Omega-3 Fatty Acids: The Basics for Clinicians and Patients

 

Omega-3 fatty acids have broad general health benefits across areas in medicine. They are anti-inflammatory and have well-established cardiovascular benefits.  In addition, several studies have shown that supplementation with omega-3 fatty acids may improve outcomes in those receiving standard treatment for major depression and bipolar disorder.  Here we offer some guidelines for the use of omega-3 fatty acids.

 

Which omega-3 fatty acids are recommended?

The omega-3 fatty acids most broadly studied for human health are eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA).  They have been generally studied and established for health benefits in the combination of EPA + DHA, in ratios with EPA: DHA greater than 1 (more EPA than DHA).  Although DHA is the main omega-3 fatty acid in the brain, only combinations of EPA+DHA (EPA>DHA) or high EPA doses have demonstrated benefit for psychiatric disorders.

It is widely believed that DHA alone is important for fetal and infant neurocognitive development, and prenatal vitamins and infant formulas now include DHA.  However, research in human pregnancy supports supplementation with a combination of EPA and DHA (see table).  Benefits in neurocognitive development in infants have been observed after either greater consumption during pregnancy in population studies or after supplementation in randomized controlled trials with EPA + DHA.   Therefore, prenatal vitamins and formulas with added small amounts of DHA (usually about 200 mg per day) may be on the right track, but insufficient, as studies support the addition of EPA+DHA in greater daily amounts.

Only a few treatment studies have specifically looked at omega-3 fatty acids (EPA + DHA) as a treatment for perinatal depression (doses of 2-3 g per day, EPA+DHA) (Su et al., 2008; Rees et al., 2008; Freeman et al, 2008).

What about flax seed oil and plant sources?

Plant sources contain alpha-linolenic acid, an omega-3 fatty acid that requires extensive metabolism to form EPA and DHA, and appears to be less available for human benefits requiring omega-3 fatty acids.  There have not been any studies at all to suggest a mental health benefit of alpha-linolenic acid, and the overwhelming majority of studies across other fields of medicine have used EPA and DHA.  Therefore, flaxseed oil may be better than nothing, but that isn’t clear at this time.  The benefits of omega-3 fatty acids established to date are with EPA + DHA.

 

What dose?  What ratios of EPA and DHA?  What about fish intake?

Studies in mood disorders and in other fields of medicine (i.e., cardiovascular literature) have used a wide range of doses, anywhere from 1-10 g per day.  The American Heart Association recommends that adults eat fish at least twice weekly, and those with coronary artery disease supplement with 1 g per day of EPA + DHA (4 g per day for high triglycerides).  Most studies across fields of medicine have used combinations of EPA + DHA.

The literature in psychiatry supports a dose of 1-3 g per day as an adjunctive treatment for mood disorders.  While other conditions, particularly high triglycerides may require a higher dose (i.e., 4 g per day) of omega-3 fatty acids, higher dosages may reduce adherence with unclear added benefits.  Positive studies in mood disorders have generally used EPA+ DHA in combination  with some positive results using high ratios of EPA to DHA formulations .  To date, there appears to be a limited role for DHA alone.

Supplementation studies in pregnancy which demonstrated improved neurocognitive development in babies used doses in the range of 2-3 g per day.  Very high ratios of EPA:DHA have not been tested in pregnancy.  More standard ratios of EPA:DHA appear to be safe in pregnancy, with some studies actually showing benefit of pregnancy outcomes.  Studies assessing the impact of omega-3 fatty acids on risk of preterm delivery have been inconsistent, but omega-3 fatty acids may modestly increase length of gestation.

EPA: DHA in ratios found in standard products are ideal for pregnancy (between 1:1 or 3:2, similar amounts of EPA and DHA, although most brands will have a bit more EPA than DHA).  The higher dose EPA to DHA ratios (often labeled as pure EPA, in ratios such as 5:1 or 7:1) may have the most evidence for indications such as depression and hot flashes.  These may be fine – and actually preferable – for the non-pregnant patient.  These formulations are not yet established as safe in pregnancy.

Are pregnant women supposed to avoid eating fish?

Yes, but mostly no.  The requirement for omega-3 fatty acids is higher in pregnancy than other times due to the developing baby’s requirements for optimal brain development, and intake of omega-3 fatty acids by pregnant and lactating women in the U.S. has been historically inadequate, reaching only 20-60% of intake recommended (Benisek et al., 2000).  The U.S. FDA mercury advisories precipitated further decline in intake among pregnant women, and a fair amount of confusion.

To avoid mercury exposure, the four species the FDA recommends avoiding are 1) tilefish, 2) shark, 3) swordfish, and 4) king mackerel.

Other fish intake by pregnant women should be limited to 12 ounces per week.  Many women interpret the guidelines as stating that women should avoid fish consumption during pregnancy.  And indeed many do.  Omega-3 fatty acid dietary intake has decreased during pregnancy since the advisory, in parallel with mounting evidence that omega-3 fatty acid intake is required for optimal neurocognitive outcomes in infants (Oken et al, 2003 & 2005; Helland et al., 2003).

How do I figure out how much omega-3 fatty acids are in the capsules?

Look at the front of the bottle.  Most state “1000 mg” on the front.  Completely disregard this—it pertains to the weight of the capsule and not the EPA and DHA that are critical.

Turn the bottle around to the food label and look at the fine print on the back or side.  Check how many capsules are in a serving.  Then add up the total EPA and DHA to equal the dose per serving.

What about the purity of a given preparation? What about contaminants?

Consistently, major brand fish oil capsules/supplements have been demonstrated to not contain mercury (Foran 2003).  They are made in a way that removes contaminants such as mercury, and testing has confirmed this.  Good quality supplements should have evidence of purity testing on the labels of their products or websites, and extensive testing data should be available on request.  Buyer beware, as always, but there are some voluntary standards for food supplements to which some companies adhere, and purity data is available for good brands.  Check websites or contact the manufacturer directly when in doubt.

Brands may differ in encapsulation quality and freshness.  If capsules are really yucky with a lot of fishy aftertaste, throw out the bottle and start over with the above recommendations in mind.

How do I explain the potential benefits to my patient without overselling?

Cardiovascular benefits for adults and benefits for babies are well established.  Omega-3 fatty acids are important for optimal human health and fetal/infant development.  Omega-3 fatty acids may have an antidepressant effect, but the role most established to date is as an add-on treatment to antidepressants.

Marlene Freeman, MD