Are Many Fish Oils Synthetic?

fish oil supplement

Story at-a-glance -

  • The health benefits of DHA and EPA are well-established. Despite that, a number of studies have found no benefit when studying the effects of fish oil supplements, which are generally accepted as a convenient source of these important fats
  • Many nutritional studies fail to assess the correct parameters. The importance of looking at achieved blood levels of a nutrient rather than dosage has been clearly demonstrated by vitamin D researchers
  • Processing of fish oil is deeply problematic, rendering the final product into something far from the natural oils you get from the whole fish
  • In fish, the DHA and EPA are in the form of triglycerides, which are the most bioavailable. In most fish oil supplements, the DHA and EPA are delivered in the form of ethyl esters — a synthetic substrate with low bioavailability
  • Ethyl ester fish oils are not as effective for raising your omega-3 index. Your liver must also process the ethyl alcohol, which may release free radicals and cause oxidative stress — the complete opposite of what you’re trying to achieve by taking a fish oil supplement

By Dr. Mercola

Omega-3 fats are essential polyunsaturated fats (PUFA) required for healthy digestion, muscle activity, blood clotting, visual acuity, memory and much more. Most omega-3s are considered "essential fats" as your body cannot make them. You have to get them from your diet. However, there's plenty of confusion when it comes to which omega-3 fats are required for optimal health.

You can obtain omega-3 fats from both plants and marine animals like fish and krill. However, these sources provide very different types of omega-3, and they are no way interchangeable.

Both plant- and animal-based omega-3 have their first double-bond in the third position — hence the name "omega-3." However, the length of the carbon chain of each omega-3 fat makes a significant difference when it comes to bioavailability and biological effect.

Basic Differences Between Plant- and Marine Animal-Based Omega-3s

Animal-based omega-3 — found in fatty fish, fish oil and krill oil — primarily contain docosahexaenoic acid (DHA), a long-chained PUFA consisting of 22 carbons, and eicosapentaenoic acid (EPA), which has 20 carbons.

Plant-based omega-3 — found in flaxseed, flaxseed oil, chia seeds, walnuts and leafy greens, for example — contain alpha-linolenic acid (ALA), a shorter-chained PUFA consisting of 18 carbons. Plant-based omega-3 is completely devoid of DHA and EPA.

ALA is indeed a precursor to EPA and DHA, which is why some say you can simply consume plant-based omega-3s. However, an enzyme is required to convert the shorter 18 carbon ALA into long-chained omega-3, and in most people, this enzyme is simply unable to convert sufficient ALA to EPA, and even less DHA.

Typically, less than 1 percent of the ALA is converted to EPA. Some studies have found the conversion rate to be as low as 0.1 to 0.5 percent.1 So, while a tiny amount of the ALA you consume can be converted by your body into long-chain omega-3, it's a highly inefficient strategy and nowhere near as helpful as supplying "straight" DHA and EPA from marine sources.

Importantly, short-chain fatty acids are used by your body as a source of energy, while the long-chain fatty acids, those with 20 and more carbons, especially EPA and DHA, are structural elements that actually make up your cells. This is perhaps the most significant difference between plant- and animal-based sources, and why they are not interchangeable from a health perspective.

As structural elements, DHA and EPA are particularly important for proper cell division and function of cell receptors. They also play an important role in anti-inflammatory reactions. These fats are ideally obtained from the consumption of small fatty fish that are free of toxins. Unfortunately, most people opt for fish oil supplements over eating fatty fish like sardines, anchovies and herring.

Research Finds No Support for Fish Oil Supplementation on Heart Health

Overall, the health benefits of DHA and EPA are well-established.2 Research has provided clear evidence that higher intake of these animal-based omega-3 fats reduces your risk of heart disease and other chronic diseases, and are vital for neurological health.

Despite that, a number of studies have come up with conflicting results when studying the effects of fish oil supplements, which are generally accepted as a convenient source of these important fats. Here, I'll review some of the reasons for these odd discrepancies.

Most recently, a Cochrane Collaboration review3 of available evidence concluded omega-3 supplementation has little to no discernible benefit for heart health or longevity. As reported by the Cochrane Library:4

"A new Cochrane systematic review … combines the results of 79 randomized trials involving 112,059 people. These studies assessed effects of consuming additional omega-3 fat … on diseases of the heart and circulation … Participants were randomly assigned to increase their omega-3 fats or to maintain their usual intake of fat for at least a year.

Most studies investigated the impact of giving a long-chain omega-3 supplement in a capsule form and compared it to a dummy pill … The Cochrane researchers found that increasing long-chain omega-3 provides little if any benefit on most outcomes that they looked at.

They found high certainty evidence that long-chain omega-3 fats had little or no meaningful effect on the risk of death from any cause. The risk of death from any cause was 8.8 percent in people who had increased their intake of omega 3 fats, compared with 9 percent in people in the control groups.

They also found that taking more long-chain omega 3 fats (including EPA and DHA), primarily through supplements probably makes little or no difference to risk of cardiovascular events, coronary heart deaths, coronary heart disease events, stroke or heart irregularities."

Why Studies Don't Always Support Health Effects of Nutritional Supplementation

There are a number of reasons for these kinds of complexing results. First of all, many nutritional studies fail to assess the correct parameters. The importance of looking at achieved blood levels of a nutrient rather than dosage has been made abundantly clear by GrassrootsHealth vitamin D researchers.

When studies look at dosage, no apparent benefits of vitamin D supplementation are found. However, when you look at people's blood level — the concentration of the nutrient in the body — truly dramatic effects are detected.

The problem is that people metabolize the nutrient at different rates, and while one may need a very small dose to achieve a certain blood level, another may need several times that dose. So, assessing health effects based on supplement dosage can be extremely unreliable.

Scientific American5 also weighed in on the issue, noting that "… a quartet of new studies … may give insight into why human clinical trials of fish oil have failed to protect against AD [Alzheimer's disease] and other forms of dementia."

The Role of Your Microbiome and Liver in Omega-3 Metabolism

In these four studies, blood levels of molecules associated with lipid (fat) production in the liver were found to be linked to AD risk. Your brain, being made mostly of fats, need fats for optimal functioning as the lipids are involved in neuronal communication and nerve cell insulation.

Your liver is responsible for producing many of these important fats, and genes linked to AD are also involved in fat production and transport. APOE ε4, which is associated with a high risk for AD, is one of them. Your gut microbiome also plays a role in the processing of omega-3 fats, as do bile acids, produced from cholesterol in your liver.

When you consume omega-3 fats, certain microbes in your gut participate in the metabolism of these lipids. Your liver takes over during the final phase, creating brain-specific fats called peroxisomes, which are then transported via your blood stream into your brain. As reported by Scientific American:6

"Recognizing the central role of the liver in the brain's health, the four research groups measured blood levels of these brain-critical lipids and the molecules that make them … One group … looked at lipids called plasmalogens, fats that contain the omega-3 fatty acids DHA and EPA.

They found reduced blood levels of these fats tracked with increased AD risk … A second group … found similar hints of lipid-processing anomalies in blood samples.

In the latter study, even people with AD who took fish oil supplements did not have increased blood levels of brain-beneficial lipids, possibly pointing to why fish oil supplementation does not appear to stem cognitive decline.

If peroxisomes in the liver are not working properly, 'taking more fish oil won't let you make more plasmalogens because the machinery for making them is defective,' says Mitchel Kling, associate professor of psychiatry at the University of Pennsylvania Perelman School of Medicine …"

According to Howard Fillit,7 founding executive director and chief science officer at the Alzheimer's Drug Discovery Foundation, other recent evidence suggests people with the APOE ε4 gene may actually have altered DHA metabolism. Whether this might make them less likely to reap significant benefit from fish oil supplements is unknown, however.

Genetic variations were also linked to bile acid levels in two of the four studies, suggesting AD risk genes may interact with the gut microbiome, and that this is (at least in part) why these genetic variants raise your risk for dementia.

The Problem With Most Fish Oils

As it pertains to fish oil specifically, it's now also becoming clear that the processing of fish oil is deeply problematic, rendering the final product into something far from the natural oils you get from the whole fish. This too appears to be a significant piece of the puzzle that helps explain why fish oil supplementation appears to be ineffective in some studies. As described by former CEO of Twinlab, Naomi Whittel:

"Even if you think the fish oil is coming from Norway or Europe, [the fish] is caught in Central and South America … The fish are then brought onto and thrown into the bottom of the boat …

By the time they get to Europe, the guts are so rancid that in order to get the omega-3s out, they have to go through a process of extracting these poisons and this rancidity. [In the end], you're left with something that has none of the cofactors [and] it's been heavily contaminated to clean out the rancidity …"

Whittel estimates about 98 percent of the omega-3 products on the market are inferior (and perhaps even toxic) due to the way the fish are caught and processed — a summary of which is provided in the graphic below.

fish oil molecular distillation process

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Triglyceride Versus Ethyl Ester Fish Oils

Several factors come into play that affect the efficacy of fish oil. One is the form of the long-chained omega-3 fats. In fish, about 98 percent of the DHA and EPA are in the form of triglycerides, which are the most bioavailable. In most commercial fish oil supplements, however, the DHA and EPA are delivered in the form of ethyl esters.8

A triglyceride consists of a three-carbon molecule that forms a "backbone" for the fatty acids to latch onto. Each carbon molecule is linked to a fatty acid, so in total, a triglyceride is composed of three carbons bonded to three fatty acids.

Ethyl ester fish oil is most prevalent simply because it's far less expensive to produce than the triglyceride form. Ethyl esters are also easier to work with during processing, as they have a higher boiling point. This becomes important during the molecular distillation phase (see above), during which the oils are heated and purified of harmful environmental pollutants.

The molecular distillation phase also concentrates the EPA and DHA. You can tell the concentration of these two fats in any given supplement by looking at the label. In fish, the oil consists of about 20 to 30 percent EPA and DHA, whereas purified fish oil concentrate typically contains between 60 and 85 percent EPA and DHA.

Ethyl esters are essentially a synthetic substrate, created through the micro distillation process of crude fish oil, in which ethanol and/or industrial alcohol is added. This mix is heat distilled in a vacuum chamber, resulting in a concentrated omega-3 ethyl ester condensate.

It is also important to note that this purifying molecular distillation process removes vital resolvins and protectins present in the raw material that are important in reducing inflammation.

synthetic and natural fish oil

Ethyl Esters Are Poorly Absorbed

Ethyl esters, unfortunately, are the least bioavailable form of omega-3, and while manufacturers could convert them back into triglyceride form (by detaching the ethyl alcohol molecule and reattaching a glycerol molecule in a process known as re-esterification), this process is a costly one.

The difference between triglyceride and ethyl ester forms become an issue when your body goes to metabolize them. Since the glycerol backbone is missing in the ethyl ester form, the EPA and DHA will scavenge for available triglycerides or steal a glycerol molecule from somewhere.

When the latter happens, the molecule that lost its glycerol will now go searching for a replacement, which creates a domino effect. One way or another, the fatty acids need to be converted back into triglyceride form, or else your gut epithelium will not be able to process them.

The fatty acids also cannot be transported through your blood unless they're in triglyceride form. When you consume omega-3s in triglyceride form, the fatty acids are first separated from the glycerol backbone. All of the individual parts are then absorbed by gut epithelial cells, where they're reattached to form triglyceride.

On the other hand, when you consume ethyl esters, they must be processed in your liver. There, the ethanol backbone is separated from the free fatty acids, and your body must then reattach the free fatty acids to glycerol to form triglyceride. As you may imagine, this process is far less efficient, compared to the processing of omega-3 fatty acids that are in triglyceride form from the start.

Ethyl Esters May Do More Harm Than Good

Not only does it delay and likely diminish the release of these beneficial triglycerides into your blood stream, your liver must also process the ethyl alcohol, which may release free radicals and cause oxidative stress — the complete opposite of what you're trying to achieve.

Studies9 suggest a mere 20 percent of the EPA and DHA in ethyl ester form are absorbed by your body. When taken with other dietary fat, absorption increased threefold to 60 percent. Meanwhile, EPA and DHA in their natural triglyceride form were found to have a 69 percent absorption rate from the start, and when taken with additional dietary fat, absorption increased to 90 percent.

As a result, taking a triglyceride fish oil results in a 50 percent greater rise in omega-3 blood plasma levels than ethyl ester fish oil. Another major drawback of ethyl ester fish oils is their rapid oxidation rate. Ethyl ester DHA is far more reactive than triglyceride DHA, oxidizing 33 percent more rapidly, and consuming rancid omega-3 is not going to do your health any good. Quite the contrary.

Common side effects of prescription strength fish oil such as Lovaza — a highly concentrated ethyl ester form of fish oil — are primarily due to the toxicity of ethanol, which is separated out in your liver. This includes unpleasant body odor, vomiting, gastrointestinal dysfunction, pancreatitis, cardiac effects and hypertriglyceridemia.

So, in summary, it's important to realize that the vast majority of clinical evidence showing health benefits of omega-3 relates to actual fish consumption, and as mentioned, virtually all of the omega-3s in fish are in triglyceride form.

Ethyl ester omega-3 does not exist in nature — it's a man-made byproduct of fish oil processing. Hence, to achieve reliable results, you really need to either eat omega-3-rich fish, or make sure the supplement you're taking contains DHA and EPA in their triglyceride form. For a more in-depth understanding of these differences, see the paper, "A Comparison of Synthetic Ethyl Ester Form Fish Oil vs. Natural Triglyceride Form,"10 by Dr. Douglas MacKay, who specializes in naturopathy.

Steps for Fish Oil Ethyl Ester Production From Fish Waste11

fish oil ethyl ester production fish waste

Fish Oil Versus Krill Oil

While unrelated to human health effects, fish oil has another significant drawback, namely its environmental impact. Overfishing has become a great concern, and according to recent research, humans have damaged 87 percent of the world's oceans.12,13

According to this study, marine wildlife have dwindled across the globe, thanks to overfishing, global marine shipping and rampant pollution from several sources. The good news is there's an alternative source of marine-based omega-3 fats that doesn't have this impact, and that's krill.

Compared to fish oil, krill oil also has higher potency, and contains natural phospholipids, which makes it more readily absorbed. Krill oil also contains astaxanthin, a powerful antioxidant, which makes if far less prone to oxidation, is virtually contaminant free, and has a superior metabolic influence.

krill oil vs fish oil

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Krill Oil Is a Far More Sustainable Option

Getting back to sustainability, krill is the largest biomass on earth, and krill harvesting is also one of the most carefully regulated. Strict international precautionary catch limit regulations are reviewed and reassessed regularly to assure continued sustainability.

While krill can be found in all oceans, Antarctic krill is by far the most abundant. The Antarctic krill biomass is under the management of an international organism of 25 countries called the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR).14

This is the only official and reliable international organism involved in the management of sustainable krill fishery and the monitoring of krill stock, and no shortage of krill has ever been forecast by CCAMLR.

CCAMLR is viewed as an outstanding framework that is well organized and has developed robust research programs to help ensure successful conservation measures in the Southern Ocean. They also have the authority to further micromanage, on a season to season basis, to counteract any concerns they may have regarding the strength of the krill population during a particular har­vesting season.

CCAMLR has implemented a precautionary approach to minimize any risks associated with harvesting practices in conditions of uncertainty. They also use an ecosystem approach, meaning they take into account ecological links between different species and natural variability, such as the natural, cyclical rise and fall in reproduction of a species.

They also organize the strategic issuing of man­datory krill harvesting licenses as another control mea­sure to promote sustainability, and are proactively combating illegal fishing of all kinds within the Convention Area, to protect the ecosystem. You can learn more about the safeguards in place to ensure the sustainability of krill in this previous krill article.

Your Best Options for Animal-Based Omega-3

Based on the evidence, it seems clear that to reap maximum health benefits, you really want a majority of your omega-3 to come from your diet. That means eating small fatty fish such as sardines, anchovies, mackerel and herring. Wild-caught Alaskan salmon is another good source.

If you opt for an omega-3 supplement, your choices become more complex. What seems obvious is that many commercial fish oil supplements are not going to give you the benefits you're looking for. A key determining factor here is whether the supplement contains the triglyceride form or ethyl ester form of omega-3.

If you are taking a fish oil supplement, it is vital that you find out if the fish oil is a synthetic ethyl ester. If this information is not on the label, contact the manufacturer and find out. ONLY use fish oil that is in the natural triglyceride formulation. Choosing otherwise could be very problematic for your long-term health.

My preference, when it comes to omega-3 supplements, is krill oil, in part because of its superior absorbability, but also because it's a vastly more sustainable source. Last but not least, don't rely on a set dosage when taking a supplement. Like vitamin D, it's your serum level that counts. Your omega-3 level can easily be measured using an omega-3 index test. You'll want your index to be above 8 percent for optimal health and disease prevention.