Omega 3 Fatty Acids: Evidence, Testing and Practical Use

Omega 3 supplements are among the most widely taken supplements in the world, largely on the promise of protecting the heart and brain. The story of the research behind them is a useful case study in how nutrition evidence evolves: promising observations, a series of large trials that mostly disappointed, one striking positive result, a debate about its interpretation, and a picture that is now clearer but more modest than the marketing suggests.

The family of omega 3 fats

Alpha linolenic acid, ALA, is found in flaxseed, chia, walnuts, hemp, rapeseed oil and soy. It is an essential fatty acid, meaning it must come from the diet.

Eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA, are the long chain forms found mainly in oily fish such as salmon, mackerel, sardines, herring and anchovies, and in marine algae, which is where fish obtain them. DHA is a major structural component of the brain and retina.

The body can convert ALA to EPA and, to a lesser extent, DHA, but conversion is limited and variable, generally higher in women than men. People who eat no fish rely on this conversion or on algal supplements.

Omega 3 fats are incorporated into cell membranes and are precursors of signalling molecules, including specialised mediators involved in resolving inflammation. They influence triglyceride metabolism, heart rhythm, platelet function and inflammatory responses.

The evidence by outcome

Triglycerides: well established

EPA and DHA at doses of around 2 to 4 grams a day lower triglycerides substantially, often by a quarter or more in people with high levels. Prescription omega 3 products are used for severe hypertriglyceridaemia, particularly to reduce the risk of pancreatitis.

Cardiovascular events: mixed

Observational studies consistently found that people who eat fish regularly have lower cardiovascular risk. Trials of supplements have been less consistent.

The contrast between REDUCE IT and STRENGTH has been much debated. One explanation is that high dose purified EPA has effects that combined EPA and DHA do not. Another concerns the placebos: REDUCE IT used mineral oil, which raised LDL cholesterol and inflammatory markers in the control group, possibly exaggerating the apparent benefit, whereas STRENGTH used corn oil. The debate is unresolved. What is clear is that the benefit seen with high dose purified EPA in a specific high risk population cannot be extrapolated to standard fish oil capsules in the general population.

Atrial fibrillation: a risk

A meta analysis of cardiovascular outcome trials found that omega 3 supplementation was associated with a modestly increased risk of atrial fibrillation, particularly at doses above 1 gram a day. This is relevant when considering high dose supplementation.

Pregnancy

A Cochrane review found that omega 3 supplementation during pregnancy, mainly DHA, reduced the risk of preterm birth and early preterm birth, and possibly low birth weight. Adequate DHA intake is recommended in pregnancy, from fish low in mercury or from supplements.

Mood and cognition

Some trials suggest a modest benefit of EPA predominant supplements as an adjunct in depression, but results are inconsistent. Trials in the general population have not shown prevention of cognitive decline.

Joint and inflammatory conditions

Omega 3 supplements have shown modest reductions in joint pain and stiffness in rheumatoid arthritis in some trials, sometimes allowing reduced use of anti inflammatory drugs.

Dry eye disease

A large trial found that omega 3 supplements were no better than placebo for dry eye disease, contradicting earlier smaller studies.

Testing

The omega 3 index, the proportion of EPA and DHA in red blood cell membranes, is used in research and offered by some laboratories. Lower values are associated with higher cardiovascular risk in observational studies. It can show whether a person’s intake is low and whether supplements are being absorbed, but targets based on it have not been validated in trials, and it is not part of routine clinical guidelines.

Food first

For most people, the most evidence based approach is to eat oily fish once or twice a week, a recommendation made by many heart and dietary guidelines. This provides EPA and DHA along with protein, vitamin D, iodine and selenium, and replaces less healthy foods. Choosing smaller oily fish, such as sardines, mackerel and anchovies, reduces mercury exposure. People who eat no fish can use plant ALA sources and consider algal oil supplements, particularly in pregnancy.

Using supplements well

• Clear indications: severely raised triglycerides, under medical supervision; pregnancy and breastfeeding in people with low fish intake; people who do not eat fish and want a source of long chain omega 3.
• Dose matters: standard capsules contain varying amounts of EPA and DHA; check the label for the actual content rather than the total oil.
• Quality: omega 3 oils oxidise; products should be fresh and stored appropriately.
• Bleeding risk: at usual doses the effect on bleeding is small, but caution is reasonable with anticoagulants at high doses and before surgery.
• Atrial fibrillation: the increased risk at higher doses should be considered, particularly in people with other risk factors.
• Cod liver oil also contains vitamin A, which limits its safe dose, particularly in pregnancy.

An illustrative case

A 60 year old man with type 2 diabetes, on a statin, with triglycerides of 3.8 millimoles per litre, takes one standard fish oil capsule a day believing it protects his heart. His diet includes little fish and many refined carbohydrates, and he drinks alcohol most evenings.

His plan starts with the changes most likely to lower his triglycerides: reducing refined carbohydrate and alcohol, eating oily fish twice a week and improving glucose control with his physician. His physician then reviews his cardiovascular risk and considers whether a prescription omega 3 product is indicated, in line with local guidelines. The single capsule, providing a low dose, is unlikely to be doing much either way. His triglycerides fall substantially with dietary change and better glucose control alone.

A clearer picture

Omega 3 fatty acids matter: they are essential nutrients, fish consumption is associated with better health, and specific high dose uses have evidence. But the idea that a daily fish oil capsule protects the heart of an average adult has not been supported by the largest trials. Practitioners serve patients best by recommending fish in the diet, reserving supplements for clear indications, and explaining the evidence honestly.