AHA evidence review and another new study deem high-dose fish oil helpful in two key ways 09/02/2019
Scientific support for the heart benefits of seafood-source omega-3s just got stronger — and more specific.
Last year, the highly positive results of two well-designed clinical trials redeemed the heart-protecting reputation of fish oil, which had suffered some unwarranted dents.
Now, a positive statement from the American Heart Association (AHA) — combined with the findings of a new study — further restores the reputation of omega-3 fish oils.
First, we’ll scrutinize the recent AHA statement, which endorsed seafood-source omega-3s as powerful triglyceride-lowering allies.
Then we’ll explore a study that confirmed the minimum daily dose of omega-3 fish oil needed to yield heart-protective blood levels.
American Heart Association endorses fish oil for lowering triglycerides
Back in 2002, the American Heart Association advised people with high triglyceride levels to lower them by taking high daily doses — 2 to 4 grams (2000 to 4000 mg) — of seafood-source omega-3 fatty acids (EPA and DHA).
(It would be difficult to obtain daily EPA + DHA doses of 2 to 4 grams from eating even the fattiest fish every day, making high-potency fish oil supplements the only solution.)
Simultaneously, the US Food and Drug Administration approved use of prescription fish oils — providing either EPA+DHA or EPA alone — for lowering high triglyceride levels.
Last week, the American Heart Association (AHA) published a new advisory, based on their evidence review, which pinpointed the minimum omega-3 intakes needed to lower high triglyceride levels (Siscovick DS et al. 2019).
The new AHA advisory summarizes the latest evidence and says that daily fish oil providing 4 grams of either EPA+DHA or EPA-only can lower high triglyceride levels by 30% or more.
The AHA's scientific panel said their positive conclusion assumes that — in addition to taking high-dose fish oil — people will also make any diet and lifestyle changes needed to address the underlying causes of high triglycerides, which include obesity, diabetes, and starchy, sugary diets.
The AHA advisory did find a distinction between EPA + DHA fish oil versus EPA-only fish oil:
- Taking 4 grams of EPA alone does not raise LDL cholesterol levels.
- Taking 4 grams of EPA+DHA daily raises blood levels of LDL cholesterol slightly — unless you’re also taking a cholesterol-lowering statin drug.
That LDL-cholesterol distinction between EPA + DHA fish oil and EPA-only fish oil may not be very significant, because not all types of LDL cholesterol are harmful, and the AHA advisory didn't distinguish between types of LDL. Large, “fluffy” LDL cholesterol particles pose relatively little risk, while high levels of dense, small- and medium-size LDL promote cardiovascular disease.
One important exception is people with familial hypercholesterolemia, among whom large, light LDL-cholesterol can be a significant risk if the number of those cholesterol particles is high.
And fish oil that includes DHA appears to bring other heart benefits, such as reduced artery calcification — see Fishy Omega-3 May Keep Arteries Clear & Flexible.
Where do blood triglycerides come from?
High blood levels of triglyceride-type fats — called hypertriglyceridemia — are linked to higher risks for heart disease and its adverse outcomes, including heart attacks.
When you consume calories beyond what your body needs right away, it converts them into triglycerides and stores them in your fat cells.
And when you need energy between meals, your body uses hormones (e.g., insulin, glucagon, adrenaline) to trigger an enzyme (hormone-sensitive lipase) that makes triglycerides available to burn for energy.
Doctors will typically test for triglycerides along with cholesterol to gauge a patient's cardiovascular risk. These are the standard classifications of triglyceride levels, which can be measured as milligrams per deciliter (mg/dL) or millimoles per liter (mmol/L):
- Normal — Under 150mg/dL (1.7 mmol/L)
- Borderline high — 150-199 mg/dL (1.8 to 2.2 mmol/L)
- High — 200-499 mg/dL (2.3 to 5.6 mmol)
- Very high — 500 mg/dL (5.7 mmol/L) or higher
High triglyceride levels are fairly common in the United States, while very high triglyceride levels are less common.
Unfortunately, rates of both conditions are rising in the United States and globally, probably due to rising rates of obesity and diabetes — and due to diets high in refined starches and sugars, especially fructose, which constitutes 50% of cane sugar and 45-55% of high fructose corn syrup.
Recent omega-3 clinical trial informed the new AHA advisory
The AHA's advisory rested in part on the results of one of the biggest, best-designed clinical trials conducted to date, called REDUCE-IT.
The results of that trial, published in 2018, showed that a high-dose, EPA-only prescription fish oil (Vascepa) produced major reductions in stubbornly high blood triglyceride levels.
The REDUCE-IT trial also found that that high-dose, EPA-only prescription fish oil reduced cardiovascular deaths, heart attacks, and strokes by 25%.
And in two earlier, smaller clinical trials — called MARINE and ANCHOR — high doses (4 grams per day) of EPA-only fish oil lowered very high triglyceride levels while reducing the number of dangerous, high-density LDL cholesterol particles — a known side benefit of reducing triglyceride levels.
Another large, lengthy trial published in 2018 — called VITAL — didn't address the effects of supplemental fish oil on triglycerides, but found that people who took 1000 mg per day of a different prescription fish oil (Omacor) enjoyed these benefits:
- 28% less likely to suffer a heart attack
- 50% less likely to suffer a fatal heart attack
- 22% less likely to undergo an angioplasty procedure
AHA displays bias against non-prescription fish oil
While the new AHA advisory cited supporting evidence from trials using non-prescription fish oils, it only recommended prescription fish oils.
But, as the advisory’s authors are surely aware, the makers of almost all non-prescription fish oil supplements employ the same purification process (molecular distillation) used to produce prescription fish oils.
And it’s worth noting that in 2017, the AHA recommended supplemental fish oil — prescription or non-prescription — for “secondary” prevention of coronary heart disease (CHD), sudden cardiac death, and heart failure (Siscovick DS et al. 2017).
“Primary” prevention tactics target people with cardiovascular risk factors, while “secondary” prevention tactics target people diagnosed with coronary heart disease who are at high risk for heart attacks, stroke, heart failure, or sudden cardiac death.
The AHA's 2017 advisory didn’t recommend omega-3 fish oil for primary prevention of CHD, heart failure, or atrial fibrillation, saying that they didn’t find enough evidence to support that advice.
Study confirms fish oil dose needed for optimal heart protection
Coincidentally, a team of scientists — which included some members of the AHA triglyceride-advisory panel — just reported their findings about the optimal dose of fish oil for heart protection.
The new study was designed to determine the daily Omega-3 intakes needed to achieve an optimal “Omega-3 Index” to help protect heart health (Walker RE et al. 2019).
The international team included researchers from Harvard, Stanford, and other American and international universities. It was led by scientists from Penn State University and OmegaQuant Analytics, including the company's co-founder, William S. Harris Ph.D., who developed the Omega-3 Index.
The Omega-3 Index is the percentage of total fatty acids in red blood cell membranes accounted for by the two major omega-3s from seafood, called EPA and DHA.
Ample evidence links an Omega-3 Index of 8% or above to reduced risks for adverse cardiovascular outcomes such as heart attacks. (Given the known functions of EPA and DHA in the human body, it's very likely an Omega-3 Index of 8% or above also promotes better brain, eye, immune, developmental, and joint health.)
The study's authors analyzed data from 14 published omega-3 clinical trials involving 1,422 people, using a mathematical model to predict the impact of dietary omega-3s on the Omega-3 Index.
And they calculated that — to raise the typical Omega-3 Index of 4.9% to the minimum protective level of 8% — the average person who isn't already taking supplemental fish oil needs to consume daily fish oil providing 2000 mg of EPA + DHA.
The team estimated that it would take about 13 weeks for the average person taking 2000mg of EPA + DHA daily to achieve an Omega-3 Index of 8% — but believes that, over longer periods of time, lower daily doses would bring most people's Omega-3 Index up to the 8% goal.
An Omega-3 Index of 8% could likely also be achieved by consuming fatty fish frequently and taking a lower dose of EPA+DHA daily.
Further, the international team reported that fish oil supplements featuring omega-3s in the triglyceride form — which predominates in most fish — raised omega-3 index levels higher than supplements with ethyl-ester-form omega-3s.
The researchers also noted that — because the omega-3s in krill oil occur in the optimally absorbed phospholipid form — a daily dose of krill oil lower than 2000mg might raise people’s Omega-3 Index to 8% even more rapidly than fish oil supplements providing omega-3s in the triglyceride form.
Unfortunately, as the researchers said, 2000 mg of EPA + DHA daily is much more than would be provided by the fish intakes recommended under current U.S. and AHA guidelines, as we reported in Americans Failing to Reach Ideal Omega-3 Levels:
- The 2015–2020 Dietary Guidelines for Americans recommend 8 oz of fish per week, which would provide about 250 mg of EPA + DHA daily, or just 12.5% of the daily 2000mg required to achieve a heart-protecting Omega-3 Index.
- The American Heart Association recommends 1–2 servings of “oily” fish per week, which would provide about 500 mg of EPA+DHA daily, or just one-quarter of the daily 2000mg needed to achieve a heart-protecting Omega-3 Index.
Finally, it's important to note that the amount of omega-3s provided by fish varies quite widely.
Fatty wild fish like salmon, albacore ("white") tuna, halibut, sablefish, or sardines provide substantially higher levels than more commonly consumed lean species like skipjack (“light”) tuna, pollock (most fish sticks and sandwiches), catfish, and tilapia.
While the omega-3 levels in farmed salmon rival those in wild salmon, farmed salmon are much higher in competing omega-6 fats which — when consumed in the excess amounts typical of the standard American diet — promote heart-attacking inflammation: see Farmed Fish Possess Unhealthful Fat Profiles, Tilapia Taken to Task, and the Omega-3/6 Balance page of our website.
- Backes J, Anzalone D, Hilleman D, Catini J. The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia. Lipids Health Dis. 2016 Jul 22;15(1):118. doi: 10.1186/s12944-016-0286-4. Review.
- Handelsman Y, Shapiro MD. Triglycerides, Atherosclerosis, and Cardiovascular Outcome Studies: Focus on Omega-three Fatty Acids. Endocr Pract. 2017 Jan;23(1):100-112. doi: 10.4158/EP161445.RA. Epub 2016 Nov 7. Review.
- Oscarsson J, Hurt-Camejo E. Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their mechanisms of action on apolipoprotein B-containing lipoproteins in humans: a review. Lipids Health Dis. 2017 Aug 10;16(1):149. doi: 10.1186/s12944-017-0541-3. Review.
- Singh S, Arora RR, Singh M, Khosla S. Eicosapentaenoic Acid Versus Docosahexaenoic Acid as Options for Vascular Risk Prevention: A Fish Story. Am J Ther. 2016 May-Jun;23(3):e905-10. doi: 10.1097/MJT.0000000000000165. Review.
- Siscovick DS et al. Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association. Circulation. 2017 Apr 11;135(15):e867-e884. doi: 10.1161/CIR.0000000000000482. Epub 2017 Mar 13. Review.
- Skulas-Ray AC, Wilson PWF, Harris WS et al. Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association. Circulation. 2019 Aug 19:CIR0000000000000709. doi: 10.1161/CIR.0000000000000709. [Epub ahead of print]
- Walker RE, Jackson KH, Tintle NL, Shearer GC, Bernasconi A, Masson S, Latini R, Heydari B, Kwong RY, Flock M, Kris-Etherton PM, Hedengran A, Carney RM, Skulas-Ray A, Gidding SS, Dewell A, Gardner CD, Grenon SM, Sarter B, Newman JW, Pedersen TL, Larson MK, Harris WS. Predicting the effects of supplemental EPA and DHA on the omega-3 index. Am J Clin Nutr. 2019 Aug 8. pii: nqz161. doi: 10.1093/ajcn/nqz161. [Epub ahead of print]