Key Moments
#83 – Bill Harris, Ph.D.: Omega-3 fatty acids
Peter Attia MDKey Moments
Omega-3 fatty acids (EPA/DHA) are crucial for health, with supplements significantly impacting cardiovascular events based on dosage and individual factors.
Key Insights
Fatty acids are categorized by saturation (saturated, monounsaturated, polyunsaturated) and double bond position (omega-3, omega-6).
EPA and DHA are the primary omega-3s, essential for cell membranes and metabolism, with dietary intake often insufficient.
High doses of purified EPA (VASCEPA) demonstrated significant cardiovascular event reduction in high-risk patients, even on statins.
Arachidonic acid (omega-6) has been unfairly demonized; current research suggests linoleic acid, its precursor, may be protective against heart disease and diabetes.
Measuring omega-3 status (e.g., red blood cell EPA/DHA levels) is important for assessing intake adequacy and potential health benefits.
Supplement absorption is better with food; pharmaceutical-grade free fatty acid forms may offer absorption advantages over ethyl esters, especially when fasting.
FATTY ACID NOMENCLATURE AND STRUCTURE
The discussion begins by defining key fatty acid categories: saturated fats, which are solid at room temperature, and unsaturated fats, which are liquid. Unsaturated fats are further divided into monounsaturated (one double bond) and polyunsaturated (two or more double bonds). Polyunsaturated fats are then classified into omega-6 and omega-3 families based on the position of the first double bond relative to the omega (terminal) carbon. This distinction is crucial as it influences their chemical properties and how enzymes in the body metabolize them into various compounds.
METABOLIC PATHWAYS OF OMEGA-3 AND OMEGA-6 FATTY ACIDS
The conversion process from dietary polyunsaturated fatty acids to longer-chain, more active forms is explained. Linoleic acid (an omega-6) is converted to arachidonic acid, a vital molecule for prostaglandins and other signaling compounds. Alpha-linolenic acid (ALA), an omega-3, is converted to EPA (eicosapentaenoic acid) and then DHA (docosahexaenoic acid). While these conversions occur, the efficiency is limited, highlighting the importance of direct intake of EPA and DHA, especially for optimal health benefits.
HISTORICAL PERSPECTIVE AND EARLY RESEARCH
Dr. Bill Harris recounts his early research in 1980, investigating salmon oil's effects. This work revealed that omega-3s significantly lowered triglycerides while also observing a potential anti-platelet effect, aligning with observations in Greenland Eskimo populations. This foundational research was pivotal in recognizing the distinct cardiovascular benefits of omega-3s, particularly their impact on lipid profiles and blood clotting mechanisms, challenging existing nutritional paradigms.
CARDIOVASCULAR BENEFITS AND CLINICAL TRIALS
The conversation delves into the cardiovascular benefits, with a focus on the REDUCE-IT trial. This study showed that high-dose prescription-grade EPA (vascepa) significantly reduced cardiovascular events in statin-treated patients with elevated triglycerides. This highlights the potential of fish oil supplements, particularly EPA, to address residual cardiovascular risk beyond what statins alone can achieve, even in patients with otherwise well-controlled LDL cholesterol.
THE CONTROVERSIAL ROLE OF OMEGA-6 FATTY ACIDS
Contrary to popular belief, current research suggests omega-6 fatty acids, particularly linoleic acid, may not be detrimental and could even be protective against heart disease and diabetes. Studies show a correlation between higher linoleic acid levels and reduced disease risk. Arachidonic acid, often demonized as pro-inflammatory, also has anti-inflammatory metabolites, and its levels appear tightly regulated and not solely driven by linoleic acid intake.
OMEGA-3 INDEX AND PRACTICAL RECOMMENDATIONS
Measuring omega-3 status via the Omega-3 Index (EPA+DHA in red blood cells) is recommended, with a target range of 8-12%. This provides a more stable long-term assessment than plasma levels. While fish consumption is beneficial, supplements can effectively raise omega-3 levels. Pharmaceutical-grade products, especially free fatty acid forms, may offer absorption advantages. The focus should remain on increasing EPA and DHA intake, rather than getting overly concerned with omega-6 to omega-3 ratios.
DHA AND BRAIN HEALTH: NUANCES AND CURRENT UNDERSTANDING
DHA is recognized for its high concentration in the brain and retina, suggesting a role in cognitive and visual health. However, direct supplementation benefits for conditions like depression have not been consistently demonstrated, with EPA-rich products often showing more promise. While DHA is crucial for cell membrane structure, its precise impact on brain health and the interplay with EPA warrants further investigation, emphasizing that a balance of both is likely beneficial.
IMPACT OF DIFFERENT OMEGA-3 FORMULATIONS AND ABSORPTION
The absorption of omega-3s can be influenced by their formulation and when they are taken. Ethyl ester forms are absorbed less efficiently on an empty stomach compared to triglyceride or, more optimally, free fatty acid forms, which do not require enzymatic conversion. This distinction is particularly relevant for individuals practicing intermittent fasting or time-restricted eating, where taking supplements with meals becomes critical for maximizing absorption.
FISH OIL SUPPLEMENTS VS. WHOLE FISH CONSUMPTION
The discussion supports the idea that significant health benefits can be achieved through fish oil supplements, not solely from eating fish. While fish provides omega-3s along with other nutrients, studies like REDUCE-IT demonstrate that purified EPA can yield substantial cardiovascular benefits. This offers a viable alternative for individuals who do not consume enough fish due to taste preferences, cost, or environmental concerns.
THE FUTURE OF OMEGA-3 RESEARCH AND MEASUREMENT
Ongoing research, such as the STRENGTH trial (EPA+DHA), aims to further elucidate the benefits of omega-3s. The increasing importance of measuring omega-3 status is highlighted, with companies like OmegaQuant offering direct-to-consumer tests. Understanding one's omega-3 index is seen as a valuable tool for guiding supplementation and dietary choices, similar to monitoring cholesterol levels, to optimize long-term health outcomes. The time to see changes in red blood cell levels after dietary adjustments is approximately four months.
Mentioned in This Episode
●Supplements
●Products
●Companies
●Organizations
●Books
●Drugs & Medications
●Studies Cited
●Concepts
●People Referenced
Common Questions
Saturated fats have a long carbon chain with only single bonds and are solid at room temperature (e.g., lard, butter). Monounsaturated fats have one double bond, are liquid at room temperature but solidify in the fridge (e.g., olive oil). Polyunsaturated fats have two or more double bonds and remain liquid even in the refrigerator (e.g., fish oils, vegetable oils).
Topics
Mentioned in this video
The trade name for icosapent ethyl, a very purified EPA ethyl ester, used in the REDUCE-IT study to reduce cardiovascular events.
Another source rich in alpha-linolenic acid (ALA), an omega-3 fatty acid.
Rich in alpha-linolenic acid (ALA), an omega-3 fatty acid, beneficial for health but not an efficient source for robust EPA/DHA levels.
A dominant source of linoleic acid in the American diet, making up about 80% of dietary linoleic acid intake.
Introduced Peter Attia to Dr. Bill Harris as the go-to expert on fatty acids.
A journalist at The New York Times who wrote a story analyzing various fish oil brands for quality, content, and contaminants.
Danish investigators who conducted the Greenland Eskimo studies in the 1970s, which led to the discovery of omega-3 fatty acids.
Dr. Bill Harris's postdoc mentor in Clinical Nutrition and Lipid Metabolism at Oregon Health Sciences, who assigned him the first study on salmon oil's effect on cholesterol.
Presided over the Senate Select Committee on Health in 1977, which recommended Americans reduce saturated fat intake, influencing fat research.
Internationally recognized expert on omega-3 fatty acids, professor at Sanford School of Medicine, and President/CEO of OmegaQuant. He received five NIH grants for omega-3 research and published over 300 papers on the topic.
A 22-carbon, six-double-bond omega-3 fatty acid, important for brain and retinal health, and contributing to anti-inflammatory processes and improved platelet function.
An essential omega-6 fatty acid, primarily found in soybean and corn oil, which can be converted into arachidonic acid in the body.
An FDA-approved omega-3 drug containing 85% EPA plus DHA as ethyl esters, approved for treating very high triglyceride levels (over 500 mg/dL).
A 20-carbon, four-double-bond omega-6 fatty acid, crucial for metabolism and a precursor to prostaglandins, often misunderstood due to its association with pro-inflammatory compounds.
An essential omega-3 fatty acid found in flaxseed oil and chia seed oil, which the body can convert to EPA and DHA, though conversion efficiency is low.
A 20-carbon, five-double-bond omega-3 fatty acid, shown to be heart-healthy through multiple mechanisms, including reducing platelet stickiness and resolving inflammation.
A class of drugs that have significantly impacted residual risk for cardiovascular disease, mentioned in comparison to EPA's effects on event reduction.
An EPA-only drug approved in Japan in the late 1980s, essentially the same as Vascepa, which was successful in the JELIS trial.
A drug from AstraZeneca containing EPA plus DHA in free fatty acid form, currently being studied in the STRENGTH trial for cardiovascular outcomes.
A commercial laboratory that offers plasma phospholipid assays for omega-3 levels.
A laboratory that provides whole plasma omega-3 assays.
A reputable brand of fish oil supplements, mentioned by Peter Attia as one he typically recommends to patients.
A lab used by Peter Attia to assess mercury levels, including inorganic and organic forms, across hair, urine, and blood, to understand clearance mechanisms.
The company that manufactures Vascepa, the pure EPA drug used in the REDUCE-IT study.
A commercial laboratory that offers plasma phospholipid assays for omega-3 levels.
A company founded by Dr. Bill Harris about 10 years prior to the podcast, specializing in measuring omega-3 blood levels through a finger-stick test.
A laboratory that previously used OmegaQuant's omega-3 tests for patient panels.
A reputable brand of fish oil supplements, favored by Peter Attia for its quality and reputation.
The pharmaceutical company manufacturing Epanova, the drug used in the STRENGTH trial.
The institution from which Dr. Bill Harris earned his PhD in human nutrition.
The Food and Drug Administration, which approved omega-3 drugs for treating high triglycerides and has regulated advertising claims of fish oil products.
A prestigious medical journal that published three back-to-back omega-3 studies in May 1985, significantly raising the profile of omega-3s in the scientific community.
The institution where Dr. Bill Harris is a professor in the Department of Medicine.
Dr. Bill Harris has been the recipient of five National Institutes of Health grants for his study on omega-3 fatty acids.
The university affiliated with the Sanford School of Medicine where Dr. Bill Harris is a professor.
A clinical trial for PCSK9 inhibitors, compared to the REDUCE-IT study for its impact on cardiovascular event risk reduction.
Key research in the 1970s that revealed the high omega-3 consumption of Greenland Eskimos and their low incidence of heart attacks, helping to 'discover' omega-3s.
A landmark clinical trial that showed a 25% reduction in cardiovascular events over 5 years with 4 grams of pure EPA (Vascepa) daily in statin-treated patients with elevated triglycerides and other risk factors, with virtually no side effects.
A primary prevention study involving 20,000-25,000 relatively healthy Americans, which used 850 mg/day of EPA+DHA (one Lovaza capsule) and showed a 20% reduction in heart attacks and fatal heart attacks, particularly in those with low fish intake, despite media reports of a 'neutral' outcome.
A large ongoing clinical trial (13,000 patients) testing 4 grams total of EPA plus DHA (Epanova, as free fatty acids) with similar inclusion criteria to REDUCE-IT, expected to finish in about a year and be released at American Heart in 2020.
A Japanese omega-3 trial published in 2007 that used the EPA-only drug Epadel and showed successful outcomes.
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