to decrease heart disease risk when the studies are done properly.
  • The authors of the study stated that a major weakness of their study was that that randomized control studies included in their analysis were short term, whereas longer duration studies might be required to fully capture chronic disease risk.
  • The study behind the headlines is of little use for you as an individual because it asked the wrong question.
  • Most clinical studies focus on the “Does everyone benefit from supplementation question?” That is the wrong question. Instead we need more clinical studies focused on the “Who benefits from supplementation?” question. I discuss that question in more detail in the article above.
  • In addition, most clinical studies of supplementation are based on the drug model. They are studying supplementation with a single vitamin or mineral, as if it were a drug. That’s unfortunate, because vitamins and minerals work together synergistically. What we need are more studies of holistic supplementation approaches.
  • Until these two things change, most supplement studies are doomed to failure. They are doomed to give negative results. In addition, meta-analyses based on these faulty supplement studies will fall victim to what computer programmers refer to as “Garbage In, Garbage Out”. If the data going into the analysis is faulty, the data coming out of the study will be equally faulty. It won’t be worth the paper it is written on. If you are looking for personal guidance on supplementation, this study falls into that category.
  • If you want to know whether supplements decrease heart disease risk for everyone, this study is clear. Folic acid may decrease the risk of stroke and heart disease. A B-complex supplement may decrease the risk of stroke. All the other supplements they included in their analysis did not decrease heart disease risk, but they did not include vitamin E and/or omega-3s in their analysis.
  • If you want to know whether supplements decrease heart disease risk for you, this study provides no guidance. It did not ask the right questions.
  • However, we do know that healthy, plant-based diets can decrease heart disease risk. I cover heart healthy diets in detail in my book, “Slaying The Food Myths.”

 

For more details, read the article above.

 

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

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