Fish Oil

Fish Oil 101: Demystifying Omega-3 Fatty Acids

Written by Dr. Laura Jones

The words “fish oil” lead people to visualize a less than pleasant childhood memory of their mother pushing a tablespoon of cod liver oil into their mouth, insisting that it would keep them healthy.

As usual, our mothers were right! I know, it sounds too slimy and smelly to be good for you. However, fish oil has more to offer than most people realize. Fish oil is rich in omega-3 fatty acids which are essential fatty acids (EFAs) that our bodies are unable to create on their own. Since we cannot create them, we must obtain EFAs from nutritional sources. Most people do not get enough of these polyunsaturated fats from their food, even those of us who prioritize fish in our nutrition plans. Therefore, supplementation with fish oil can be quite valuable. EPA and DHA are two omega-3 fatty acids particularly beneficial to our health. Both play critical roles in cognition and learning, immune system function, combating inflammation, brain development in children and in pregnancy. Both fatty acids are the subject of 1000s of studies, identifying their roles in the prevention of dementia, heart disease, high blood pressure, arthritis, cancer, mental illness and so much more. They affect every one of the hundred trillion cell membranes in your body.

A large amount of research on omega-3s has focused on their effects on heart disease. EPA and DHA consumption are linked to lower triglyceride levels, decreasing one’s risk for atherosclerosis. A more recent meta-analysis, published in The Lancet (July 2021), looked at 38 randomized controlled trials involving 150,000 patients and summarized that omega-3 fatty acids reduced cardiovascular mortality and improved cardiovascular outcomes. These two fatty acids can also decrease inflammation in the body, improve how well our immune system keeps us healthy, and promote skin, hair, and nail health.

Recent clinical research has shown that not only the quantity of fat in the diet, but also the type of fat affects body weight and metabolism. Diets rich in omega-3 oils result in healthier body weight and metabolism as well as the best body composition in terms of fat/muscle ratio. In addition, fish oils function as strong antioxidants throughout the body and improve the oxygen delivery to cells thus improving aerobic performance. If purchasing fish oil, make sure it is from a reliable source, free of environmental contaminants (pesticides and heavy metals), and contains vitamin E to protect and preserve the oil. It is important to store your oil in a cool location, away from direct light. It is critical to make sure the company producing the supplement is committed to clean sourcing of the fish oil as any contaminants in the fish will end up in those consuming the oil.

Excellent quality fish oils come in various formulations with different ratios of DHA and EPA. While both oils are very important for idea health, DHA has greater affinity for the brain and nervous system while EPA plays more of a role in reducing inflammation in the body. A formulation higher in DHA may be better suited for mood support in a person struggling with anxiety or depression, or a student challenged with difficulty focusing on their schoolwork. Formulas higher in EPA tend to be better for inflammatory conditions such as autoimmune disease, arthritis, or for an athlete in active training and recovery.

Some ask, what about if I eat fish a couple times a week? Should I still consider a supplement? The answer is yes. Therapeutic doses of omega-3 fatty acids start at around 1000mg per day but can go up as high as 6000-8000mg per day in divided doses. For many of my patients, I am recommending 1000-2000mg twice daily. Referencing the chart below, you can see that even with a sizable amount of salmon weekly, it would be hard to eat sufficient amounts of EPA and DHA. It is also important to consider the toxic load of the fish. Wild Alaskan salmon or Sockeye salmon is a much cleaner fish to frequently work into your nutrition plan than a fish like halibut, haddock, or swordfish. Smaller fish such as anchovies, sardines and mackerel are small and do not live long enough to accumulate toxins. You’ll notice I didn’t include tuna on this list, as it tends to be a very toxin laden fish due to its size, and I’d rather my patients eat it on rare occasion for this reason.

Amount of Omega-3 (grams) per 3.5oz. serving of fish

Mackerel 2.6 Salmon 1.5 Sardines, canned 1.5 Anchovies 1.4 Bass, striped 0.8 Trout, rainbow 0.6 Halibut, Pacific 0.5 Flounder 0.2 Haddock 0.2 Snapper, red 0.2 Swordfish 0.2

At times, we hear people report that fish oil has been difficult to take because it upsets their digestion, or it causes reflux or eructation. In most of these cases, the person is either taking a poor-quality omega-3 supplement or has poor digestion that needs to be corrected prior to taking a higher potency omega-3. Whole Health Concord’s Wellness Shop has many different omega-3 supplements for adults and children. You are welcome to come peruse our shelves and ask us for help if you are not on a superior quality supplement already.

Habitual Use of Fish Oil Prevents CVD, Real-world Data Suggest

The findings are, in fact, complementary to recent trials showing no overall benefits of supplementation, JoAnn Manson argues.

Routinely taking fish oil supplements rich in omega-3 fatty acids may help prevent cardiovascular disease and related mortality over the long term in people initially free of heart disease, new observational data suggest, adding to the ongoing debate about the role of fish oil supplements for primary prevention.

In the UK Biobank cohort, self-reported habitual use of fish oil supplements at baseline was associated with lower risks of incident CVD events and of all-cause and CVD mortality over a median follow-up of 8 to 9 years (adjusted HRs ranging from 0.84 to 0.93), according to researchers led by Zhi-Hao Li, PhD (Southern Medical University, Guangzhou, China).

“These findings indicate that habitual use of fish oils is associated with a marginal benefit for CVD events in the general population, supporting their use for the prevention of mortality from all causes and CVD,” Li et al write in their paper published online March 4, 2020, ahead of print in the BMJ. “Future studies are needed to examine the extent to which the dose of fish oil supplements influences the ability to achieve a clinically meaningful effect.”

The results appear at first glance to conflict with those of the VITAL trial, which failed to show that fish oil reduced major cardiovascular events or new cancer diagnoses in men and women free from cancer and CVD at baseline. There was a reduction in the secondary endpoint of MI, however, and exploratory analyses suggested lower risks of total coronary heart disease (CHD) and PCI.

Dariush Mozaffarian, MD, DrPH (Tufts Medical School, Boston, MA), said those secondary and exploratory endpoints in what was a null trial are important because decades of study has suggested that fish oil supplementation would reduce risk of CHD and not total CVD. “If that was a random finding, I would be less focused on it, but that’s exactly what we would have predicted based on the mechanistic studies,” he commented to TCTMD.

Based on VITAL, “if I were making guidelines, I would say that there is some evidence that fish oil could reduce coronary heart disease in primary prevention,” Mozaffarian said. “It’s not cut and dried. It’s not absolute. We need at least probably two more large definitive trials to make it cut and dried and absolute, but it’s certainly suggestive. And when you combine it with no evidence for harm and other studies like this one, observational studies, I think the overall body of evidence is supportive.”

Evidence Is Mixed

Although fish oil supplements have become popular based on observational studies supporting a benefit in terms of CVD risk reduction, some recent randomized trials have dampened enthusiasm. In addition to VITAL, ASCEND showed that omega-3 fatty acid supplementation failed to reduce serious vascular events in diabetic patients without established cardiovascular disease.

Recent meta-analyses of randomized trials have provided conflicting results. One published in 2018 before results from ASCEND, VITAL, and REDUCE-IT were released showed that omega-3 fatty acid supplementation was not associated with reduced risks of CHD, stroke, coronary revascularization, and any major vascular events in high-risk patients. A more recent meta-analysis published in 2019 that included those trials, in contrast, demonstrated that supplement use was tied to lower risks of MI, total CHD, death from CHD or CVD, and total CVD, even when REDUCE-IT—which showed significant benefits of a prescription omega-3 fatty acid formulation in patients with high triglycerides—was excluded.

We need at least probably two more large definitive trials to make it cut and dried and absolute, but it’s certainly suggestive. Dariush Mozaffarian

“Although randomized controlled trials generate the best evidence for the effects of interventions, their findings are difficult to generalize to large, more-inclusive populations because of their well-known limitations,” Li et al write. “Therefore, complementary information on the effectiveness of fish oil supplements is needed through evaluation in real-life settings of large-scale cohort studies.”

UK Biobank

To that end, they examined data from the UK Biobank, a population-based cohort of more than half a million people ages 40 to 69 from England, Scotland, and Wales. The current analysis included 427,678 people (mean age 56 years; 55% women) who did not have CVD or cancer at baseline and who had information on supplement use available. At baseline, 31.2% said they regularly took fish oil supplements. Patients were then followed for a median of 8.1 years for CVD events and 9.0 years for mortality.

On multivariable adjustment, habitual use of fish oil supplements was associated with lower risks of a variety of CVD-related outcomes, except for fatal stroke.

Long-term Outcomes Before and After Multivariable Adjustment

Regular Fish Oil Users Nonusers Adjusted HR (95% CI) All-Cause Mortality 3.1% 3.0% 0.87 (0.83-0.90) CVD Mortality 0.8% 0.8% 0.84 (0.78-0.91) Incident CVD 4.4% 4.2% 0.93 (0.90-0.96) MI Mortality 0.3% 0.3% 0.80 (0.70-0.91) MI 1.8% 1.8% 0.92 (0.88-0.96) Stroke Mortality 0.2% 0.2% 0.87 (0.73-1.04) Stroke 1.0% 0.9% 0.90 (0.84-0.97)

The relationship between use of fish oil and CVD event risk appeared stronger in patients with prevalent hypertension, whereas the associations with all-cause mortality risk seemed stronger for men and current smokers.

Discrepancy Between Studies

The investigators say that other studies that have not shown significant relationships between fish oil supplementation and CVD prevention could have suffered from insufficient sample sizes and numbers of outcome events.

In VITAL, for instance, they calculated the post hoc study power for major cardiovascular events to be only 0.78. They note, too, that the point estimate for a reduction in CVD events was similar in VITAL (HR 0.92) and this study (HR 0.93). “The confidence interval estimation (0.90 to 0.96) in our study suggests that omega-3 fatty acids have a significant association with CVD events,” Li et al write. “Therefore, we postulate a marginal inverse association between fish oil supplementation and CVD events.”

The researchers also say that dose may come into play, noting that the dose of omega-3 fatty acids was about 4.75-fold higher in REDUCE-IT, which met its primary endpoint, than in VITAL. Moreover, the 2019 meta-analysis indicating a benefit of fish oil also showed that higher doses would be more effective. “This finding indicates that the conflicting results from the randomized controlled trials could be due to sample sizes and the doses of fish oil supplements,” Li et al say.

They acknowledge that their own analysis has some limitations, including the lack of detailed information on dose, formulation, and duration of fish oil use; the potential for confounding or reverse causality; and the difficulty in separating the effects of a healthy lifestyle from those of fish oil supplementation.

Taking Fish Oil ‘Very Reasonable’

Commenting for TCTMD, JoAnn Manson, MD, DrPH (Brigham and Women’s Hospital and Harvard Medical School, Boston, MA), one of the chairs of the VITAL steering committee, said that “observational studies of supplement users and health outcomes need to be considered with caution because there are many potential confounding factors that come into play in terms of who chooses to take supplements and who chooses not to.” Thus, correlations in observational data do not prove causation.

That said, real-world data can be complementary to information from randomized clinical trials, especially when the two are reasonably well aligned, as is the case with studies looking at the impact of omega-3 fatty acid supplementation on coronary risk, Manson added.

“I think we have a good idea now of the effect of omega-3s on heart health,” she said. “There does seem to be a benefit for reducing risk of coronary disease.”

There is a need for additional studies, however, and both randomized and observational studies have a role to play, Manson said. In particular, additional trials looking at omega-3 fatty acid supplementation for primary prevention in high-risk patients are needed, with varying doses and formulations. But trials can be limited in their ability to look at long-term use, she added, highlighting the need for more observational research as well.

Mozaffarian also underscored the importance of observational research—with all of its inherent limitations—when examining the impact of interventions like fish oil supplementation on long-term disease risks.

“Trials and observational studies each have their own strengths and limitations, and of course animal experiments and other types of mechanistic studies have their own strengths and limitations,” he said. “I think there’s been an overreliance and an overemphasis on randomized controlled trials as the only standard and really we have to use all the evidence. So I think if you put all the evidence together—the evidence from VITAL, the evidence from REDUCE-IT, the evidence from ASCEND, the evidence from this study—it supports . . . that low-dose fish oil supplements probably have some cardiovascular benefit.”

If people want to improve their health, and indications are that eating omega-3 fatty acids is important, Mozaffarian said, “then my number one recommendation is still to do so by eating oily fish two or three times per week. But if people can’t eat oily fish two or three times per week for whatever reason . . . or if they do eat oily fish but still want to be sure they’re getting enough omega-3s, taking a daily nonprescription fish oil supplement is very reasonable.”

Ask-the-Expert: The beneficial role of omega-3 fatty acids across the lifespan

Why and when do we need EPA and DHA omega-3s?

As Dr. Van Dael explains, omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) are among the most highly studied nutrients and have important roles in many processes in the human body throughout the lifecycle.

Beyond heart, brain and eye health, EPA and DHA address a myriad of trending concerns. In recent years, scientific literature describes a wide variety of other areas of health where clinically-supported benefits of omega-3s are emerging, including immunity, sleep, sports performance and mood.2,3,4,5,6,7 But, while these benefits are supported by a growing body of scientific evidence, they are not necessarily top-of-mind for existing omega-3 consumers or individuals seeking solutions to support holistic health and wellness.

In addition to the examples discussed by Dr. Van Dael, it is now known that EPA and DHA omega-3s and their metabolites have an important role in resolving inflammation, which supports normal immune function. EPA and DHA molecules present at the site of inflammation are enzymatically converted to pro-resolving mediators (SPMs) known as resolvins, protectins, and maresins. These molecules, along with others, function together to coordinate the resolution of inflammation and to support healing.2

Furthermore, omega-3s, particularly DHA, may help to make a good night’s rest a reality for all age groups, with regular fish consumption shown to improve length and quality of sleep.8,9,10 Interestingly, low tissue levels of DHA are associated with lower levels of the hormone melatonin, which helps individuals fall asleep.11 DHA is also well-known to have a positive long-term effect on neurocognitive development.12 Both EPA and DHA omega-3s have more recently shown positive effects on the reduction of symptoms associated with mood disorders. Indeed, increasing evidence suggests that lower levels of omega-3 in the plasma may be linked to poorer mental health, including conditions related to mood.3,6

What is the case for people to take omega-3s supplements?

In the interview, Dr. Van Dael explains why current dietary habits mean that less than 20% of the world’s population1 achieve the minimum intake of EPA and DHA set by most expert bodies at 250-500 mg per day.13

A regular, healthy intake of omega-3s can be readily achieved by supplementation with micro-algal oils. For the increasing number of people making more sustainable choices and adopting plant-based lifestyles, micro-algal oil is an attractive alternative to omega-3s derived from fish oil. Micro-algal oil production is fully sustainable and environmentally friendly, enabling dietary supplement manufacturers to create solutions that appeal to a new generation of omega-3 consumers and align with preferences for products that support both their health and the health of the planet.

What services can DSM offer omega-3 supplement manufacturers with regard to successful product development?

DSM not only produces its omega-3 products to the highest quality requirements, but also offers expert services, including scientific and regulatory support, to its customers.

Understanding the needs, challenges and trends that can inspire the creation of innovative and appealing solutions is essential for today’s dietary supplement manufacturers. As an end-to-end partner, DSM brings consumer insights, scientific expertise and market-ready solutions and takes a consumer-centric approach, contributing insights and innovation into every stage of the product development lifecycle.

DSM’s broad range of high-quality EPA and DHA omega-3 products includes its enhanced life’s™OMEGA portfolio – the only plant-based, sustainably-produced omega-3 fatty acid that combines EPA and DHA in a single, quality source. Made from fermented non-GMO micro-algae, life’s™OMEGA is around 85% more potent than omega-3 derived from fish oils.

Discover innovation opportunities to develop omega-3 products with purpose and attract a new generation of consumers - visit the life’s™OMEGA content hub.

Eric Carter