Omega-3 fatty acids: Facts and controversies

Omega-3 fatty acids from fish oil have been a topic of discussion for their health effects for a number of decades. Interest in supplementation has waxed and waned as evidence emerges favoring their use, following by evidence discouraging their use or suggesting lack of effect. This whipsawing of the arguments for and against omega-3 fatty acids from fish oil has therefore left many confused and uncertain whether they should consider continuing their fish oil supplementation.

It helps to be reminded that omega-3 fatty acids, EPA and DHA, are components of food. They are not—despite what the pharmaceutical people would like you to believe—pharmaceuticals. They are not, for instance, a chemotherapy agent or antibiotic. They are oils from food. I emphasize this fact because, when it comes to components of food, we should not expect acute, dramatic effects. Instead, we should expect modest long-term benefits. Eggs, for example, are packed with beneficial nutrients like ß-carotene, vitamins D and B12, etc. that provide long-term benefits. But you wouldn’t eat eggs for a few weeks and expect dramatic health benefits. This is not to say that the benefits cannot be substantial, because they can. But benefits develop over an extended period with consistent consumption.

So let’s review the evidence that has unfolded over the last 30 years and what it tells us about omega-3 supplementation:

• Omega-3 fatty acids play an important role in reproductive health—Omega-3s, for instance, have been shown to dramatically reduce the likelihood of premature birth of a child and may reduce the likelihood of miscarriage.
   
• Omega-3 fatty acids are required for infant neurological maturation—Sadly, most women of childbearing age are miserably deficient in omega-3s due to poor diets. This means that the child developing in utero may lack sufficient quantities of omega-3s for neurological maturation. This worsens with breastfeeding, as the child extracts as much omega-3s as it can from the mother, increasing the severity of maternal omega-3 deficiency over time. Synthetic formula is no help, as the quantity of DHA (alone; no EPA) in infant formula is laughably inadequate. Omega-3 supplementation is therefore ideally undertaken during pregnancy and continued after delivery while breastfeeding. In one study, for example, mothers supplementing 2200 mg DHA and 1100 mg EPA per day (total 3300 mg per day omega-3s—a far higher dose than that used in nearly all other studies) had children who performed better on cognitive testing at age 2½ years. Other studies failed to show such benefits but relied on very low doses. The effect therefore appears to be dose-dependent, with measurable effects with higher doses ingested by the breastfeeding mother.
   
• Omega-3 fatty acids slow or prevent early cognitive decline—Recall that the brain contains large quantities of the DHA fatty acid, in particular. Evidence tells us that omega-3 supplementation, typically at higher doses, slows the deterioration of cognitive function if supplemented early in the process. Once dementia is established, there is no measurable benefit. So key is supplementation starting early in life.
   
• Omega-3s reduce cardiovascular (CV) risk—This is probably the most hotly debated issue of all. The 1999 GISSI Prevenzione Study suggested that a modest dose of EPA and DHA of 1000 mg per day reduced the incidence of cardiovascular events by 10% over 3.5 years. Several subsequent studies, however, failed to corroborate these findings, while others confirmed something similar. The JELIS study with 18,000 participants from Japan, for instance, a fish-consuming population, showed that 1800 mg of EPA alone per day reduced the incidence of CV events by 19%. Among the most persuasive evidence, however, came from the pharmaceutical industry with the REDUCE-IT study looking at 4000 mg per day (among the highest doses ever used) of EPA alone (as the modified form icosapent ethyl EPA) that reduced the incidence of CV events by 25% . Of course, in typical pharmaceutical industry fashion, they persuade prescribing physicians that there is something unique and magical in the modified form, purporting to improve how it’s done in nature, which is absurd. Analyses that compare the effects of the icosapenyl ethyl form vs. other forms such as standard ethyl ester forms in reducing triglycerides, for instance, reveal that there is no difference. But the pharmaceutical industry did us an unintentional favor by showing us that, yes, omega-3s, especially EPA, reduces the incidence of CV events when taken in higher doses. By the way, if you take EPA alone, as in the costly prescription form VASCEPA, you will have to add fish oil containing DHA if you want cognitive benefits, highlighting the absurdity of taking EPA alone in prescription form.
   
• Omega-3s reduce symptoms of autoimmune diseases—Rheumatoid arthritis is among the best studied with reduced pain and swelling, reduced number of involved joints with supplementation of ≥2000 mg EPA and DHA per day.

In short, omega-3 fatty acid supplementation does indeed provide long-term benefits across a number of health conditions. But why is there so much variation in study findings?

There are some methodological problems in studies exploring the effects of omega-3 fatty acids. Among them:

• A measure of baseline omega-3 status is rarely made—Drs. William Harris of the U.S. and Clemens von Schacky of Germany have argued that we can expect benefits from omega-3 fatty acid supplementation in study participants who begin with lower levels. We cannot expect people with higher levels at baseline to show benefit. This reduces the ability to discern treatment effects.
   
• The majority of studies use omega-3 fatty acid doses that are too low—Many studies in adults use doses <1000 mg per day. Many studies in children use doses <100 mg/day. The evolving evidence from studies using higher doses suggest that higher doses do indeed yield greater benefit. Note that the dose I advocate in my programs is 3000-3600 mg per day of combined EPA and DHA, although higher intakes are perfectly fine if you want to stack odds in favor of greater effects (as we do in people with lipoprotein (a)).
   
• Body size and percent body fat at baseline are not factored in—We know, for instance, that obese women experience half as much of a rise in blood levels of omega-3s compared to non-obese women. It means that using same dose for everyone regardless of size in a clinical trial will result in blunted or absent evidence of benefit.
   
• The form of fish oil is not specified—This is likely among the least important issues, but the ethyl ester form, while perfectly fine otherwise, requires modestly higher doses to achieve the same biological benefits as, say, the triglyceride form.

It is not uncommon to zigzag in evidence for or against something, but fish oil has received more than its fair share of uncertainties, likely due to the methodological problems listed above. It also does not help that omega-3 fatty acids are in a competitive market, causing retailers to make exaggerated or false claims that confuse people. “40 times more potent than fish oil,” or “3 times the absorption of other brands of fish oil,” or “You can’t buy this omega-3 in a health food store”—all marketing, much of it false, so don’t be persuaded by such statements.

The original IHB post is currently found on the: ⎆Infinite Health Blog, but accessing it there can require an unnecessary separate blog membership. The copy of it above is complete, and has been re-curated and enhanced for the Inner Circle membership.